Antigeno Prostatico Especifico: inutil para el cribado de cancer de prostata


Todavia desconozco en que idioma hay que escribir esto, pero por enesima  vez sale otro articulo que dice que la PSA,  no tiene ninguna utilidad en el cribado de cáncer de próstata y que sólo sirve para el seguimiento de pacientes con Cáncer de prostata. El tema es simple. Se trata de una prueba inespecifica, y el famoso antigeno es volumen-dependiente del tamaño de la prostata. Por ende, en la natural evolucion que tenemos los hombres la prostata se agranda con la edad. Por tanto, ningun valor sirve para diferenciar si ese agrandamiento se  debió a la hipertrofia prostática benigna, que también es muy común luego de los 65 años. Por otro lado, un viejo anatomista,  Testut, ya escribia en su tratado que data del año 1900, que en sus autopsias encontraba un 100% de cáncer de prostata en hombres  mayores de 80 años. En otras palabras, y aunque los urólogos se empeñen en poner al cancer de próstata como un grave problema de salud, colocandolo entre las primeras causas de muerte, la realidad indica, que nos morimos más con cáncer de próstata que por el cáncer mismo. Por ende es un buen marcador de la evolución del cáncer pero no tiene ninguna utilidad, escrito en Inglés (también ha sido escrito en castellano, catalán, portugues, francés, ruso, y seguramente en esperanto) por el  British Medical Journal.
Por ende tendremos que seguir lidiando con los expertos que aparecen en la prensa de todo el mundo, e intentan convencer a la gente de hacerse estos estudios desde los 50 años.

Utilizando una cohorte grande Seuca relacionada con un registro nacional de cáncer, los investigadores compararon los valores iniciales de PSA de aquellos que desarrollaron cáncer de próstata en el curso de 7 años post escrutinio, con otros hombres de similares características que no desarrollaron cáncer de próstata. La sobreposición de los valores de PSA frustraron los esfuerzos de los investigadores de encontrar un valor que tenga alta especificidad así como una sensibilidad del 50%. Sin embargo, notaron que un valor de PSA menor de 1 ng/mL virtualmente descarta el diagnóstico durante el período de seguimiento.

Debido a los resultados de este estudio, se podría decir que los datos sobre los costos y beneficios de las pruebas de PSA permanecen insuficientes para apoyar el escrutinio masivo.

Referencia: Benny Holmström, et al. Prostate specific antigen for early detection of prostate cancer: longitudinal study. BMJ. Septiembre 2009;339:b3537.

Frecuencia del cancer en Argentina


Las estadisticas siguen ubicando al cancer de mama en mujeres, y al cancer de prostata en hombres, como las mas frecuentes causas de mortalidad. Seria interesante conocer, como sabemos de otros paises a que edad aparecen este tipo de neoplasias. Sin duda ambos son frecuentes, pero como siempre hemos dicho, en una poblacion mas bien envjecida como la Argentina, los que mueren por cancer de prostata  posiblemente mueran mas por su tratamiento, y mueran con el cancer y no por el cancer. La cantidad de articulos que hemos publicado al respecto es abrumadora. En cuanto al cancer de mama es otro de los canceres cuyo screening sistematico se discute en todo el mundo. La mamografia disminuye un 33% la mortalidad, claro que este numero se refiere a numeros relativos, cuando hablamos de numeros absolutos la mortalidad solo se reduce de un 3% a un 2%, mientras que la disminuciòn de este tipo de cancer con tratamientos como la terapia de reemplazo hormonal, que estaria contraindicada segun el estudio WHI, bajaria en un 15% la incidencia de Cancer de mama. Relativo vs. absoluto. Pero la prensa se empeña en seguir con el marketing del miedo. 

Los cánceres más frecuentes en el país

  • El cáncer de pulmón y el de colon pueden prevenirse si se adoptan hábitos saludables.
  • El cáncer de pulmón y el de colon pueden prevenirse si se adoptan hábitos saludables.
Por: Celina Abud
Los factores ambientales son los que más influyen en los nuevos casos de cáncer, según señalaron expertos en coincidencia con el día mundial de la lucha contra esta enfermedad, que se celebra el 4 de febrero. En ese sentido, no es casualidad que el escenario del país frente a esta patología cambie ampliamente entre provincias. Existen muchas variantes relacionadas a la pobreza, aunque también los expertos advierten que hay otras más típicas de las clases medias y altas. Incluso, son muchos los tumores relacionados a la vida moderna.
La Agencia Internacional de Investigaciones en Cáncer (IARC, por sus siglas en inglés), en base a datos enviados por distintos organismos del país, estimó que en 2008 hubo 104.859 nuevos casos en Argentina. En la población adulta, los más frecuentes fueron el de mama en mujeres y el de próstata en hombres; seguidos por el colorrectal y el de pulmón en ambos sexos.
Al respecto, el Dr. Mario Bruno, Jefe Honorario del Servicio de Oncología del Hospital Álvarez,  advirtió a este medio sobre un crecimiento de nuevos casos de cáncer de mama en el país debido a que las mujeres hoy postergan la maternidad. “Esta enfermedad está estrechamente relacionada con los estrógenos, una hormona que casi no está presente durante el embarazo. Cuando se posterga la decisión de ser madre, la glándula mamaria recibe esta hormona ininterrumpidamente durante 20 años o más, desde la primera menstruación. Por eso, la patología afecta más a las clases medias y altas que a las más bajas, que tienen más hijos y a edades más precoces”, indicó.
A pesar de la alta incidencia de estos tumores entre mujeres, Graciela Abriata, coordinarora del Sistema de Vigilancia y Análisis Epidemiológico del Instituto Nacional del Cáncer (INC), indicó que la mortalidad por esta afección disminuyó gracias a la detección temprana, al igual que los decesos por cáncer de ovario y útero.
En el otro extremo, existen cánceres relacionados a la pobreza y la vulnerabilidad social como el de cuello uterino. Esto sucede por la falta de acceso de las mujeres a los exámenes ginecológicos como el papanicolau o la colposcopía y revertir esta situación es un objetivo prioritario anunciado por la cartera sanitaria nacional.
Con respecto al cáncer colorrectalAbriata dijo a DocSalud.com que entre el período entre 1997 y 2009 “hubo un sutil aumento en las tendencias de mortalidad” por esta afección y también por cáncer de páncreas en ambos sexos. En ese sentido, Bruno indicó que los alimentos que utilizan conservantes en base a nitratos y nitritos aumentan las chances de adquirir la enfermedad en el colon.
Por otra parte, subieron los decesos femeninos por cáncer de pulmón, mientras que se redujeron los fallecimientos por esta causa en el sexo masculino. “Esta tendencia se debe, probablemente, a que los hombres estén fumando menos”, indicó Abriata, quien también recordó que el tabaco es clave en el desarrollo del cáncer de vejiga y laringe.
Prevención y detección temprana
Algunos cánceres, como el de piel pueden prevenirse. Sin embargo, la Dra. Guadalupe Pallota, perteneciente a la Asociación Argentina de Oncología Clínica (AAOC) remarcó a este medio que en la actualidad “existe una epidemia de melanoma, relacionado con el hábito de tomar sol”.  Pero aclaró que “si bien subió la incidencia, es decir, los casos nuevos, no aumentó la mortalidad por esta causa ya que la población consulta mucho al dermatólogo”.
Es que, efectivamente, muchos tumores pueden prevenirse al adoptar conductas más saludables, como no fumar o exponerse al humo de tabaco; realizar ejercicio o comer más frutas y verduras. Otros, provocados por virus como el hepatocarcinoma (relacionado con el agente de la hepatitis B) o el de cuello uterino (asociado al virus del papiloma humano  o VPH) pueden disminuir gracias a la aplicación de vacunas.
Pero en otros casos, donde no se puede evitar la aparición de la enfermedad, la detección precoz cambia sustancialmente el pronóstico y algunas variantes como la de mama, diagnosticada a tiempo, tienen altas tasas de curación.
“Los chequeos anuales son importantes, aunque también los exámenes dependen del riesgo personal de cada individuo, por lo que siempre deben estar indicados por un especialista”, indicó Abriata.
Es que si bien en la población general se  recomienda una colonoscopía o videocolonoscopía a los mayores de 50 años, “a los que tienen antecedentes familiares se le sugiere practicarse este estudio cinco años antes del diagnóstico de la enfermedad en el pariente más joven”, explicó Pallota. Para las mujeres, la mamografía, la ecografía mamaria y el papanicolau son exámenes que el ginecólogo debe indicar una vez al año.
Por último, la especialista relató que desde 2010 se aprobaron las tomografías de baja radiación para detectar tumores en el pulmón, pero como el método es bastante novedoso todavía existe cierto margen de error y se corre el riesgo de que se extraigan protuberancias no cancerígenas.

El panorama infantil

De acuerdo a la información del Registro Oncopediátrico Hospitalario Argentino (ROHA) hasta el año 2009, las leucemias representan la patología oncológica más prevalente en los menores de 15 años.
Es que los niños suelen ser víctimas ante los cánceres más difíciles de prevenir, ya sea por ser de rápida propagación, como las leucemias o los linfomas (que, en algunos casos pueden ser desencadenados por una respuesta anormal ante el virus Epstein Barr) o aquellos que son puramente hereditarios, donde inciden más los factores genéticos que los ambientales, por ejemplo el retinoblastoma, en el área ocular.
Para el diagnóstico oportuno del cáncer en esta población, el ROHA diseño la publicación “Cuando sospechar cáncer en el niño”, una guía de uso clínico difundida actualmente por el INC en todos los centros de atención pediátrica en el país.

Los números que se vienen

La generación de estadísticas sobre la problemática del cáncer en el país es un “objetivo inmediato” para el Ministerio de Salud, según se informó en un comunicado. Por eso, Javier Osantik, integrante del Consejo de Dirección del INC, dijo que “informar es una prioridad”, por lo que la entidad a la que pertenece “acompaña todas las estrategias de prevención y elabora material informativo para ponerlo al alcance de la población y del cuerpo médico de todo el sistema sanitario argentino”.  A su vez, indicó que “a mediano y largo plazo, por ejemplo, de 10 a 15 años, se va a tener un panorama global a nivel país con estimativos reales en materia de mortalidad por cáncer”.
Por su parte, Abriata explicó que desde el área de Coordinación de Vigilancia Epidemiológica y Reporte (SIVER – INC) se ha desarrollado el Registro Institucional de Tumores de Argentina (RITA), que en la actualidad esta en prueba piloto. Esta búsqueda de base hospitalaria está orientada a la recolección de datos sobre la ocurrencia de casos, los circuitos de atención  y los resultados del sistema de salud en todo el país. 

Occult papillary carcinoma of the thyroid. A "normal" finding in Finland. A systematic autopsy study.


Papillary Carcinoma of the Thyroid This illust...Image via Wikipedia

Cancer. 1985 Aug 1;56(3):531-8.

Occult papillary carcinoma of the thyroid. A “normal” finding in Finland. A systematic autopsy study.

Abstract

The thyroids from 101 consecutive autopsies from Finland were subserially sectioned at 2- to 3-mm intervals. From 36 thyroids, 52 foci of occult papillary carcinoma (OPC) were found, giving a prevalence rate of 35.6%, the highest reported rate in the world. The rate was higher, although not significantly, in males (43.3%) than in females (27.1%), but it did not correlate to the age of the patients. Twenty-six glands contained one tumor focus and ten glands contained two to five tumor foci. Only a minority of the smallest tumors can be detected with the method used. The probable number of OPCs over 0.15 mm in diameter was calculated to be about 300 in this material. The tumor diameter varied from 0.15 mm to 14.0 mm, with 67% of tumors under 1.0 mm. The smallest tumors were usually circumscribed and were composed almost solely of follicles. Larger tumors had more papillary structures and were often invasive. Fibrosis and, in the largest OPCs, lymphocytic reaction were seen around the invasive islands. All tumors were positively stained for thyroglobulin and all but one of the tumors stained positively for epidermal keratin. OPC appears to arise from follicular cells of normal follicles. Apparently the great majority of the tumors remain small and circumscribed and even from those few tumors that grow larger and become invasive OPCs only a minimal proportion will ever become a clinical carcinoma. According to the study, OPC can be regarded as a normal finding which should not be treated when incidentally found. In order to avoid unnecessary operations it is suggested that incidentally found small OPCs (less than 5 mm in diameter) were called occult papillary tumor instead of carcinoma.

PMID:

 

2408737

 

[PubMed – indexed for MEDLINE]

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Guidelines for Breast Cancer


1991http://www.scribd.com/embeds/74045393/content?start_page=1&view_mode=list&access_key=key-1pnqsdg4nlltoxtc0d71(function() { var scribd = document.createElement(“script”); scribd.type = “text/javascript”; scribd.async = true; scribd.src = “http://www.scribd.com/javascripts/embed_code/inject.js”; var s = document.getElementsByTagName(“script”)[0]; s.parentNode.insertBefore(scribd, s); })();


Juan GérvasImage via Wikipedia

Tres palabras

En su análisis de situación, Juan Gérvas se manifiesta en contra de las mamografías, de cuya promoción comienzan a multiplicarse los ejemplos en las Comunidades Autónomas. A juicio del comentarista, y teniendo en cuenta los datos de los resultados, los efectos negativos superan a los positivos.Con muy pocas palabras se pueden transmitir sentimientos que cambien profundamente nuestras vidas; por ejemplo, con 2 palabras: te quiero.


Con Cuatro palabras canta Antonio Machín:
….
Voy a decirte la verdad desnuda,
aunque comprendo que vas a sufrir
….
Mírame bien y escucha de mis labios
cuatro palabras que son mi razón:
Ya no te quiero.
Ya no te quiero.
Olvídame y adiós.


Son palabras crueles, pero peor es la simulación y el engaño. Quizá por ello aquel la verdad os hará libres, que escribió Pablo de Tarso en una de sus Epístolas.


Sin embargo, hay otro bolero que pide justamente lo contrario, de Víctor Iturbe:
….
Sé que tu cariño no es sincero.
Sé que mientes al besar.
Y mientes al decir te quiero.
Mas si das a mi vivir la dicha con tu amor fingido
miénteme una eternidad
que me hace tu maldad feliz.
¿Y qué más da?
La vida es una mentira.
….


Son las ambivalencias que pueblan nuestras vidas, el deseo simultáneo de saber y de no saber. El deseo de enfrentarnos a la verdad y de ignorarla. Es lógico, pues nuestros sentimientos son complejos. No es ni un si ni un no, pues estamos llenos de peros. Es lo característico de nuestra especie.


Los médicos nos enfrentamos a esa complejidad en lo que respecta al enfermar. El malestar se refiere a todas las áreas de la vida, y por ello nos atañe un poco todo, pero sólo cuando el malestar se transforma en alteración que dificulta la vida normal. La enfermedad se vive de forma distinta según la cultura y la situación social. Por ejemplo, no es lo mismo una diabetes infantil en una familia bien estructurada que en un niño de la misma edad y sexo con diabetes infantil en una familia desestructurada y pobre.


El enfermar no se puede entender sin verlo integrado en la sociedad. Por ejemplo, en Japón se muere mucho de ictus, básicamente hemorragia cerebral, pero tanto porque allí es frecuente como porque en Japón esa es una muerte honorable. Pasa lo mismo, pero al revés, en España, donde las cifras de muertes por suicidio son falsas, casi la cuarta parte de las reales, pues es causa de muerte indigna. Tanto en Japón como en España se miente, incluso en los certificados médicos. Se miente respecto a palabras y expresiones con gran fuerza, como suicidio.


A veces se miente por interés.


Cribado (screening)


Es cribado el servicio de salud pública por el cual se ofrecen a una población definida sin síntomas (con mayor riesgo o afectación por una enfermedad) determinadas pruebas que permiten identificar a los individuos con mayor probabilidad de obtener más beneficio que perjuicio por dichas pruebas y los tratamientos consiguientes.


De la definición se deduce que todo cribado causa daños, y que sólo algunos participantes obtendrán más beneficios que daños. En un lema en 13 palabras “Todos los cribados producen daños; en algunas personas producen más beneficios que daños”.


Los 10 criterios que dan fundamento a la existencia de los cribados los fijaron en 1968 Wilson y Joungner, en una publicación de la OMS, Ginebra (Public Health Paper, 34). Son:


1/ el problema debe ser importante para la salud pública
2/ existe tratamiento para los pacientes con el problema de salud
3/ hay instalaciones para confirmar los resultados del cribado, y para el tratamiento consiguiente
4/ existe una fase pre-sintomática o latente
5/ se cuenta con una prueba de detección precoz
6/ dicha prueba es aceptable para la población
7/ se conoce la historia natural de la enfermedad
8/ hay acuerdo sobre a quién tratar como enfermo
9/ el coste de la detección y tratamiento precoz debe ser proporcional a los costes globales y
10/ la detección de casos será un proceso continuo.


Con estos criterios todas las pruebas de cribado del cáncer deberían anularse, pues no los cumplen, especialmente respecto a la historia natural de la enfermedad.


Pero nos mienten, y nos dicen en 5 palabras aquello de más vale prevenir que curar.


A veces se miente por interés.


Cribados y mujer


El primer cribado del cáncer se implantó en las mujeres, y sin ningún fundamento científico. Fue el del cáncer de cuello de útero, que tiene más de 60 años de historia y nunca ha sido evaluado con criterios de ensayo clínico. Así persiste y da de comer a muchos ginecólogos. Por ejemplo, en 10.000 mujeres de 30 a 65 años, con tres o más citologías consecutivas normales, ninguna tendrá cáncer de cuello de útero (aunque en 5 se podrá diagnosticar una displasia). Pues bien, con el Papanicolau clásico (sensibilidad 69% y especificidad 97%), 303 darán resultado anormal, lo que da un valor predictivo del 1% (en 298 habrá sido un error). Es, casi, el valor predictivo de una pitonisa.


Pero otros métodos, con menos rendimiento (sensibilidad 84%, especificidad 88%) conllevan un menor valor predictivo, del 0,3% (1.204 resultados anormales, de los que 1.199 serán errores). Es un valor predictivo por debajo del de la pitonisa.


La Comunidad de Madrid ha estado difundiendo el cribado del cáncer de mama entre mujeres de 50 a 65 años, con un mensaje simple, en 4 palabras, la mamografía salva vidas. El Gobierno Vasco ha decidido ofrecer el cribado con mamografía para el cáncer de mama a todas las mujeres de 40 a 49 años con algún familiar con antecedente de tal cáncer. Para no quedarse atrás, en la Comunidad de Castilla-La Mancha quieren hacer mamografías a todas las mujeres, y su Presidenta, María Dolores Cospedal, de 45 años, se hizo su correspondiente mamografía para promover el cribado.


Son curiosas y contra la ciencia todas estas decisiones. A veces se nos miente por interés. El cribado del cáncer de mama no salva ninguna vida. El cribado del cáncer de mama, en las mejores condiciones, en mujeres de 40 a 74 años, cambia la probabilidad de no morir de cáncer de mama del 99,39 al 99,59%. Y entre las mujeres sometidas al cribado aumentan las muertes por otras causas, de forma que el balance final es nulo en muertes, y pesado en la carga de morbilidad en las mujeres con falsos positivos, falsos negativos y en las intervenidas, por la mutilación, la ansiedad, el miedo, la disminución de auto-imagen, cambios sutiles en la vida diaria y otros.


La mortalidad por cáncer de mama, antes de la implantación del cribado, ha estado disminuyendo en España a un ritmo de 1,4% anual. No sabemos por qué. Ahora se apunta ese tanto el cribado del cáncer de mama.


Asustan con el cáncer de mama, cada día más frecuente. Pero su frecuencia es artificial. Por ejemplo, en Cataluña hasta un 40% de las mamas extirpadas con cáncer de mama no tenían verdadero cáncer de mama (cáncer con crecimiento sin control y metástasis). Por ejemplo, en Castilla-León el cribado adelanta el diagnóstico de 1 cáncer de cada 7, indolente y no agresivo, al coste de retrasar (por los falsos negativos) 1 cáncer de cada 9 agresivos y con metástasis.


El sobre-diagnóstico de cáncer de mama por el cribado con mamografía conlleva mortalidad y sufrimiento, por la cirugía con anestesia, la radioterapia, la quimioterapia y demás.


El cribado no disminuye la mortalidad global, pues lo que evita de muertes por cáncer de mama lo incrementa por muertes por sobre-diagnóstico.


Es decir, en 3 palabras, la mamografía mata.


Repito, el sobre-diagnóstico conlleva muertes en el cribado de cáncer de mama. En 3 palabras, la mamografía mata.


Hay que salvar las mamas y rechazar el cribado para, en 3 palabras, disfrutar la vida.


Juan Gérvas (jgervasc@meditex.es) es médico general y promotor del Equipo CESCA (www.equipocesca.org)

Contraceptive pill associated with increased prostate cancer risk worldwide


Age-standardised death rates from Prostate can...Image via Wikipedia

ABSTRACT
Background: Several recent studies have suggested that oestrogen exposure may increase the risk of prostate cancer (PCa).
Objectives: To examine associations between PCa incidence and mortality and population-based use of oral contraceptives (OCs). It was hypothesised that OC by-products may cause environmental contamination, leading to an increased low level oestrogen exposure and therefore higher PCa incidence and mortality.
Methods: The hypothesis was tested in an ecological study. Data from the International Agency for Research on Cancer were used to retrieve age-standardised rates of prostate cancer in 2007, and data from the United Nations World Contraceptive Use 2007 report were used to retrieve data on contraceptive use. A Pearson correlation and multivariable linear regression were used to associate the percentage of women using OCs,intrauterine devices, condoms or vaginal barriers to the age standardised prostate cancer incidence and mortality. These analyses were performed by individual nations and by continents worldwide.
Results: OC use was significantly associated with prostate cancer incidence and mortality in the individual nations worldwide (r¼0.61 and r¼0.53, respectively; p<0.05 for all). PCa incidence was also associated with OC use in Europe (r¼0.545, p<0.05) and by continent (r¼0.522, p<0.05). All other forms of contraceptives (ie, intra-uterine devices, condoms or vaginal barriers) were not correlated with prostate cancer incidence or mortality. On multivariable analysis the correlation with OC was independent of a nation’s wealth. Conclusion: A significant association between OCs and PCa has been shown. It is hypothesised that the OC effect may be mediated through environmental oestrogen levels; this novel concept is worth further ……. Risk Factor Oral Contraceptive Prostate Cancerhttp://www.scribd.com/embeds/72841348/content?start_page=1&view_mode=list&access_key=key-2l5oid9gttp9s328jdpz(function() { var scribd = document.createElement(“script”); scribd.type = “text/javascript”; scribd.async = true; scribd.src = “http://www.scribd.com/javascripts/embed_code/inject.js&#8221;; var s = document.getElementsByTagName(“script”)[0]; s.parentNode.insertBefore(scribd, s); })();

British breast cancer screening now under independent review


Normal (left) versus cancerous (right) mammogr...Image via Wikipedia

Source: Health News Review

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Questions about how best to communicate to the public about the tradeoffs of potential benefits versus potential harms of mammography do not end at America‘s shores.

An independent investigation into breast cancer screening has been set up by the government’s cancer chief to try to settle the growing controversy around its usefulness and potential harms.

Prof Sir Mike Richards‘s move is an attempt to put to rest the criticisms of a number of scientists, who say the NHS (British National Health Service) screening programme wrongly identifies cancers that might never harm women, leading to unnecessary and potentially damaging treatment with surgery, drugs and radiation therapy.
They also contest the official NHS position, which is that although there is some over-treatment as a result of screening, mammograms save lives.
The BMJ today published a letter from Susan Bewley, professor of complex obstetrics, Division of Women’s Health, King’s College London, to the man BMJ calls “England’s cancer tsar,” Mike Richards. Excerpt of her letter: 

“I declined screening when it was offered, as the NHS breast screening programme was not telling the whole truth. As a non-expert in the subject, I found myself examining the evidence for breast screening with increasing doubts. I compared the NHS and Nordic Cochrane Centre leaflets and found that the NHS leaflets exaggerated benefits and did not spell out the risks. Journals showed a reputable and growing body of international opinion acknowledging that breast cancer screening was not as good as used to be thought. The distress of overdiagnosis and decision making when finding lesions that might (or might not) be cancer that might (or might not) require mutilating surgery is increasingly being exposed. The oft repeated statement that “1400 lives a year are saved” has not been subjected to proper scrutiny. Even cancer charities use lower estimates. I expressed my misgivings to you “behind the scenes” as a work colleague. You replied in a personal email “that the large majority of experts in this country disagrees with the methodology used in the Cochrane Centre reviews of breast screening.”

It is extraordinary to be told that methodology is contentious so many years into the national programme.”

“I take the current controversy very seriously. I will do my best to achieve consensus on the evidence, though I realise this may not ultimately be possible. Should the independent review conclude that the balance of harms outweighs the benefits of breast screening, I will have no hesitation in referring the findings to the UK National Screening Committee and then ministers. You also have my assurance that I am fully committed to the public being given information in a format that they find acceptable and understandable and that enables them to make truly informed choices.”

Most women with screen-detected breast cancer have not had their life saved by screening


Age-standardised death rates from Breast cance...Image via Wikipedia

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That’s the conclusion of an article published today in the Archives of Internal Medicine. I’m on the run today, but here’s the abstract


Background Perhaps the most persuasive messages promoting screening mammography come from women who argue that the test “saved my life.” Because other possibilities exist, we sought to determine how often lives were actually saved by mammography screening.

Methods We created a simple method to estimate the probability that a woman with screen-detected breast cancer has had her life saved because of screening. We used DevCan, the National Cancer Institute‘s software for analyzing Surveillance Epidemiology and End Results (SEER) data, to estimate the 10-year risk of diagnosis and the 20-year risk of death–a time horizon long enough to capture the downstream benefits of screening. Using a range of estimates on the ability of screening mammography to reduce breast cancer mortality (relative risk reduction [RRR], 5%-25%), we estimated the risk of dying from breast cancer in the presence and absence of mammography in women of various ages (ages 40, 50, 60, and 70 years).
Results We found that for a 50-year-old woman, the estimated risk of having a screen-detected breast cancer in the next 10 years is 1910 per 100 000. Her observed 20-year risk of breast cancer death is 990 per 100 000. Assuming that mammography has already reduced this risk by 20%, the risk of death in the absence of screening would be 1240 per 100 000, which suggests that the mortality benefit accrued to 250 per 100 000. Thus, the probability that a woman with screen-detected breast cancer avoids a breast cancer death because of mammography is 13% (250/1910). This number falls to 3% if screening mammography reduces breast cancer mortality by 5%. Similar analyses of women of different ages all yield probability estimates below 25%.
Conclusions Most women with screen-detected breast cancer have not had their life saved by screening. They are instead either diagnosed early (with no effect on their mortality) or overdiagnosed.

PSA and prostate cancer


This figure shows the heterogeneity of cancer ...Image via Wikipedia

Draft Recommendation Statement


The U.S. Preventive Services Task Force will be accepting comments on this draft recommendation statement beginning on Tuesday, October 11, 2011.
The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific clinical preventive services for patients without related signs or symptoms.
It bases its recommendations on the evidence of both the benefits and harms of the service, and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.
The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.

Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement
DRAFT

Summary of Recommendation and Evidence

The U.S. Preventive Services Task Force (USPSTF) recommends against prostate-specific antigen (PSA)-based screening for prostate cancer.This is a grade D recommendation.
This recommendation applies to men in the U.S. population that do not have symptoms that are highly suspicious for prostate cancer, regardless of age, race, or family history. The Task Force did not evaluate the use of the PSA test as part of a diagnostic strategy in men with symptoms that are highly suspicious for prostate cancer. This recommendation also does not consider the use of the PSA test for surveillance after diagnosis and/or treatment of prostate cancer.

Rationale

Importance

Prostate cancer is the most commonly diagnosed nonskin cancer in men in the United States, with a lifetime risk of diagnosis currently estimated at 15.9%. Most cases of prostate cancer have a good prognosis, but some are aggressive; the lifetime risk of dying from prostate cancer is 2.8%. Prostate cancer is rare before age 50 years and very few men die of prostate cancer before age 60 years. The majority of deaths due to prostate cancer occur after age 75 years (1).

Detection

Contemporary recommendations for prostate cancer screening all incorporate the measurement of serum PSA levels; other methods of detection such as digital rectal examination or ultrasonography may be included. The evidence is convincing that PSA-based screening programs result in the detection of many cases of asymptomatic prostate cancer. The evidence is also convincing that the majority of men who have asymptomatic cancer detected by PSA screening have a tumor that meets histological criteria for prostate cancer, but the tumor either will not progress or is so indolent and slow-growing that it will not affect the man’s lifespan or cause adverse health effects, as he will die of another cause first. The terms “overdiagnosis” or “pseudodisease” are used to describe both of these situations. It is difficult to determine the precise magnitude of overdiagnosis associated with any screening and treatment program. The rate of overdiagnosis of prostate cancer increases as the number of men subjected to biopsy increases. The number of cancer cases that could be detected in a screened population is large; a single study in which men eligible for PSA screening underwent biopsy irrespective of PSA level detected cancer in nearly 25% of men (2). The rate of overdiagnosis will also depend upon the age at which diagnosis is made. Cancer diagnosis in older men with shorter life expectancies is much more likely to be overdiagnosis.

Benefits of Detection and Early Intervention

The primary goal of prostate cancer screening is to reduce deaths due to prostate cancer, and a reduction in either prostate cancer death or overall mortality was the primary outcome addressed in all prostate cancer screening studies assessed by the Task Force. The evidence is convincing that for men aged 70 years and older, screening has no mortality benefit. For men aged 50 to 69 years, the evidence is convincing that the reduction in prostate cancer mortality 10 years after screening is small to none. Screen-detected cancer can fall into one of three categories: cancer that results in death in spite of early diagnosis and treatment, cancer for which early diagnosis and treatment improves survival, and cancer for which the outcome would be good in the absence of screening due to indolent tumors. Ninety-five percent of men with PSA-detected cancer who are followed for 12 years do not die from that cancer, even in the absence of definitive treatment (3). The possibility is very small that death from prostate cancer is less likely in men whose prostate cancer is detected by PSA screening rather than waiting for clinical detection, and the time to any potential benefit is long. No prostate cancer screening study, individually or combined with other screening studies, or study of treatment of screen-detected cancer, has demonstrated a reduction in all-cause mortality.

Harms of Detection and Early Intervention

Harms related to screening. Convincing evidence demonstrates that the PSA test often produces false-positive results (approximately 80% of positive PSA tests are false positives when a cut-off point of 2.5–4.0 ng/mL is used) (4). The evidence is adequate that false-positive PSA tests are associated with negative psychological effects, including a persistent worry about prostate cancer. Men that have a false-positive test are more likely to have additional testing, including biopsies, in the following year than those who have a negative test (5). Over a 10-year period, approximately 15%–20% of men will have an abnormal result that triggers a biopsy, depending upon the PSA threshold and testing interval used (4). The evidence is convincing that prostate biopsy causes fever, infection, bleeding, and transient urinary difficulty in some men (about 68 events per 10,000 biopsies), as well as pain (67).
The evidence is also convincing that PSA-based screening leads to substantial overdiagnosis of prostate tumors. As noted above, overdiagnosis occurs when, despite a tumor’s pathological characteristics, it does not progress to cause illness or death in a man’s lifetime. Overdiagnosis is of particular concern in prostate cancer because a high percentage of men are treated at the time of diagnosis, and a man with an indolent lesion may experience any of the associated harms of a therapy but cannot benefit, by the very nature of the condition, from that intervention.
The USPSTF considered the magnitude of these screening-associated harms to be at least small.
Harms related to treatment of screen-detected cancer. Adequate evidence shows that nearly 90% of men with PSA-detected prostate cancer undergo early treatment with surgery, radiation, or androgen deprivation therapy. Adequate evidence also shows that up to 5 in 1,000 men will die within 1 month of prostate cancer surgery and between 10 and 70 men will have serious complications but survive. Radiotherapy and surgery result in adverse effects, including urinary incontinence and erectile dysfunction in at least 200 to 300 of 1,000 men treated with these therapies. Radiotherapy is also associated with bowel dysfunction (68).
Some clinicians have utilized androgen deprivation therapy for early-stage prostate cancer, particularly in older men, despite the fact that this is not an U.S. Food and Drug Administration (FDA)-approved indication and it has not been shown to improve clinical outcomes in localized prostate cancer. Adequate evidence shows that androgen deprivation therapy for localized prostate cancer is associated with erectile dysfunction (in about 400 out of 1,000 men treated), as well as gynecomastia and hot flashes. In addition, in patients given androgen deprivation therapy for advanced prostate cancer, some evidence suggests an increased risk of other serious harms, such as myocardial infarction and coronary heart disease, diabetes, and fractures, although these harms have not been well studied in men treated for localized prostate cancer (68).
PSA-based screening for prostate cancer results in the diagnosis and treatment of many more cancer cases than would occur without screening; thus, screening results in many more men who are subject to treatment-related adverse events. A sizable proportion of the additional cancer cases that are detected with screening represent overdiagnosis. Overdiagnosed men cannot reap benefit from the intervention, but are subject to all of the related risks of surgery, radiation, or hormone therapy. As such, overtreatment represents a critical consequence of PSA-based screening as currently utilized, most notably in the context of a high propensity for physicians and patients to elect to treat most cases of screen-detected cancer. Even for those men whose screen-detected cancer would otherwise have been later identified symptomatically, a high proportion experience the same outcome, and are thus subjected to the harms of treatment for a much longer period of time (39). The evidence is convincing that PSA-based screening for prostate cancer results in considerable overtreatment.
The USPSTF considered the magnitude of these treatment-associated harms to be at least moderate.

USPSTF Assessment

The common perception that PSA-based early detection of prostate cancer prolongs lives is not supported by the scientific evidence. The findings of the two largest trials highlight the uncertainty that remains about the precise effect that screening may have, and demonstrate that if any benefit does exist, it is very small after 10 years. The European trial found a statistically insignificant 0.06% absolute reduction in prostate cancer deaths for men aged 50 to 74 years, while the U.S. trial found a statistically insignificant 0.03% absolute increase in prostate cancer deaths (67). A meta-analysis of all published trials found no statistically significant reduction in prostate cancer deaths (10). At the same time, overdiagnosis and overtreatment of prostatic tumors that will not progress to cause illness or death are frequent consequences of PSA-based screening. Although about 90% of men are currently treated for PSA-detected prostate cancer in the United States—usually with surgery or radiotherapy—the vast majority of men who are treated do not have prostate cancer death prevented or lives extended from that treatment, but are subjected to significant harms.
The USPSTF concludes that there is moderate certainty that the harms of PSA-based screening for prostate cancer outweigh the benefits.

Clinical Considerations

Patient Population Under Consideration

This recommendation applies to men in the general U.S. population. Older age is the strongest risk factor for development of prostate cancer. However, a more favorable balance of benefits and harms for PSA-based screening does not accompany this increase in risk. Across age ranges, African American men and men with a family history of prostate cancer have an increased risk for developing and dying from prostate cancer compared with other men. However, the observed risk differences for race/ethnicity or family history are each relatively small when compared with the risk differences seen with increasing age (1), and there are no data that suggest that the net benefit of PSA-based screening is altered by race or family history.
The USPSTF did not evaluate the use of the PSA test as part of a diagnostic strategy in men with symptoms that are highly suspicious for prostate cancer. This recommendation also does not include the use of the PSA test for surveillance after diagnosis and/or treatment of prostate cancer.

Screening Tests

PSA-based screening in men aged 50 to 74 years has been evaluated in five unique randomized, controlled trials of single or interval PSA testing with various PSA cut-off points and screening intervals, along with other screening modalities such as digital rectal examination or transrectal ultrasonography (411-14). None of these trials has shown a statistically significant prostate cancer mortality benefit in all enrolled men; most demonstrated a trend toward harm in the screened arm. Two meta-analyses also have not demonstrated a benefit of PSA screening on prostate cancer-specific or overall mortality (1015).
The U.S. Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) found a nonstatistically significant increase in prostate cancer mortality in the screened group after a median followup of 11.5 years, with results consistently favoring the nonscreened population, even after 11 years of followup (11).
Considering the findings of the two largest trials, the effect of PSA-based screening on death from prostate cancer after 10 years may range from a 0.03% absolute risk increase to a 0.06% absolute risk reduction (67). Screening tests or programs that do not incorporate PSA testing, including digital rectal examination alone, have not been evaluated adequately in controlled studies.

Treatment

Primary management strategies for PSA-detected prostate cancer include watchful waiting (observation and physical examination with palliative treatment of symptoms), active surveillance (periodic monitoring with PSA tests, physical examinations, and repeated prostate biopsy) with conversion to potentially curative treatment at the sign of disease progression or worsening prognosis, and surgery or radiation therapy (17). There is no consensus regarding the optimal treatment of localized disease. From 1986 through 2005, PSA-based screening likely resulted in approximately 1 million additional U.S. men being treated with surgery, radiation therapy, or both compared with before the test was introduced (18).
In the Scandinavian Prostate Cancer Group (SPCG)-4 trial, surgical management of localized, clinically-detected prostate cancer was associated with about a 6% absolute reduction in prostate cancer and all-cause mortality at 12–15 years’ followup; benefit appeared to be limited to men younger than age 65 years (9). Preliminary findings from the Prostate Cancer Intervention Versus Observation Trial (PIVOT) show that after 12 years, intention to treat with radical prostatectomy resulted in nonstatistically significant differences in disease-specific and all-cause mortality compared with observation that were less than 3% in absolute terms, in men with localized prostate cancer detected in the early PSA era (3).
Up to 0.5% of men will die within 30 days of undergoing radical prostatectomy, and 3%–7% will have serious surgical complications. Compared with men who choose watchful waiting, an additional 20% to 30% or more of men treated with radical prostatectomy will experience impotence, urinary incontinence, or both after 1 to 10 years. Radiation therapy is also associated with increases in erectile, bowel, and bladder dysfunction (68).

Other Considerations

Implementation

While the USPSTF discourages the use of screening tests for which the benefits do not outweigh the harms in the target population, it recognizes the common use of PSA screening in practice today and understands that some men will continue to request and some physicians will continue to offer screening. An individual man may choose to be screened because he places a higher value on the possibility of benefit, however small, than the known harms that accompany screening and treatment of screen-detected cancer, particularly the harms of overdiagnosis and overtreatment. This decision should be an informed decision, preferably made in consultation with a regular care provider. No man should be screened without his understanding and consent; community-based and employer-based screening that does not allow an informed choice should be discontinued.

Research Needs and Gaps

Because the balance of benefits and harms of prostate cancer screening is heavily influenced by overdiagnosis and overtreatment, research is necessary to identify ways to reduce the occurrence of these events, including evaluating the effect of altering PSA thresholds for an abnormal test or biopsy on false-positive rates and the detection of indolent disease. Similarly, new screening modalities must improve discriminatory accuracy between indolent disease and disease that is likely to clinically progress, thus reducing the number of men who require biopsy and subsequent treatment for disease that has a favorable prognosis without intervention. Research is also needed to compare the long-term benefits and harms of immediate treatment versus observation with delayed intervention in men with screen-detected prostate cancer. Two randomized, controlled trials—the PIVOT trial (19) and the U.K. Prostate Testing for Cancer and Treatment study (20)—are studying this issue. Preliminary results from the PIVOT trial potentially support raising the PSA threshold for recommending a biopsy and making treatment decisions in men subsequently diagnosed with prostate cancer.
Accurately ascertaining cause of death in older individuals can be problematic; as such, basing clinical recommendations on disease-specific mortality in the absence of an effect on all-cause mortality may not completely capture the health impact and goals of a screening and treatment program. Additional research is required to better assess and improve the reliability of prostate cancer mortality as a valid outcome measure in clinical trials, as well as the best application of the concomitant use of all-cause mortality.
Two large randomized, controlled trials of 5-alpha-reductase inhibitors (finasteride, dutasteride) have shown that these drugs reduce the risk of being diagnosed with prostate cancer in men receiving regular PSA tests. However, the observed reduction resulted from a decreased incidence of low-grade prostate cancer alone (Gleason score <6).The FDA has not approved finasteride and dutasteride for the prevention of prostate cancer, concluding that the drugs do not possess a favorable risk-benefit profile for this indication. The FDA cited associated adverse effects, including loss of libido and erectile dysfunction, but most importantly, it noted that in both trials there was an absolute increase in the incidence of high-grade prostate cancer in men randomized to finasteride or dutasteride compared with controls (21). Additional research would be useful to better understand the association of these drugs with the development of high-grade prostatic lesions, to determine the impact of 5-alpha-reductase inhibitors (or other potential preventive agents) on prostate cancer mortality and identify the population of men that might benefit most from prostate cancer prevention.

Discussion

Burden of Disease

An estimated 217,730 U.S. men received a prostate cancer diagnosis in 2010, and an estimated 32,050 men died from the disease (22). The average age of diagnosis was 67 years and the median age of death from prostate cancer from 2003 through 2007 was 80 years; 71% of deaths occurred in men older than age 75 years (1). African American men have a substantially higher prostate cancer incidence rate than white men (231.9 vs.146.3 cases per 100,000 men), and more than twice the prostate cancer mortality rate (56.3 vs. 23.6 deaths per 100,000 men, respectively) (22).
Prostate cancer is a clinically heterogeneous disease. Autopsy studies have shown that approximately one third of men aged 40–60 years have histologically evident prostate cancer (23); the proportion increases to as high as three fourths in men older than age 85 years (24). Most of these cases represent microscopic, well-differentiated lesions that are unlikely to be of clinical importance. The detection of lesions that are unlikely to be of clinical significance increases with frequency of PSA testing, lower thresholds to indicate an abnormal result, and the number of core biopsies obtained per diagnostic workup.

Scope of Review

The previous evidence update, performed for the USPSTF in 2008, found insufficient evidence that screening for prostate cancer improved health outcomes, including prostate cancer-specific and all-cause mortality, for men younger than age 75 years. In men aged 75 years or older, the USPSTF found adequate evidence that the incremental benefits of treatment for screen-detected prostate cancer are small to none, and that the harms of screening and treatment outweigh any potential benefits (25). After the publication of initial mortality results from two large randomized, controlled trials of prostate cancer screening, the USPSTF determined that a targeted update of the direct evidence on the benefits of PSA-based screening for prostate cancer should be performed (7). Additionally, the USPSTF requested a separate systematic review of the benefits and harms of treatment for localized prostate cancer (8).

Accuracy of Screening

The conventional PSA cut-off point of 4.0 ng/mL detects many cases of prostate cancer; however, some cases will be missed. Using a lower cut-off point detects more cases of cancer, but at the cost of labeling more men as potentially having cancer. For example, lowering the PSA cut-off point to 2.5 ng/mL would more than double the number of U.S. men aged 40 to 69 years with abnormal results (26), and the majority of these would be false-positive results. It also increases the likelihood of detection of indolent tumors with no clinical importance. Conversely, raising the PSA cut-off point to >10.0 ng/mL would reduce the number of men aged 50 to 69 years with abnormal results from approximately 1.2 million to around 352,000 individuals (26). There is no PSA cut-off point at which a man can be guaranteed to be free from prostate cancer (27).
There are inherent problems with the use of needle biopsy results as a reference standard to assess the accuracy of prostate cancer screening tests. Biopsy detection rates vary according to the number of biopsies performed during a single procedure; the more biopsies performed, the more cancer cases detected. More cancer cases detected with a “saturation” biopsy procedure (≥20 core biopsies) tend to increase the apparent specificity of an elevated PSA level; however, many of the additional cancer cases detected this way are unlikely to be clinically important. Thus, the accuracy of the PSA test for detecting clinically important prostate cancer cases cannot be determined with precision.
Variations of PSA screening, including the use of age-adjusted PSA cut-off points, free PSA, and PSA density, velocity, slope, and doubling time, have been proposed to improve detection of clinically important prostate cancer cases. However, no evidence has demonstrated that any of these testing strategies improve health outcomes, and some may even generate harms. One study found that utilizing PSA velocity in the absence of other indications could lead to 1 in 7 men undergoing a biopsy with no increase in predictive accuracy (28).

Effectiveness of Early Detection and Treatment

Two poor-quality randomized, controlled trials initiated in the 1980s in Sweden each demonstrated a nonstatistically significant trend toward increased prostate cancer mortality in groups invited to screening (1314). A third poor-quality trial from Canada showed similar results when an intention-to-screen analysis was used (12). The screening protocols for these trials varied; all included one or more PSA tests with cut-off points ranging from 3.0 to 10.0 ng/mL, in addition to digital rectal examination and/or transrectal ultrasonography.
The prostate component of the PLCO trial randomized 76,693 men aged 55 to 74 years to annual PSA screening for 6 years (and concomitant digital rectal examination for 4 years) or to usual care. It utilized a PSA cut-off point of 4.0 ng/mL. Diagnostic followup for positive screening tests and treatment choices were made by the participant and his personal physician; 90% of men with a prostate cancer diagnosis received active treatment (surgery, radiation, and/or hormonal therapy). After 7 years (complete followup), a nonstatistically significant trend toward increased prostate cancer mortality was seen in the screened arm (rate ratio [RR], 1.14 [95% CI, 0.75–1.70]) compared with men in the control arm. Similar findings were observed after 10 years. The primary criticism of this study relates to the high contamination rate; approximately 50% of men in the control arm received at least one PSA test during the study, although the investigators specifically increased both the number of screening intervals and the duration of followup to attempt to compensate for the contamination effects. About 40% of participants had received a PSA test in the 3 years prior to enrollment, though subgroup analyses stratified by history of PSA testing prior to study entry did not reveal differential effects on prostate cancer mortality rates (11).
The ERSPC trial randomized 182,000 men aged 50 to 74 years from seven European countries to PSA testing every 2 to 7 years or to usual care. PSA cut-off points ranged from 2.5 to 4.0 ng/mL, depending on study center (one center utilized a cut-off point of 10.0 ng/mL for several years). Sixty-six percent of men who received a prostate cancer diagnosis chose immediate treatment—surgery, radiation therapy, hormonal therapy, or some combination. After a median followup of 9 years, there was no statistically significant difference in prostate cancer mortality for all enrolled men (RR, 0.85 [95% CI, 0.73 to 1.00]). In a prespecified subgroup analysis limited to men aged 55 to 69 years, a statistically significant reduction in prostate cancer deaths was seen (RR, 0.80 [95% CI, 0.65–0.98]). Subgroup analyses demonstrated a nonsignificant trend toward increased prostate cancer mortality in screened men aged 50 to 54 and 70 to 74 years. The observed difference in prostate cancer mortality for the subgroup of men aged 55 to 69 years first emerged at approximately 9 years (the median length of followup for the trial); thus, the effect size may change (increase or disappear) with further followup. The authors estimated that 1,410 men would need to be screened and 48 additional men would need to be treated to prevent one prostate cancer death (4). Primary criticisms of this study relate to inconsistencies in age requirements, screening intervals, PSA thresholds, and enrollment procedures utilized among the study centers, as well as the exclusion of data from two study centers in the analysis. There is also concern that differential treatments between the study and control groups may have had an impact on outcomes. Of note, men in the screened group were more likely to have been treated in a university setting than men in the control group, and a control subject with high-risk prostate cancer was more likely than a screened subject to receive radiotherapy, expectant management, or hormonal therapy instead of radical prostatectomy (29).
After the publication of the ERSPC results, a single center from within that trial (Göteborg, Sweden) reported data separately. At this center, 20,000 men aged 50 to 64 years were randomized to an invitation to screening with PSA every 2 years or to usual care; median followup was 14 years. A PSA cut-off point of 3.0 ng/mL was initially used but was lowered to 2.5 ng/mL. Fifty-eight percent of participants diagnosed with prostate cancer in the screened arm chose immediate treatment. The rate ratio for prostate cancer mortality in the screened arm was 0.56 (95% CI, 0.39–0.82); the absolute risk reduction was 0.34% (16). Outcomes for 60% of this center’s participants had previously been reported as part of the full ERSPC publication, and comparative mortality rates are not available for any other individual study center, making it somewhat challenging to interpret these findings in context. An analysis in the overall ERSPC publication demonstrated that, of all participating countries, Sweden demonstrated the most favorable effect on the combined prostate cancer mortality reduction estimate, and that the overall study results for the “core” population were no longer statistically significant when findings from Sweden were excluded (4). None of the other centers published individual results.
Two meta-analyses found no statistically significant differences in prostate cancer mortality (RR, 0.88 [95% CI, 0.71–1.09] and 0.95 [95% CI, 0.85–1.07]) or overall mortality (RR, 0.99 [95% CI, 0.98–1.01] and 1.00 [95% CI, 0.98–1.02]) in men undergoing PSA-based screening compared with controls (1015).
There have been few randomized, controlled trials comparing prostate cancer treatments with watchful waiting. A randomized, controlled trial of 695 men with localized prostate cancer (SPCG-4) reported an 11.7% (95% CI, 4.8–18.6) absolute reduction in the risk of distant metastases in patients assigned to radical prostatectomy versus watchful waiting after 15 years’ followup. An absolute reduction in prostate cancer mortality (6.1% [95% CI, 0.2–12]) and a trend toward a reduction in all-cause mortality (6.6% [95% CI, −1.3 to 14.5]) were also observed over this time period. Subgroup analysis suggests that the benefits of prostatectomy may have been restricted to younger (<65 years) men, but were seen in men with PSA values less than 10 and Gleason histological scores of 6 or less. Additionally, radical prostatectomy reduced the use of hormonal therapy by 23.8%. The applicability of these findings to cancer detected via PSA-based screening is limited, as only 5% of participants were diagnosed with prostate cancer via some form of screening, 88% had palpable tumors, and more than 40% of participants presented with symptoms (930).
Preliminary results from the PIVOT trial have become available. The PIVOT trial was composed of men with prostate cancer detected after the initiation of widespread PSA testing and took place within the United States. The trial randomized 731 men aged 75 years or younger (mean age, 67 years) with a PSA value less than 50 ng/mL (mean PSA value, 10 ng/mL) and clinically localized prostate cancer to radical prostatectomy versus watchful waiting. One third of participants were African American. Based upon PSA value, Gleason score, and tumor stage, approximately 43% had low-risk tumors, 36% had intermediate-risk tumors, and 21% had high-risk tumors. After a median followup of 10 years, there were no statistically significant differences in prostate cancer-specific or all-cause mortality between men treated with surgery versus observation (absolute risk reduction, 2.7% [95% CI, −1.3 to 6.2] and 2.9% [95% CI, −4.1 to 10.3], respectively). Subgroup analysis found that the effect of radical prostatectomy compared with observation for both overall and prostate cancer mortality did not vary by patient characteristics (including age, race, health status and comorbidities, or Gleason histologic score), but there was variation by PSA level and possibly tumor risk category. In men in the radical prostatectomy group with a PSA value greater than 10 ng/mL at diagnosis, there was an absolute risk reduction of 7.2% (95% CI, 0.0–14.8) and 13.2% (95% CI, 0.9–24.9) for prostate cancer-specific and all-cause mortality, respectively, compared with men in the watchful waiting group. However, men in the radical prostatectomy group with PSA values of 10 ng/mL or less, or those with low-risk tumors, did not experience a reduction in prostate cancer-specific or all-cause mortality, and there was a potential suggestion (nonstatistically significant) of increased harm when compared with the watchful waiting arm (3).

Harms of Screening and Treatment

False-positive PSA test results are common and vary depending on the PSA cut-off point and frequency of screening. After four PSA tests, men in the screening arm of PLCO had a 12.9% cumulative risk of receiving at least one false-positive result (defined as PSA >4.0 ng/mL and no prostate cancer diagnosis after 3 years) and a 5.5% risk of having at least one biopsy due to a false-positive result (31). Men with false-positive PSA test results are more likely to worry specifically about prostate cancer, have a higher perceived risk for prostate cancer, and report problems with sexual function compared with control participants for up to 1 year after testing (32). In one study of men with false-positive PSA test results, 26% reported that they had experienced moderate to severe pain during the biopsy; men with false-positive results were also more likely to undergo repeated PSA testing and additional biopsies during the 12 months following the initial negative biopsy (33).
Harms of prostate biopsy reported by the Rotterdam center of the ERSPC trial include persistent hematospermia (50.4%), hematuria (22.6%), fever (3.5%), urinary retention (0.4%), and hospitalization for signs of prostatitis or urosepsis (0.5%) (34). Pain and discomfort are also associated with prostate biopsy. The documented range varies widely, from around one quarter to more than 90% of men, depending on the definition of “pain/discomfort” utilized, use of analgesia, number of core biopsies taken (as taking more samples appears to be associated with greater pain), and age of the patient (as younger men have reported higher levels and frequencies of pain than older individuals) (35).
The low specificity of the PSA test coupled with its inability to distinguish indolent from aggressive tumors means that a substantial number of men are being overdiagnosed with prostate cancer. Estimates derived from the ERSPC trial suggest overdiagnosis rates of 48% to 67% of prostate cancer cases detected by the PSA test (3637). Overdiagnosis is of particular concern because although these men cannot benefit from any associated treatment, they are still subject to the harms of a given therapy. Evidence indicates that nearly 90% of men diagnosed with clinically localized prostate cancer through PSA testing undergo early treatment—primarily radical prostatectomy and radiation therapy.
Radical prostatectomy is associated with a 20% increased absolute risk of urinary incontinence and a 30% increased absolute risk of impotence compared with watchful waiting (i.e., increased 20% over a median rate of 6% and 30% over a median rate of 45%, respectively) after 1 to 10 years. Perioperative deaths or cardiovascular events occur in about 0.5% and 0.6%–3% of patients (68). Comparative data on outcomes using different surgical techniques are limited; one population-based observational cohort study using U.S. Surveillance, Epidemiology, and End Results (SEER) and Medicare linked data found that minimally invasive/robotic radical prostatectomy for prostate cancer was associated with higher risks for genitourinary complications, incontinence, and erectile dysfunction than open radical prostatectomy (38).
Radiation therapy is associated with a 17% absolute increase in risk of impotence (i.e., increased 17% over a median rate of 50%) and an increased risk of bowel dysfunction compared with watchful waiting after 1 to 10 years; the effect is most pronounced in the first few months after treatment (68).
Localized prostate cancer is not an FDA-approved indication for androgen deprivation therapy, and clinical outcomes for older men receiving this treatment for localized disease are worse than for those who are conservatively managed (39). Androgen deprivation therapy is associated with an increased risk of impotence compared with watchful waiting (absolute risk difference, 43%), as well as systemic effects such as hot flashes and gynecomastia (68). In advanced prostate cancer, androgen deprivation therapy may generate other serious harms, including diabetes, myocardial infarction, or coronary heart disease; however, these effects have not been well studied in men treated for localized prostate cancer.

Estimate of Magnitude of Net Benefit

No trial has shown a decrease in overall mortality with the use of PSA-based screening through 11 years of followup. Most randomized trials have failed to demonstrate a reduction in prostate cancer deaths with the use of the PSA test, and several—including the PLCO trial—have suggested an increased risk in screened men, potentially due to morbidities associated with overdiagnosis and overtreatment. In a prespecified subgroup of men aged 55 to 69 years in the ERSPC trial, a small (0.07%) absolute reduction in prostate cancer deaths was observed after a median followup of 9 years. No statistically significant effect was seen when all enrolled men (ages 50 to 74 years) were included in the analysis. The time until any potential cancer-specific mortality benefit for PSA-based screening emerges is long (at least 9 to 10 years), and most men with prostate cancer die of causes other than prostate cancer (40); as such, even among men diagnosed with prostate cancer via PSA screening, very few will have prostate cancer death prevented or their lives extended as a result of screening.
The harms of PSA-based screening for prostate cancer include a high rate of false-positive results and accompanying negative psychological effects, complications associated with diagnostic biopsy, and, most importantly, a risk for overdiagnosis coupled with overtreatment. Depending on the modality employed, treatments for prostate cancer carry the risk of death, cardiovascular events, urinary incontinence, impotence, and bowel dysfunction.
The mortality benefits of PSA-based prostate cancer screening through 10 years are small to none, while the harms are moderate to substantial. Therefore, the USPSTF concludes with moderate certainty that PSA-based screening for prostate cancer, as currently utilized and studied in randomized, controlled trials, has no net benefit.

How Does Evidence Fit With Biological Understanding?

PSA-based screening and subsequent treatment, as currently practiced in the United States, presupposes that the majority of asymptomatic prostate cancer cases will ultimately become clinically important and lead to poor health outcomes. However, long-term, population-based cohort studies of conservatively managed men with localized prostate cancer do not support this hypothesis. A review of the Connecticut Tumor Registry—initiated before the PSA era—examined the long-term probability of prostate cancer death among men (median age at diagnosis, 69 years) whose tumors were mostly incidentally identified at the time of transurethral resection or open surgery for benign prostatic hyperplasia. Men received observation alone or early or delayed androgen withdrawal therapy. After 15 years of followup, the overall risk of dying from prostate cancer was 18 deaths per 1,000 person-years. For men with well-differentiated prostate cancer, it was 6 deaths per 1,000 person-years; far more of these men had died from causes other than prostate cancer (75% vs. 7%) (41). An analysis of the SEER database after the widespread introduction of PSA-based screening examined the risk of death in men with localized prostate cancer who did not undergo initial attempted curative therapy. The 10-year prostate cancer mortality rate for well- or moderately-differentiated tumors among men aged 66–69 years at diagnosis was 0%–7%, depending on tumor stage, versus 0%–22% for other causes. The relative proportion of deaths attributable to other causes compared with prostate cancer increased substantially with age at prostate cancer diagnosis (42).

Update of Previous USPSTF Recommendation

This recommendation replaces the 2008 recommendation (25). Whereas the USPSTF previously recommended against PSA-based screening for prostate cancer in men aged 75 years and older and concluded that the evidence was insufficient to make a recommendation in younger men, the USPSTF now recommends against PSA-based screening for prostate cancer in all age groups.

Recommendations of Others

The American Urological Association recommends that PSA screening should be offered to men aged 40 years or older (43). The American Cancer Society emphasizes informed decisionmaking for prostate cancer: men at average risk should receive information beginning at age 50 years, while African American men or men with a family history of prostate cancer should receive information at age 45 years (44). The American College of Physicians (45) and the American College of Preventive Medicine (46) recommend that clinicians discuss the potential benefits and harms of PSA screening with men aged 50 years and older, consider their patients’ preferences, and individualize screening decisions.

Appendix: U.S. Preventive Services Task Force

Members of the U.S. Preventive Services Task Force* at the time this recommendation was drafted are Virginia A. Moyer, MD, MPH, Chair (Baylor College of Medicine, Houston, Texas); Michael L. LeFevre, MD, MSPH, Co-Vice Chair (University of Missouri School of Medicine, Columbia, Missouri); Albert L. Siu, MD, MSPH, Co-Vice Chair (Mount Sinai School of Medicine, New York, New York); Kirsten Bibbins-Domingo, PhD, MD (University of California, San Francisco, California); Susan J. Curry, PhD (University of Iowa College of Public Health, Iowa City, Iowa); Glenn Flores, MD (University of Texas Southwestern, Dallas, Texas); Adelita Gonzales Cantu, RN, PhD (University of Texas Health Science Center, San Antonio, Texas); David C. Grossman, MD, MPH (Group Health Cooperative, Seattle, Washington); George J. Isham, MD, MS (HealthPartners, Minneapolis, Minnesota); Rosanne M. Leipzig, MD, PhD (Mount Sinai School of Medicine, New York, New York); Joy Melnikow, MD, MPH (University of California Davis, Sacramento, California); Bernadette Melnyk, PhD, RN (Ohio State University College of Nursing, Columbus, Ohio); Wanda K. Nicholson, MD, MPH, MBA (University of North Carolina School of Medicine, Chapel Hill, North Carolina); Carolina Reyes, MD, MPH (Virginia Hospital Center, Arlington, Virginia); J. Sanford Schwartz, MD, MBA (University of Pennsylvania Medical School and the Wharton School, Philadelphia, Pennsylvania); and Timothy J. Wilt, MD, MPH (University of Minnesota Department of Medicine and Minneapolis Veteran Affairs Medical Center, Minneapolis, Minnesota). Ned Calonge, MD, MPH, a previous Task Force member, also made significant contributions to this recommendation.
* For a list of current Task Force members, go to http://www.uspreventiveservicestaskforce.org/about.htm.

Table 1: What the Grades Mean and Suggestions for Practice

Grade Definition Suggestions for Practice
A The USPSTF recommends the service. There is high certainty that the net benefit is substantial. Offer/provide this service.
B The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. Offer/provide this service.
C The USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is at least moderate certainty that the net benefit is small. Offer/provide this service only if other considerations support offering or providing the service in an individual patient.
D The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. Discourage the use of this service.
I Statement The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. Read “Clinical Considerations” section of USPSTF Recommendation Statement. If the service is offered, patients should understand the uncertainty about the balance of benefits and harms.



Table 2: Levels of Certainty Regarding Net Benefit

Level of Certainty Description
High The available evidence usually includes consistent results from well-designed, well-conducted studies in representative primary care populations. These studies assess the effects of the preventive service on health outcomes. This conclusion is therefore unlikely to be strongly affected by the results of future studies.
Moderate The available evidence is sufficient to determine the effects of the preventive service on health outcomes, but confidence in the estimate is constrained by factors such as:

  • the number, size, or quality of individual studies;
  • inconsistency of findings across individual studies;
  • limited generalizability of findings to routine primary care practice;
  • or lack of coherence in the chain of evidence.
As more information becomes available, the magnitude or direction of the observed effect could change, and this change may be large enough to alter the conclusion.
Low The available evidence is insufficient to assess effects on health outcomes. Evidence is insufficient because of:

  • the limited number or size of studies;
  • important flaws in study design or methods;
  • inconsistency of findings across individual studies;
  • gaps in the chain of evidence;
  • findings not generalizable to routine primary care practice; or
  • a lack of information on important health outcomes.
More information may allow an estimation of effects on health outcomes.
The U.S. Preventive Services Task Force defines certainty as “likelihood that the USPSTF assessment of the net benefit of a preventive service is correct”. The net benefit is defined as benefit minus harm of the preventive service as implemented in a general, primary care population. The USPSTF assigns a certainty level based on the nature of the overall evidence available to assess the net benefit of a preventive service.

References

1. Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, et al. SEER Cancer Statistics Review, 1975–2008. Bethesda, MD: National Cancer Institute; 2011. Accessed athttp://seer.cancer.gov/csr/1975_2008/index.html on 6 October 2011.
2. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349:215-24.
3. Wilt TJ. The VA/NCI/AHRQ Cooperative Studies Program #407: Prostate cancer Intervention Versus Observation Trial (PIVOT): main results from a randomized trial comparing radical prostatectomy to watchful waiting in men with clinically localized prostate cancer. Paper presented at: 107th Annual Meeting of the American Urological Association; May 2011; Washington, DC. 
4. Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320-8.
5. Lin K, Lipsitz R, Miller T, Janakiraman S; U.S. Preventive Services Task Force. Benefits and harms of prostate-specific antigen screening for prostate cancer: an evidence update for the U.S. Preventive Services Task Force. Ann Intern Med. 2008;149:192-9.
6. Chou R, Croswell JM, Dana T, Bougatsos C, Blazina I, et al. Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2011 Oct 7. [Epub ahead of print]
7. Lin K, Croswell JM, Koenig H, Lam C, Maltz A. Prostate-Specific Antigen-Based Screening for Prostate Cancer: An Evidence Update for the U.S. Preventive Services Task Force. Evidence Synthesis No. 90. AHRQ Publication No. 12-05160-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2011.
8. Chou R, Dana T, Bougatsos C, Fu R, Blazina I, et al. Treatments for Localized Prostate Cancer: Systematic Review to Update the 2002 U.S. Preventive Services Task Force Recommendation. Evidence Synthesis No. 91. AHRQ Publication No. 12-05161-EF-2. Rockville, MD: Agency for Healthcare Research and Quality; 2011.
9. Bill-Axelson A, Holmberg L, Ruutu M, Garmo H, Stark JR, et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2011;364:1708-17.
10. Ilic D, O’Connor D, Green S, Wilt TJ. Screening for prostate cancer: an updated Cochrane systematic review. BJU Int. 2011;107:882-91.
11. Andriole GL, Crawford ED, Grubb RL 3rd, Buys SS, Chia D, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310-9.
12. Labrie F, Candas B, Cusan L, Gomez JL, Bélanger A, et al. Screening decreases prostate cancer mortality: 11-year follow-up of the 1988 Quebec prospective randomized controlled trial. Prostate. 2004;59:311-8.
13. Sandblom G, Varenhorst E, Rosell J, Löfman O, Carlsson P. Randomised prostate cancer screening trial: 20 year follow-up. BMJ. 2011;342:d1539.
14. Kjellman A, Akre O, Norming U, Törnblom M, Gustafsson O. 15-year followup of a population based prostate cancer screening study. J Urol. 2009;181:1615-21.
15. Djulbegovic M, Beyth RJ, Neuberger MM, Stoffs TL, Vieweg J, et al. Screening for prostate cancer: systematic review and meta-analysis of randomised controlled trials. BMJ. 2010;341:c4543.
16. Hugosson J, Carlsson S, Aus G, Bergdahl S, Khatami A, et al. Mortality results from the Göteborg randomised population-based prostate-cancer screening trial. Lancet Oncol. 2010;11:725-32.
17. Wilt TJ, MacDonald R, Rutks I, Shamliyan TA, Taylor BC, Kane RL. Systematic review: comparative effectiveness and harms of treatments for clinically localized prostate cancer.Ann Intern Med. 2008;148:435-48.
18. Welch HG, Albertsen PC. Prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening: 1986–2005. J Natl Cancer Inst. 2009;101:1325-9.
19. Wilt TJ, Brawer MK, Barry MJ, Jones KM, Kwon Y, et al. The Prostate cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy to watchful waiting for men with clinically localized prostate cancer. Contemp Clin Trials. 2009;30:81-7.
20. Moore AL, Dimitropoulou P, Lane A, Powell PH, Greenberg DC, et al. Population-based prostate-specific antigen testing in the UK leads to a stage migration of prostate cancer.BJU Int. 2009;104:1592-8.
21. Theoret MR, Ning YM, Zhang JJ, Justice R, Keegan P, Pazdur R. The risks and benefits of 5a-reductase inhibitors for prostate-cancer prevention. N Engl J Med. 2011;365:97-9.
22. American Cancer Society. Cancer Facts & Figures 2010. Atlanta: American Cancer Society; 2010. Accessed athttp://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/cancer-facts-and-figures-2010 on 6 October 2011.
23. Sakr WA, Haas GP, Cassin BF, Pontes JE, Crissman JD. The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients. J Urol. 1993;150:379-85.
24. Grönberg H. Prostate cancer epidemiology. Lancet. 2003;361:859-64.
25. U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149:185-91.
26. Welch HG, Schwartz LM, Woloshin S. Prostate-specific antigen levels in the United States: implications of various definitions for abnormal. J Natl Cancer Inst. 2005;97:1132-7.
27. Thompson IM, Ankerst DP, Chi C, Lucia MS, Goodman PJ, et al. Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower. JAMA. 2005;294:66-70.
28. Vickers AJ, Till C, Tangen CM, Lilja H, Thompson IM. An empirical evaluation of guidelines on prostate-specific antigen velocity in prostate cancer detection. J Natl Cancer Inst. 2011;103:462-9.
29. Wolters T, Roobol MJ, Steyerberg EW, van den Bergh RC, Bangma CH, et al. The effect of study arm on prostate cancer treatment in the large screening trial ERSPC. Int J Cancer. 2010;126:2387-93.
30. Bill-Axelson A, Holmberg L, Filén F, Ruutu M, Garmo H, et al. Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian Prostate Cancer Group-4 randomized trial. J Natl Cancer Inst. 2008;100:1144-54.
31. Croswell JM, Kramer BS, Kreimer AR, Prorok PC, Xu JL, et al. Cumulative incidence of false-positive results in repeated, multimodal cancer screening. Ann Fam Med. 2009;7:212-22.
32. McNaughton-Collins M, Fowler FJ Jr, Caubet JF, Bates DW, Lee JM, et al. Psychological effects of a suspicious prostate cancer screening test followed by a benign biopsy result. Am J Med. 2004;117:719-25.
33. Fowler FJ Jr, Barry MJ, Walker-Corkery B, Caubet JF, Bates DW, et al. The impact of a suspicious prostate biopsy on patients’ psychological, socio-behavioral, and medical care outcomes. J Gen Intern Med. 2006;21:715-21.
34. Raaijmakers R, Kirkels WJ, Roobol MJ, Wildhagen MF, Schröder FH. Complication rates and risk factors of 5802 transrectal ultrasound-guided sextant biopsies of the prostate within a population-based screening program. Urology. 2002;60:826-30.
35. De Sio M, D’Armiento M, Di Lorenzo G, Damiano R, Perdonà S, et al. The need to reduce patient discomfort during transrectal ultrasonography-guided prostate biopsy: what do we know? BJU Int. 2005;96:977-83.
36. Welch HG, Black WC. Overdiagnosis in cancer. J Natl Cancer Inst. 2010;102:605-13.
37. Draisma G, Boer R, Otto SJ, van der Cruijsen IW, Damhuis RA, et al. Lead times and overdetection due to prostate-specific antigen screening: estimates from the European Randomized Study of Screening for Prostate Cancer. J Natl Cancer Inst. 2003;95:868-78.
38. Hu JC, Gu X, Lipsitz SR, Barry MJ, D’Amico AV, et al. Comparative effectiveness of minimally invasive vs open radical prostatectomy. JAMA. 2009;302:1557-64.
39. Lu-Yao GL, Albertsen PC, Moore DF, Shih W, Lin Y, et al. Survival following primary androgen deprivation therapy among men with localized prostate cancer. JAMA. 2008;300:173-81.
40. Lu-Yao G, Stukel TA, Yao SL. Changing patterns in competing causes of death in men with prostate cancer: a population based study. J Urol. 2004;171:2285-90.
41. Albertsen PC, Hanley JA, Fine J. 20-year outcomes following conservative management of clinically localized prostate cancer. JAMA. 2005;293:            2095-101      .
42. Lu-Yao GL, Albertsen PC, Moore DF, Shih W, Lin Y, et al. Outcomes of localized prostate cancer following conservative management. JAMA. 2009;302:1202-9.
43. Carroll P, Albertsen PC, Greene K, Babaian RJ, Carter HB, et al. Prostate-Specific Antigen Best Practice Statement: 2009 Update. Linthicum, MD: American Urological Assocation; 2009. Accessed at http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines/main-reports/psa09.pdf on 6 October 2011.
44. Wolf AM, Wender RC, Etzioni RB, Thompson IM, D’Amico AV, et al. American Cancer Society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin. 2010;60:70-98.
45. American College of Physicians. Screening for prostate cancer. Ann Intern Med. 1997;126:480-4.
46. Lim LS, Sherin K; ACPM Prevention Practice Committee. Screening for prostate cancer in U.S. men: ACPM Position Statement on Preventive Practice. Am J Prev Med. 2008;34:164-70.
Current as of October 2011

Internet Citation:
U.S. Preventive Services Task Force. Screening for Prostate Cancer: Draft Recommendation Statement. http://www.uspreventiveservicestaskforce.org/uspstf12/prostate/draftrecprostate.htm

PSA & New York Times


Healthy men should no longer receive a P.S.A. blood test to screen forprostate cancer because the test does not save lives over all and often leads to more tests and treatments that needlessly cause pain,impotence and incontinence in many, a key government health panel has decided.

Well

Tara Parker-Pope answers some of the most common questions about P.S.A. testing and what the task force recommendations mean for men.

Table 1. Side-effects and effects on recovery ...Image via Wikipedia

The draft recommendation, by the United States Preventive Services Task Force and due for official release next week, is based on the results of five well-controlled clinical trials and could substantially change the care given to men 50 and older. There are 44 million such men in the United States, and 33 million of them have already had a P.S.A. test — sometimes without their knowledge — during routine physicals.

The task force’s recommendations are followed by most medical groups. Two years ago the task force recommended that women in their 40s should no longer get routine mammogramssetting off a firestorm of controversy. The recommendation to avoid the P.S.A. test is even more forceful and applies to healthy men of all ages.
“Unfortunately, the evidence now shows that this test does not save men’s lives,” said Dr. Virginia Moyer, a professor of pediatrics at Baylor College of Medicine and chairwoman of the task force. “This test cannot tell the difference between cancers that will and will not affect a man during his natural lifetime. We need to find one that does.”
But advocates for those with prostate cancer promised to fight the recommendation. Baseball’s Joe Torre, the financier Michael Milken and Rudolph W. Giuliani, the former New York City mayor, are among tens of thousands of men who believe a P.S.A. test saved their lives.
The task force can also expect resistance from some drug makers and doctors. Treating men with high P.S.A. levels has become a lucrative business. Some in Congress have criticized previous decisions by the task force as akin to rationing, although the task force does not consider cost in its recommendations.
“We’re disappointed,” said Thomas Kirk, of Us TOO, the nation’s largest advocacy group for prostate cancer survivors. “The bottom line is that this is the best test we have, and the answer can’t be, ‘Don’t get tested.’ ”
But that is exactly what the task force is recommending. There is no evidence that a digital rectal exam or ultrasound are effective, either. “There are no reliable signs or symptoms of prostate cancer,” said Dr. Timothy J. Wilt, a member of the task force and a professor of medicine at the University of Minnesota. Frequency and urgency of urinating are poor indicators of disease, since the cause is often benign.
The P.S.A. test, routinely given to men 50 and older, measures a protein — prostate-specific antigen — that is released by prostate cells, and there is little doubt that it helps identify the presence of cancerous cells in the prostate. But a vast majority of men with such cells never suffer ill effects because their cancer is usually slow-growing. Even for men who do have fast-growing cancer, the P.S.A. test may not save them since there is no proven benefit to earlier treatment of such invasive disease.
As the P.S.A. test has grown in popularity, the devastating consequences of the biopsies and treatments that often flow from the test have become increasingly apparent. From 1986 through 2005, one million men received surgery, radiation therapy or both who would not have been treated without a P.S.A. test, according to the task force. Among them, at least 5,000 died soon after surgery and 10,000 to 70,000 suffered serious complications. Half had persistent blood in their semen, and 200,000 to 300,000 suffered impotence, incontinence or both. As a result of these complications, the man who developed the test, Dr. Richard J. Ablin, has called its widespread use a “public health disaster.”
One in six men in the United States will eventually be found to have prostate cancer, making it the second most common form of cancer in men after skin cancer. An estimated 32,050 men died of prostate cancer last year and 217,730 men received the diagnosis. The disease is rare before age 50, and most deaths occur after age 75.
Not knowing what is going on with one’s prostate may be the best course, since few men live happily with the knowledge that one of their organs is cancerous. Autopsy studies show that a third of men ages 40 to 60 have prostate cancer, a share that grows to three-fourths after age 85.
P.S.A. testing is most common in men over 70, and it is in that group that it is the most dangerous since such men usually have cancerous prostate cells but benefit the least from surgery and radiation. Some doctors treat patients who have high P.S.A. levels with drugs that block male hormones, although there is no convincing evidence that these drugs are helpful in localized prostate cancer and they often result in impotence, breast enlargement and hot flashes.
Of the trials conducted to assess the value of P.S.A. testing, the two largest were conducted in Europe and the United States. Both “demonstrate that if any benefit does exist, it is very small after 10 years,” according to the task force’s draft recommendation statement.
The European trial had 182,000 men from seven countries who either got P.S.A. testing or did not. When measured across all of the men in the study, P.S.A. testing did not cut death rates in nine years of follow-up. But in men ages 55 to 69, there was a very slight improvement in mortality. The American trial, with 76,693 men, found that P.S.A. testing did not cut death rates after 10 years.
Dr. Eric Klein of the Cleveland Clinic, an expert in prostate cancer, said he disagreed with the task force’s recommendations. Citing the European trial, he said “I think there’s a substantial amount of evidence from randomized clinical trials that show that among younger men, under 65, screening saves lives.”
The task force’s recommendations apply only to healthy men without symptoms. The group did not consider whether the test is appropriate in men who already have suspicious symptoms or those who have already been treated for the disease. The recommendations will be open to public comment next week before they are finalized.
Recommendations of the task force often determine whether federal health programs likeMedicare and private health plans envisioned under the health reform law pay fully for a test. But legislation already requires Medicare to pay for P.S.A. testing no matter what the task force recommends.
Still, the recommendations will most likely be greeted with trepidation by the Obama administration, which has faced charges from Republicans that it supports rationing of health care services, which have been politically effective, regardless of the facts.
After the task force’s recommendation against routine mammograms for women under 50, Health and Human Services Secretary Kathleen Sibelius announced that the government would continue to pay for the test for women in their 40s. On Thursday, the administration announced with great fanfare that as a result of the health reform law, more people with Medicare were getting free preventive services like mammograms.
Dr. Michael Rawlins, chairman of the National Institute for Health and Clinical Excellence in Britain, said he was given a P.S.A. test several years ago without his knowledge. He then had a biopsy, which turned out to be negative. But if cancer had been detected, he would have faced an awful choice, he said: “Would I want to have it removed, or would I have gone for watchful waiting with all the anxieties of that?” He said he no longer gets the test.
But Dan Zenka, a spokesman for the Prostate Cancer Foundation, said a high P.S.A. test result eventually led him to have his prostate removed, a procedure that led to the discovery that cancer had spread to his lymph nodes. His organization supports widespread P.S.A. testing. “I can tell you it saved my life,” he said.

Cribado de cancer de prostata – Screening of prostaste cancer


Prostate and bladder, sagittal section.Image via Wikipedia

Editorial del NEJM 26 de Marzo 2009


In the United States, most men over the age of 50 years have had a prostate-specific–antigen (PSA) test,1 despite the absence of evidence from large, randomized trials of a net benefit. Moreover, about 95% of male urologists and 78% of primary care physicians who are 50 years of age or older report that they have had a PSA test themselves,2 a finding that suggests they are practicing what they preach. And indeed, U.S. death rates from prostate cancer have fallen about 4% per year since 1992, five years after the introduction of PSA testing.3 Perhaps the answer to the PSA controversy is already staring us in the face. At the same time, practice guidelines cite the unproven benefit of PSA screening, as well as the known side effects,4,5 which largely reflect the high risks of overdiagnosis and overtreatment that PSA-based screening engenders.6
The first reports from two large, randomized trials that many observers hoped would settle the controversy appear in this issue of the Journal. In the U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, Andriole et al.7 report no mortality benefit from combined screening with PSA testing and digital rectal examination during a median follow-up of 11 years.8 In the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial, Schröder et al.8 report that PSA screening without digital rectal examination was associated with a 20% relative reduction in the death rate from prostate cancer at a median follow-up of 9 years, with an absolute reduction of about 7 prostate cancer deaths per 10,000 men screened.8 The designs of the two trials are different and provide complementary insights.
First, one must ask, “Why were these results published now?” Neither set of findings seems definitive; that is, there was neither a clear declaration of futility in the PLCO trial nor an unambiguous net benefit in the ERSPC trial. Both studies are ongoing, with future updates promised. The report on the ERSPC trial follows a third planned interim analysis, which found a marginally significant decrease in prostate-cancer mortality after adjustment of the P value for the two previous looks in an attempt to avoid a false positive conclusion (yet apparently preserving no alpha for the planned final analysis). On the other hand, the investigators in the PLCO trial made the decision to publish their results now because of concern about the emerging evidence of net harm compared with potential benefits associated with PSA screening. Both decisions to publish now can be criticized as premature, leaving clinicians and patients to deal with the ambiguity.
The ERSPC trial is actually a collection of trials in different countries with different eligibility criteria, randomization schemes, and strategies for screening and follow-up. The report by Schröder et al. is based on a predefined core group of men between 55 and 69 years of age at study entry. Subjects were generally screened every 4 years, and 82% were screened at least once. Contamination of the control group with screening as part of usual care is not described. Biopsies were generally recommended for subjects with PSA levels of more than 3.0 ng per milliliter. It is unclear whether the clinicians and hospitals treating patients with prostate cancer differed between the two study groups.
Adjudications of causes of death were made by committees whose members were unaware of study-group assignments, though not of treatments. This point is important, since previous research has suggested that the cause of death is less likely to be attributed to prostate cancer among men receiving attempted curative treatment.9 Misattribution might then create a bias toward screening, since the diagnosis of more early-stage cancers in the ERSPC trial led to substantially more attempted curative treatments.
The ERSPC interim analysis revealed a 20% reduction in prostate-cancer mortality; the adjusted P value was 0.04. The estimated absolute reduction in prostate-cancer mortality of about 7 deaths per 10,000 men after 9 years of follow-up, if real and not the result of chance or bias, must be weighed against the additional interventions and burdens. The 73,000 men in the screening group underwent more than 17,000 biopsies, undoubtedly many more than did men in the control group, though the latter is not reported. Men had a substantially higher cumulative risk of receiving the diagnosis of prostate cancer in the screening group than in the control group (820 vs. 480 per 10,000 men). Diagnosis led to more treatment, with 277 versus 100 per 10,000 men undergoing radical prostatectomy and 220 versus 123 per 10,000 undergoing radiation therapy with or without hormones, respectively (tentative estimates given the unknown treatments in both groups).
Although estimates of the benefit of screening were somewhat greater for men who actually underwent testing (taking into account noncompliance) than for those who were not tested, the side effects would be proportionately higher as well. Given these trade-offs, the promise of future ERSPC analyses addressing quality of life and cost-effectiveness is welcome indeed. The ERSPC results also reemphasize the need for caution in screening men over the age of 69 years, given an early trend toward higher prostate-cancer mortality with screening in this age subgroup, although this finding may well be due to chance alone.
A final point to make about the ERSPC trial is that to the extent that the diagnosis and treatment of prostate cancer in the screening group differed from those in the control group, it becomes difficult to dissect out the benefit attributable to screening versus improved treatment once prostate cancer was suspected or diagnosed. A similar distribution of treatments among seemingly similar patients with cancer is only partially reassuring in this regard.
Despite a longer median follow-up, the PLCO trial was smaller and therefore less mature than the ERSPC trial, with 174 prostate-cancer deaths driving the power of the study, as compared with 540 such deaths in the ERSPC trial. The screening protocol was homogeneous across sites with an enrollment age of 55 to 74 years and annual PSA tests for 6 years and digital rectal examinations for 4 years, with about 85% compliance. Subjects in the screening group who had a suspicious digital rectal examination or a PSA level of more than 4.0 ng per milliliter received a recommendation for further evaluation. This strategy helped to ensure that any difference in outcome was attributable to screening, rather than downstream management. The effectiveness of screening, of course, will be determined by the effectiveness of subsequent “usual care,” but this is the same usual care that many practitioners assume has been responsible for the falling U.S. death rate from prostate cancer. Adjudication of causes of death was similar to that in the ERSPC trial.
Though the PLCO trial has shown no significant effect on prostate-cancer mortality to date, the relatively low number of end points begets a wide confidence interval, which includes at its lower margin the point estimate of effect from the ERSPC trial. Other likely explanations for the negative findings are high levels of prescreening in the PLCO population and contamination of the control group. Contamination was assessed by periodic cross-sectional surveys, with about half the subjects in the control group undergoing PSA testing by year 5. It is unclear whether these estimates reflect testing that year or since trial inception; if the former, the cumulative incidence may be even higher. The smaller difference in screening intensity between the two study groups in the PLCO trial, as compared with the ERSPC trial, is reflected in a smaller risk of overdiagnosis (23% vs. more than 70%) and a less impressive shift in cancer stage and grade distributions. Given that study-group contamination from the use of digital rectal examination was less problematic (only about 25%), ongoing results from both of these trials may necessitate rethinking the role of digital rectal examination in cancer screening.
After digesting these reports, where do we stand regarding the PSA controversy? Serial PSA screening has at best a modest effect on prostate-cancer mortality during the first decade of follow-up. This benefit comes at the cost of substantial overdiagnosis and overtreatment. It is important to remember that the key question is not whether PSA screening is effective but whether it does more good than harm. For this reason, comparisons of the ERSPC estimates of the effectiveness of PSA screening with, for example, the similarly modest effectiveness of breast-cancer screening cannot be made without simultaneously appreciating the much higher risks of overdiagnosis and overtreatment associated with PSA screening.
The report on the ERSPC trial appropriately notes that 1410 men would need to be offered screening and an additional 48 would need to be treated to prevent one prostate-cancer death during a 10-year period, assuming the point estimate is correct. And although the PLCO trial may not have the power as yet to detect a similarly modest benefit of screening, its power is already more than adequate to detect important harm through overdiagnosis. However, the implications of the trade-offs reflected in these data, like beauty, will be in the eye of the beholder. Some well-informed clinicians and patients will still see these trade-offs as favorable; others will see them as unfavorable. As a result, a shared decision-making approach to PSA screening, as recommended by most guidelines, seems more appropriate than ever.
Finally, despite these critiques, both groups of investigators deserve high praise for their persistence and perseverance: to manage such monstrous trials is a herculean task, made no easier when so many observers think the results are self-evident. Further analyses will be needed from these trials, as well as from others — such as the Prostate Cancer Intervention Versus Observation Trial (PIVOT) in the United States (ClinicalTrials.gov number, NCT00007644 [ClinicalTrials.gov] )10 and the Prostate Testing for Cancer and Treatment (PROTECT) trial in the United Kingdom (Current Controlled Trials number, ISRCTN20141297 [controlled-trials.com] )11 — if the PSA controversy is finally to sleep the big sleep.
No potential conflict of interest relevant to this article was reported.

Source Information

From Massachusetts General Hospital and Harvard Medical School, Boston.

This article (10.1056/NEJMe0901166) was published at NEJM.org on March 18, 2009.
References

  1. Ross LE, Berkowitz Z, Ekwueme DU. Use of the prostate-specific antigen test among U.S. men: findings from the 2005 National Health Interview Survey. Cancer Epidemiol Biomarkers Prev 2008;17:636-644. [Free Full Text]
  2. Chan EC, Barry MJ, Vernon SW, Ahn C. Brief report: physicians and their personal prostate cancer-screening practices with prostate-specific antigen: a national survey. J Gen Intern Med 2006;21:257-259. [CrossRef][ISI][Medline]
  3. Ries LAG, Melbert D, Krapcho M, et al. SEER cancer statistics review, 1975–2005. Bethesda, MD: National Cancer Institute, 2008. (Accessed March 6, 2009 at http://seer.cancer.gov/csr/1975_2005/.)
  4. Smith RA, Cokkinides V, Brawley OW. Cancer screening in the United States, 2008: a review of current American Cancer Society guidelines and cancer screening issues. CA Cancer J Clin 2008;58:161-179. [Free Full Text]
  5. U. S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2008;149:185-191. [Free Full Text]
  6. Barry MJ. Why are a high overdiagnosis probability and a long lead time for prostate cancer screening so important? J Natl Cancer Inst (in press).
  7. Andriole GL, Grubb RL III, Buys SS, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009;360:1310-1319. [Free Full Text]
  8. Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360:1320-1328. [Free Full Text]
  9. Newschaffer CJ, Otani K, McDonald MK, Penberthy LT. Causes of death in elderly prostate cancer patients and in a comparison nonprostate cancer cohort. J Natl Cancer Inst 2000;92:613-621. [Free Full Text]
  10. Wilt TJ, Brawer MK, Barry MJ, et al. The Prostate cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy to watchful waiting for men with clinically localized prostate cancer. Contemp Clin Trials 2009;30:81-87. [CrossRef][ISI][Medline]
  11. Donovan J, Hamdy F, Neal D, et al. Prostate Testing for Cancer and Treatment (ProtecT) feasibility study. Health Technol Assess 2003;7:1-88. [Medline]

SIAP 2011: Cancer de mama


Cancer Mama Cat Resum ASPB 0711http://www.scribd.com/embeds/67162907/content?start_page=1&view_mode=list&access_key=key-2a2imf78s1vhp2jskn8(function() { var scribd = document.createElement(“script”); scribd.type = “text/javascript”; scribd.async = true; scribd.src = “http://www.scribd.com/javascripts/embed_code/inject.js&#8221;; var s = document.getElementsByTagName(“script”)[0]; s.parentNode.insertBefore(scribd, s); })();

Breast Cancer Screening


By Graham McMahon

The latest article in our Clinical Practice series reviews current recommendations for breast-cancer screening and thesupporting evidence, including the controversy regarding mammographic screening of women in their 40s.
Worldwide, breast cancer is now the most common cancer diagnosed in women and is the leading cause of deaths from cancer among women, with approximately 1.3 million new cases and 458,000 deaths reported in 2008.OK

Clinical Pearls

 How have the screening recommendations from the U.S. Preventive Services Task Force (USPSTF) changed in recent years?
In contrast to its 2002 guidelines, the more recent recommendations of the USPSTF, published in November 2009, support a reduction in the use of screening mammography. The two most controversial changes were the reclassification of screening for women between the ages of 40 and 49 years from a B recommendation (based on moderately strong evidence) to a C recommendation (“the decision . . . should be an individual one and take into account patient context, including the patient’s values regarding specific benefits and harms”), and the recommendation that the frequency of screening be reduced from every 1 to 2 years to every 2 years.
 What is the consensus recommendation regarding mammographic screening for women between the ages of 50 and 69?
Screening mammography for women 50 to 69 years of age is universally recommended. All but one of the trials that included women in their 60s showed a significant reduction in mortality in the screened group, although this was not true for the subgroup of women in their 50s. Still, a meta-analysis revealed significant reductions in the number of deaths in both these age groups — 14% for women in their 50s and 32% for those in their 60s.

Morning Report Questions

Q: For a 42-year-old woman with no risk factors, what are the benefits and risks of screening mammography?
A: Her chance of having invasive breast cancer over the next 8 years is about 1 in 80, and her chance of dying from it is about 1 in 400. Biennial mammographic screening will detect two out of three cancers in women her age and will reduce her risk of death from breast cancer by 15%. However, there is about a 40% chance that she will be called back for further imaging tests and a 3% chance that she will undergo biopsy, with a benign finding.
Q: What are the benefits of digital mammography?
A: The contrast between breast tumors and surrounding normal parenchyma is greater with digital mammography than with film mammography, particularly when the breast tissue is dense. In one study in which almost 50,000 asymptomatic women 40 years of age or older underwent both digital and film mammography, the two techniques were equivalent overall in sensitivity (70% and 66%, respectively) and specificity (92% for both). However, in women under the age of 50 years, digital mammography was significantly more sensitive than film (78% vs. 51%).
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Intrauterine device use, cervical infection with human papillomavirus, and risk of cervical cancer: a pooled analysis of 26 epidemiological studies


Mirena IntraUterine SystemImage via Wikipedia

The Lancet Oncology, Early Online Publication, 13 September 2011
doi:10.1016/S1470-2045(11)70223-6Cite or Link Using DOI

Intrauterine device use, cervical infection with human papillomavirus, and risk of cervical cancer: a pooled analysis of 26 epidemiological studies

Summary

Background

Intrauterine device (IUD) use has been shown to reduce the risk of endometrial cancer, but little is known about its association with cervical cancer risk. We assessed whether IUD use affects cervical human papillomavirus (HPV) infection and the risk of developing cervical cancer.

Methods

We did a pooled analysis of individual data from two large studies by the International Agency for Research on Cancer and Institut Català d’Oncologia research programme on HPV and cervical cancer; one study included data from ten case—control studies of cervical cancer done in eight countries, and the other included data from 16 HPV prevalence surveys of women from the general population in 14 countries. 2205 women with cervical cancer and 2214 matched control women without cervical cancer were included from the case—control studies, and 15 272 healthy women from the HPV surveys. Information on IUD use was obtained by personal interview. HPV DNA was tested by PCR-based assays. Odds ratios and 95% CIs were estimated using multivariate unconditional logistic regression for the associations between IUD use, cervical HPV DNA, and cervical cancer.

Findings

After adjusting for relevant covariates, including cervical HPV DNA and number of previous Papanicolaou smears, a strong inverse association was found between ever use of IUDs and cervical cancer (odds ratio 0·55, 95% CI 0·42—0·70; p<0·0001). A protective association was noted for squamous-cell carcinoma (0·56, 0·43—0·72; p<0·0001), adenocarcinoma and adenosquamous carcinoma (0·46, 0·22—0·97; p=0·035), but not among HPV-positive women (0·68, 0·44—1·06; p=0·11). No association was found between IUD use and detection of cervical HPV DNA among women without cervical cancer.

Interpretation

Our data suggest that IUD use might act as a protective cofactor in cervical carcinogenesis. Cellular immunity triggered by the device might be one of several mechanisms that could explain our findings.

Funding

Instituto de Salud Carlos III; Agència de Gestió d’Ajuts Universitaris i Recerca; Marató TV3 Foundation; Bill & Melinda Gates Foundation; International Agency for Research on Cancer; European Community; Fondo de Investigaciones Sanitarias, Spain; Preventiefonds, Netherlands; Programa Interministerial de Investigación y Desarrollo, Spain; Conselho Nacional de Desenvolvimiento Cientifico e Tecnologico, Brazil; and Department of Reproductive Health & Research, WHO.

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Nuevo metodo para cancer de prostata


Científicos en Estados Unidos crearon una prueba de orina con la cual puede detectarse de forma más precisa a los hombres que están en riesgo de cáncer de próstata.
Células de próstata cancerosas

El análisis detecta un defecto genético que causa el cáncer.

La prueba, dicen los investigadores de la Universidad de Michigan, puede ayudar a un individuo a decidir si debe someterse a una biopsia.

El análisis detecta un defecto genético, que según los científicos, muestra la presencia de la enfermedad en la mitad de los tumores de próstata.

Niveles de PSA

Actualmente para detectar los primeros signos de la enfermedad se miden los niveles del antígeno prostático específico o PSA en la sangre.
Sin embargo, estos análisis han sido controvertidos porque los niveles elevados de PSA no necesariamente significan la presencia de cáncer lo cual puede conducir a diagnósticos equivocados.
Un PSA elevado en la sangre puede mostrar la presencia de cáncer, pero también puede ser un indicio de otros trastornos, como un ensanchamiento de la próstata o una infección urinaria.
De la misma forma, una prueba normal de PSA no garantiza que un hombre no tenga un tumor, lo cual significa una oportunidad perdida para tratamiento temprano.

Pensamos que va a ser una herramienta que ayudará a los hombres con PSA elevado a decidir si necesitan una biopsia o si pueden retrasar el procedimiento

Dr. Scott Tomlins

Como el cáncer de próstata se ha convertido en el cáncer más común en los hombres y la segunda causa de muerte por cáncer en muchos países del mundo, existe una necesidad urgente de crear métodos diagnósticos más precisos.
Y desde hace tiempo varios equipos de investigadores en el mundo trabajan en el desarrollo de una prueba de orina.
La nueva prueba, creada por científicos de la Universidad de Michigan, identifica una anormalidad genética que ocurre en cerca de la mitad de todos los tumores de próstata.
En ésta dos genes cambian de lugar y se fusionan causando una mutación que, según los científicos, causa el cáncer.
Tal como señalan los investigadores en Science Translational Medicine (Science, Medicina Traslacional), los estudios llevados a cabo muestran que la fusión genética, llamada TMPRSS:ERG, “casi siempre indica la presencia de cáncer”.
Pero como este defecto sólo está presente en la mitad de los tumores prostáticos, los científicos también incluyeron en el análisis otro marcador, llamado PCA3, lo cual hace que el análisis sea más preciso.
Los científicos esperan que la prueba sea un complemento del análisis de PSA, y con ambos resultados se pueda tomar una decisión mejor informada sobre el siguiente paso, por ejemplo, si hay necesidad de someterse a una biopsia o no.
Las biopsias son pruebas invasivas e incómodas en las que es necesario introducir una aguja para extraer una muestra de tejido.
Y tampoco ofrecen un panorama completo de la glándula porque es una prueba de una muestra pequeña de la próstata, de manera que también puede dar resultados falsos.

Herramienta complementaria

Los científicos llevaron a cabo pruebas de orina con 1.300 pacientes en tres centros médicos académicos y siete hospitales del país.

Análisis de sangre

Actualmente se miden los niveles de PSA en la sangre para detectar cáncer.

Todos habían mostrado niveles elevados de PSA y habían acudido a las clínicas para someterse a una biopsia o a una prostatectomía, una cirugía para extraer parte o toda la próstata.
Los investigadores llevaron a cabo el análisis en muestras de orina de los pacientes y los dividieron en grupos de bajo, intermedio y alto riesgo de cáncer.
Posteriormente compararon esos resultados con los de las biopsias.
Encontraron que las biopsias mostraron cáncer en 21% de los pacientes del grupo de bajo riesgo, 43% de los de riesgo intermedio y 69% del grupo de alto riesgo.
La prueba de orina, sin embargo, mostró que sólo 7% de los hombres del grupo de bajo riesgo y 40% del grupo de alto riesgo tenían un tumor agresivo.
Por otra parte las pruebas de PSA mostraron que muchos hombres con PSA elevado no tenían cáncer.
Tal como señala el doctor Scott Tomlins, quien dirigió el estudio, “aquí es donde esta prueba realmente puede ayudar”.
“El análisis del TMPRSS2:ERG y PCA3 mejora significativamente la capacidad de predecir si un hombre tiene cáncer de próstata” afirma.
“Pensamos que va a ser una herramienta que ayudará a los hombres con PSA elevado a decidir si necesitan una biopsia o si pueden retrasar el procedimiento”, agrega.
Los científicos esperan que el análisis esté listo para uso en la clínica en Estados Unidos dentro de un año.

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An Avastin Recommendation & Conflicts Of Interest


Earlier this month, the National Comprehensive Cancer Network, a non-profit group of oncologists whose guidance is closely followed by leading treatment centers, voted overwhelmingly in favor of maintaining its recommendation that Avastin should be used to treat breast cancer. The vote came shortly after an FDA panel voted 6-to-0 to revoke the breast cancer indication for Avastin.
The endorsement is important because oncologists will likely continue to use Avastin even if FDA commish Margaret Hamburg rescinds the breast cancer indication. Roche and its Genentech unit had appealed a decision last December by the agency to pull the indication for their best-selling med after new studies showed the med does not prolong overall survival in breast cancer patients or provide a sufficient benefit in slowing disease progression to outweigh significant risks. This prompted the unusual two-day hearing last month (back stories here and here).
However, 10 of the 33 members of the NCCN breast cancer panel members have ties to Roche or Genentech, either as advisory board members, speakers, consultants, expert witnesses or having received clinical research support. These connections are disclosed on the NCCN web site (look here). And 25 members of the panel participated in the recent vote to maintain the recommendation.
Specifically, the NCCN panel voted 24 in favor, 0 against and 1 abstention. The simple math suggests that at least one panel member – and possibly two – with ties to Roche voted to support the metastatic breast cancer recommendation. Perhaps more panel members with connections voted, although there is now way to know ascertain this since the NCCN press release does not specify who participated in the voting.
As we have noted previously, the NCCN endorsement is likely to be a boon for Roche, since treatment for breast cancer has typically generated about $1 billion or more in annual sales. Avastin rings registers – worldwide sales last year totaled about $6.8 billion and rose 9 percent, which meant this one drug accounted for 14 percent of total Roche sales. In other words, much is at stake.
Meanwhile, the stated NCCN policy conflicts of interest requires “disclosure of external relationships and recusal of NCCN Guidelines Panel Members with conflicting interests so that the integrity of the NCCN Guidelines is not compromised or diminished by conflicts or by the perception of conflicts,” according to the NCCN web site.
The policy also states that a panel member with a significant and direct or indirect relationship with “an external entity” that constitutes a conflict shall not participate in NCCN Guidelines Panel discussions, when the panel’s action on the topic under discussion “may advantage or disadvantage an external entity.” An exception is granted when requested by the panel chair “to participate for the purpose of providing or presenting information to the NCCN Guidelines Panel.”
More specifically, certain “direct relationships,” such as a panel member who is a beneficial owner of stock in an “external” entity or a director of such an organization” would be considered to have a de facto conflict. The policy also defines “direct relationships” as anyone “who receives compensation for services including, but not limited to, management or consulting services to the organization” (here is the policy).
So we asked NCCN whether this policy was followed for the recent breast cancer panel, given that the vote tally suggested otherwise. The spokeswoman repeatedly declined to discuss specifics and referred us back to the recent press release which, again, offers no information on the topic. In fact, she refused to answer whether NCCN has a recusal policy, even though this exists on the web site. “I’m only allowed to discuss what is in the press release,” she told us over and over.
We also reached out to the 10 panel members who have ties to Roche and Genentech. One responded. Antonio Wolff wrote us to confirm that “Genentech provides funding to Johns Hopkins University (where I am employed as School of Medicine faculty) to support research costs associated with an ongoing early phase clinical trial, and I am the site PI for that study. As for your specific question regarding my activities within NCCN, I will ask (you) to contact it directly as NCCN requires all panel members to adhere to its confidentiality policy.”
And so, an influential panel with ties to a drugmaker – which has a lot of sales on the line – voted to maintain a key recommendation. In this instance, NCCN panel members fully disclosed their ties to Roche, but is this sufficient? Supposedly, there is a reason NCCN has a disclosure and recusal policy, but in this instance, there would appear to have been a breach. If none occurred, the organization should be willing to discuss specifics and defend its policy. Yet NCCN refused to do so. What do you think?
Source: Pharmalot

Better Evidence about Screening for Lung Cancer


Harold C. Sox, M.D.

June 29, 2011 (10.1056/NEJMe1103776)

In October 2010, the National Cancer Institute (NCI) announced that patients who were randomly assigned to screening with low-dose computed tomography (CT) had fewer deaths from lung cancer than did patients randomly assigned to screening with chest radiography. The first report of the NCI-sponsored National Lung Screening Trial (NLST) in a peer-reviewed medical journal appears in this issue of the Journal.1
Eligible participants were between 55 and 74 years of age and had a history of heavy smoking. They were screened once a year for 3 years and were then followed for 3.5 additional years with no screening. At each round of screening, results suggestive of lung cancer were nearly three times as common in participants assigned to low-dose CT as in those assigned to radiography, but only 2 to 7% of these suspicious results proved to be lung cancer. Invasive diagnostic procedures were few, suggesting that diagnostic CT and comparison with prior images usually sufficed to rule out lung cancer in participants with suspicious screening findings. Diagnoses of lung cancer after the screening period had ended were more common among participants who had been assigned to screening with chest radiography than among those who had been assigned to screening with low-dose CT, suggesting that radiography missed cancers during the screening period. Cancers discovered after a positive low-dose CT screening test were more likely to be early stage and less likely to be late stage than were those discovered after chest radiography. There were 247 deaths from lung cancer per 100,000 person-years of follow-up after screening with low-dose CT and 309 per 100,000 person-years after screening with chest radiography.
The conduct of the study left a little room for concern that systematic differences between the two study groups could have affected the results (internal validity). The groups had similar characteristics at baseline, and only 3% of the participants in the low-dose CT group and 4% in the radiography group were lost to follow-up. However, there were two systematic differences in adherence to the study protocol. First, as shown in Figure 1 of the article, although adherence to each screening was 90% or greater in each group, it was 3 percentage points lower for the second and third radiography screenings than for the corresponding low-dose CT screenings. Because more participants in the radiography group missed one or two screenings, the radiography group had more time in which a lung cancer could metastasize before it was detected. Second, participants in the low-dose CT group were much less likely than those in the radiography group to have a diagnostic workup after a positive result in the second and third round of screening (Table 3 of the article), which might have led to fewer screening-related diagnoses of early-stage lung cancer after low-dose CT. The potential effect of these two differences in study conduct seems to be too small to nullify the large effect of low-dose CT screening on lung-cancer mortality.
The applicability of the results to typical practice (external validity) is mixed. Diagnostic workup and treatment did take place in the community. However, the images were interpreted by radiologists at the screening center, who had extra training in the interpretation of low-dose CT scans and presumably a heavy low-dose CT workload. Moreover, trial participants were younger and had a higher level of education than a random sample of smokers 55 to 74 years of age, which might have increased adherence to the study protocol.2
Overdiagnosis is a concern in screening for cancer. Overdiagnosis occurs when a test detects a cancer that would otherwise have remained occult, either because it regressed or did not grow or because the patient died before it was diagnosed.3 In a large, randomized trial comparing two screening tests, the proportion of patients in whom cancer ultimately develops should be the same in the two study groups. A difference that persists suggests that one test is detecting cancers that would never grow large enough to be detected by the other test. Overdiagnosis is a problem because predicting which early-stage cancers will not progress is in an early stage of development,4,5 so that everyone with screen-detected cancer receives treatment that some do not need. Overdiagnosis biases case-based measures (e.g., case fatality rate) but not the population-based measures used in the NLST.
Overdiagnosis probably occurred in the NLST. After 6 years of observation, there were 1060 lung cancers in the low-dose CT group and 941 in the radiography group. Presumably, some cancers in the radiography group would have been detectable by low-dose CT but grew too slowly to be detected by radiography during the 6.5 years of observation. The report of the Mayo Lung Project provides strong evidence that radiographic screening causes overdiagnosis of lung cancer.6 At the end of the follow-up phase in the Mayo study, 46 more lung cancers were diagnosed in the group screened with radiography and sputum cytologic analysis than in the unscreened group. This gap did not close, as would be expected if undetected cancers in the unscreened group continued to grow; the gap grew and then leveled off at 69 additional lung cancers in the screened group at 12 and 16 years. The Mayo study shows that 10 to 15 additional years of follow-up will be necessary to test the hypothesis that low-dose CT in the NLST led to overdiagnosis. If the difference in the number of cancers in the two groups of the NLST persists, overdiagnosis in the low-dose CT group is the likely explanation.
The incidence of lung cancer was similar at the three low-dose CT screenings (Table 3 of the article), which implies that a negative result of low-dose CT screening did not substantially reduce the probability that the next round would detect cancer. Lung cancer was also diagnosed frequently during the 3 years of follow-up after the third low-dose CT screening. Apparently, every year, there are many lung cancers that first become detectable that year. This observation, together with the overall NLST results, suggests that continuing to screen high-risk individuals annually will provide a net benefit, at least until deaths from coexisting chronic diseases limit the gains in life expectancy from screening.
The NLST results show that three annual rounds of low-dose CT screening reduce mortality from lung cancer, and that the rate of death associated with diagnostic procedures is low. How should policy makers (those responsible for screening guidelines, practice measures, and insurance coverage) respond to this important result? According to the authors, 7 million U.S. adults meet the entry criteria for the NLST,1 and an estimated 94 million U.S. adults are current or former smokers. With either target population, a national screening program of annual low-dose CT would be very expensive, which is why I agree with the authors that policy makers should wait for more information before endorsing lung-cancer screening programs.
Policymakers should wait for cost-effectiveness analyses of the NLST data, further follow-up data to determine the amount of overdiagnosis in the NLST, and, perhaps, identification of biologic markers of cancers that do not progress.4,5 Modeling should provide estimates of the effect of longer periods of annual screening and the effect of better adherence to screening and diagnostic evaluation. Systematic reviews that include other, smaller lung-cancer screening trials will provide an overview of the entire body of evidence. Finally, it may be possible to define subgroups of smokers who are at higher or lower risk for lung cancer and tailor the screening strategy accordingly.
Individual patients at high risk for lung cancer who seek low-dose CT screening and their primary care physicians should inform themselves fully, and current smokers should also receive redoubled assistance in their attempts to quit smoking. They should know the number of patients needed to screen to avoid one lung-cancer death, the limited amount of information that can be gained from one screening test, the potential for overdiagnosis and other harms, and the reduction in the risk of lung cancer after smoking cessation. The NLST investigators report newly proven benefits to balance against harms and costs, so that physicians and patients can now have much better information than before on which to base their discussions about lung-cancer screening.
The findings of the NLST regarding lung-cancer mortality signal the beginning of the end of one era of research on lung-cancer screening and the start of another. The focus will shift to informing the difficult patient-centered and policy decisions that are yet to come.
Disclosure forms provided by the author are available with the full text of this article at NEJM.org.
This article (10.1056/NEJMe1103776) was published on June 29, 2011, at NEJM.org.

SOURCE INFORMATION

From the Department of Medicine and the Dartmouth Institute, Dartmouth Medical School, West Lebanon, NH.

REFERENCES

  1. 1
    The National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011. DOI: 10.1056/NEJMoa1102873.
  2. 2
    Baseline characteristics of participants in the randomized National Lung Screening Trial. J Natl Cancer Inst 2010;102:1771-1779
    CrossRef | Web of Science | Medline
  3. 3
    Welch HG, Black WC. Overdiagnosis in cancer. J Natl Cancer Inst 2010;102:605-613
    CrossRef | Web of Science | Medline
  4. 4
    Gauthier ML, Berman HK, Miller C, et al. Abrogated response to cellular stress identifies DCIS associated with subsequent tumor events and defines basal-like breast tumors.Cancer Cell 2007;12:479-491
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    Kerlikowske K, Molinaro AM, Gauthier ML, et al. Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis. J Natl Cancer Inst2010;102:27-37
  6. 6
    Marcus PM, Bergstrahl EJ, Zweig MH, Harris A, Offord KP, Fontana RS. Extended lung cancer incidence follow-up in the Mayo Lung Project and overdiagnosis. J Natl Cancer Inst2006;98:748-756
    CrossRef | Web of Science | Medline

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New drugs for prostate cancer


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A group of new drugs is promising to prolong the lives and relieve the symptoms of men with advanced prostate cancer, but could also add billions of dollars to the nation’s medical bills.
Bone-scan images before and after treatment with Cabozantinib. The dark spots are where cancer had spread to bones.
Multimedia
Jenny Mass
Mark Moldanado, a retired postal worker in Omaha, said that Jevtana had helped keep his cancer in check.
In the last 15 months, three new drugs that extended the lives of prostate cancer patients in clinical trials have been approved by the Food and Drug Administration and several other promising medicines are in clinical trials. Before last year, only one drug had been shown to improve survival — docetaxel, which was approved in 2004.
“What a great time it is in prostate cancer,” Dr. Daniel J. George of the Duke Cancer Institute proclaimed earlier this month at the annual meeting of the American Society of Clinical Oncology.
And it’s a great time for the drug makers, with several drugs competing to fill a niche for longer-term survival. Analysts estimate that some of the new drugs, particularly Dendreon’s Provenge and Johnson & Johnson’s Zytiga, could reach annual sales of $1 billion or even much more.
The recently approved drugs and most of those in development are for cases in which the disease has spread beyond the prostate gland and is no longer held in check by hormone therapy.
Men with that late-stage cancer had a median survival of about a year and a half using docetaxel. The new drugs each added two to five months to median survival when tested in clinical trials. Doctors say that men taking more than one of the drugs in succession would be expected to live more than two years.
But the price of these drugs has already stirred concerns about the costs of care among patients, providers and insurers. For example, Provenge costs $93,000 for a course of treatment, while Zytiga costs about $5,000 a month. Another of the new drugs, Sanofi’s Jevtana, costs about $8,000 every three weeks.
With other pricey drugs on the way, said Joel Sendek, an analyst at Lazard, “We could be talking easily $500,000 per patient or more over the course of therapy, which I don’t think the system can afford, especially since 80 percent of the patients are on Medicare.”
Medicare has already fired what some analysts interpret as a warning shot over prices, conducting a yearlong inquiry into whether to pay for Provenge. In its final decision, due Thursday, Medicare is expected to pay for the drug when used according to the label.
Medicare officials denied that price was the reason for the review. But some patient advocates and politicians portrayed the review as a step toward rationing.
Private insurers are also paying only if drugs are used according to the label, according to doctors and patient advocates.
“The reality is, there’s pushback,” said Dr. Oliver Sartor of Tulane University.
Still, for now, one company’s price is prompting the next one to follow suit.
“The pricing environment is encouraging and getting better for us,” Andrew Kay, the chief executive of Algeta, told securities analysts earlier this month, after announcing that his company’s experimental drug had extended median survival nearly three months in a clinical trial.
Mr. Kay said he had initially thought that his company, which is based in Norway, would charge about $25,000 for a typical course of treatment with the drug, Alpharadin. But with the rival drug Jevtana costing about $50,000, Algeta and its partner, Bayer, are considering a higher price.
About 218,000 men in the United States get prostate cancer each year and about 32,000 die, according to the American Cancer Society.
In many cases, the cancer is caught before it has spread beyond the prostate gland and can be cured with surgery or radiation therapy.
If the cancer has spread, men usually are given drugs, particularly Abbott Laboratories’ Lupron, that suppress the body’s production of the hormone testosterone, which can fueltumor growth.
The new drugs, for now at least, are for use when this hormone-deprivation therapy has stopped working.
“This is a small subset of people with prostate cancer,” said Dr. Charles Myers, a prostate cancer specialist in private practice in Charlottesville, Va., who is a survivor of the disease himself. However, he noted, “It’s the group of people who are dying.”
Provenge was approved in April 2010 for patients whose cancer was late-stage but not yet causing many symptoms.
Once symptoms, mainly bone pain, have appeared, men are likely to receive docetaxel, a generic drug also sold by Sanofi as Taxotere .
Two other new drugs are approved for use only after docetaxel has been tried. One, Sanofi’s Jevtana, is a chemotherapy drug in the same class as docetaxel; it was approved in June 2010. The other is Johnson & Johnson’s Zytiga, approved this April.
Many patients and doctors are most enthusiastic about Zytiga and Provenge because they are alternatives to chemotherapy, which many men want to avoid because of side effects. Provenge works by training the body’s immune system to fight the tumor.
Zytiga is a new form of hormone therapy. While Lupron mainly blocks production of testosterone by the testes, there is still some hormone produced by the adrenal gland or even by the tumor itself. Zytiga, by inhibiting an enzyme called CYP17, clamps down on testosterone production.
Doctors and patients say the new drugs can offer some men a decent quality of life, although they are not free of side effects. For instance, Zytiga, also known as abiraterone, can cause hypertension and liver damage and must be taken with the steroid prednisone.
Many men are likely to try several of the drugs. Mark Maldonado, a retired postal worker in Omaha, said that Jevtana had helped keep his cancer in check without debilitating side effects. But knowing that the drug would eventually stop working, he and his doctor “talked about abiraterone being the next step in our progress through the drugs.”
More competition is coming. Takeda Pharmaceutical and Medivation, a San Francisco company, are separately developing other drugs that block testosterone’s production or its effects.
Some of the most exciting advances, doctors say, are in the area of fighting the spread of prostate cancer to the bone. Such bone metastases are very common in men with advanced prostate cancer and account for most of the death and disability from the disease.
Cabozantinib, an experimental drug being developed by Exelixis, seems to be able to virtually eradicate bone metastases in some patients, at least as measured by bone scans, something no other drug has done.
Amgen won F.D.A. approval in November for Xgeva, a drug that reduces the risk of fractures and other problems caused by cancer in the bones. The drug can also delay the spread of cancer to the bones, according to the results of a more recent trial.
Dr. Christopher J. Logothetis, of the M. D. Anderson Cancer Center, predicted further progress.
“It’s beyond the individual drugs,” he said. “One sees a manual now on how to go forward.”

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Cervical cancer risk for women undergoing concurrent testing for human papillomavirus and cervical cytology: a population-based study in routine clinical practice


Age-standardised death rates from Cervix uteri...                                           Image via Wikipedia

The Lancet Oncology, Early Online Publication, 17 June 2011
doi:10.1016/S1470-2045(11)70145- 

Cervical cancer risk for women undergoing concurrent testing for human papillomavirus and cervical cytology: a population-based study in routine clinical practice

Summary

Background

Concurrent testing for human papillomavirus (HPV) and cervical cytology (co-testing) is an approved alternative to cytology alone in women aged 30 years and older. We aimed to assess the safety in routine clinical practice of 3-year screening intervals for women testing negative for HPV with normal cytology and to assess if co-testing can identify women at high risk of cervical cancer or cervical intraepithelial neoplasia grade 3 (CIN3) or worse over 5 years.

Methods

We assessed the 5-year cumulative incidence, starting in 2003—05, of cervical cancer and CIN3 or worse for 331 818 women aged 30 years and older who enrolled in co-testing at Kaiser Permanente Northern California (Berkeley, CA, USA) and had adequate enrolment co-test results. Follow-up continued until Dec 31, 2009. We defined cumulative incidence to include prevalence at enrolment and incidence after enrolment. Prevalence at enrolment was defined as the ratio of women diagnosed with each outcome on the biopsy visit immediately after their enrolment screening visit to the total enrolled women. At screening visits only HPV test and Pap smear samples were collected, and at biopsy visits colposcopically directed biopsies were taken. To estimate post-enrolment incidence, we used Weibull survival models.

Findings

In 315 061 women negative by HPV testing, the 5-year cumulative incidence of cancer was 3·8 per 100 000 women per year, slightly higher than for the 306 969 who were both negative by HPV and Pap testing (3·2 per 100 000), and half the cancer risk of the 319 177 who were negative by Pap testing (7·5 per 100 000). 313 465 (99·5%) women negative by HPV testing had either normal cytology or equivocal abnormalities. Abnormal cytology greatly increased cumulative incidence of CIN3 or worse over 5 years for the 16 757 positive by HPV testing (12·1% vs 5·9%; p<0·0001). By contrast, although statistically significant, abnormal cytology did not increase 5-year risk of CIN3 or worse for women negative by HPV testing to a substantial level (0·86% vs 0·16%; p=0·004). 12 208 (73%) of the women positive by HPV testing had no cytological abnormality, and these women had 258 (35%) of 747 CIN3 or worse, 25 (29%) of 87 cancers, and 17 (63%) of 27 adenocarcinomas.

Interpretation

For women aged 30 years and older in routine clinical practice who are negative by co-testing (both HPV and cytology), 3-year screening intervals were safe because a single negative test for HPV was sufficient to reassure against cervical cancer over 5 years. Incorporating HPV testing with cytology also resulted in earlier identification of women at high risk of cervical cancer, especially adenocarcinoma. Testing for HPV without adjunctive cytology might be sufficiently sensitive for primary screening for cervical cancer.

Funding

Intramural Research Program of the US National Cancer Institute/NIH/DHHS, and the American Cancer Society.

Independent Events


Age-standardised death rates from Colon and re...                       Image via WikipediaIndependent Events

I was speaking with a patient recently who was explaining why he thought that colon cancer screening with fecal occult blood testing (FOBT) was equivalent to colonoscopy. He wished to avoid colonoscopy for all the usual reasons, but also believed logically that it was not a superior test.

I won’t get into the actual evidence behind the two methods of screening; that is not an issue for this post. Instead, I want to discuss his argument. He assumed that colonoscopy had a sensitivity (probability of the test being positive in someone with a significant colon lesion) of 98%, and this figure is in the ballpark of believable numbers. Let’s assume that the sensitivity of FOBT is around 35% (also a reasonable ballpark figure). At that rate, he said, since colonoscopy is performed once every 10 years, and FOBT is performed yearly, after 10 years the performance of the two tests is similar with FOBT having a cumulative sensitivity of 99%.

There are two important problems with this argument. The first, which I will just mention in passing, is also the more obvious. If a test has to be repeated for 10 years to detect a cancer, that cancer may grow and become incurable during the testing period. Had it been found at year 1, it might have had a better chance of being cured.

The second problem is the focus of this post, and to examine it, we need to understand the calculation the patient was performing to get to a cumulative sensitivity of 99%. This is the same type of calculation that is often presented when thinking about the probability of an abnormal lab test due to chance alone in a battery of lab tests. The argument goes as follows:

We define “normal” in a lab test that has a continuous result (like serum sodium) as the range of values that captures 95% of healthy patients.
That means that 5% of healthy patients (or 1 in 20) will have an “abnormal” result on the test.
If we run a battery of different tests on a patient, each of which has a similarly defined normal range, the probability of a single abnormal result due to “chance” goes up.

The actual calculation of the likelihood of an abnormal test result typically confuses medical students and early residents until they’ve heard it presented repeatedly. A common assumption is that if there is a 1 in 20 chance of an abnormal result on each test, then if 20 tests are run there will definitely be an abnormal result. This is not the correct calculation. Under the usual assumptions that people make in thinking about this, the calculation would be that the probability of all the tests being normal is the probability of a single test being normal raised to the power of the number of tests.

Thus, for 20 tests it would be 0.95^20, which is 0.36. The probability that at least one such test will be abnormal due to “chance” is 1-0.36 or 0.64. Or, about 2/3 of normal patients would be expected to have at least one abnormal test on a battery of 20 tests under these assumptions.

So the patient utilizing FOBT for colon cancer screening was saying that, with a sensitivity of about 35%, he could expect a false negative rate of 0.65 per test but that 0.65^10 (for the ten years of testing) yielded a miss rate of 1%. This cumulative sensitivity would then be similar to that of a single colonoscopy, so why should he get the invasive procedure?

And so we come to the second problem with the patient’s argument: each round of testing is not an independent event.

The calculations I described above for cumulative probabilities make the assumption that the individual events are independent from each other. That is, the result of one test has no influence on the others.

If you flip a fair penny three times and get three heads, there is still a 1 in 2 chance that it will come up heads on the fourth flip. But if you perform FOBT once for colon cancer and it is negative it might be in the setting of your particular precancerous lesion that doesn’t tend to bleed. If so, it’s less likely to be bleeding on subsequent FOBT than an “average” lesion and so the cumulative sensitivity cannot assume independence of events. This is not just a theoretical issue: based on some research, repeated testing is thought to actually have a cumulative sensitivity of around 85%, not 99%.

So the patient was miscalculating in his decision about how to be screened for colon cancer. I actually briefly discussed this with him during the appointment, but since the real issue was that he did not want a colonoscopy he was singularly uninfluenced by the math.

This plays out in other areas as well, though:

What about that standard example above regarding batteries of lab tests that all medical students and residents are taught? The tests in the battery, too, are clearly not independent events. Normal and abnormal tests tend to cluster and so it is likely that the probability of the 20th test being abnormal in a healthy patient is affected by whether the prior 19 tests included any abnormal results.

To contrast with the assumption of probabilities in the face of independent events, here we are talking about “conditional” probabilities where we want to know the likelihood of an event given some other set of events. However, in the real world we have very few data about these situations. If, for instance, I wanted to know how likely, due to random variation, a patient with an abnormal serum sodium and chloride is to have a high serum potassium, it is extremely unlikely that I could get a high quality answer without doing my own primary research.

This problem of not knowing conditional probabilities when faced with non-independent events has an important effect on how diagnostic strategies might be misinterpreted if clinicians really started utilizing a test parameter that is a favorite in the EBM community but has not really permeated the clinical world. I’ll address this in a future post.

El cribado del cancer de prostata no se asocia a una disminucion de la mortalidad


Age-standardised death rates from Prostate can...                              Image via WikipediaConcato J, Wells CK, Horwitz RI, Penson D, Fincke G, Berlowitz DR, et al. The Effectiveness of Screening for Prostate Cancer: A Nested Case-Control Study. Arch Intern Med 2006; 166: 38-43. R TC (s) PDF (s)

Introducción

Diferentes grupos de trabajo han hecho distintas recomendaciones sobre el cribado del cáncer de próstata. A pesar de que el cribado con PSA se ha mostrado eficaz para detectar tumores de próstata asintomáticos, no se ha demostrado claramente que esta detección redunde en una reducción de la mortalidad.

Objetivo

Estudiar si el cribado del cáncer de próstata mediante determinación del PSA con o sin tacto rectal mejora la supervivencia.

Perfil del estudio

Tipo de estudio: Estudio de casos y controles
Área del estudio: Prevención
Ámbito del estudio: Comunitario
Métodos
La población de estudio estuvo formada por los pacientes varones >50 años que se visitaron entre 1989 y 1990 en cualquiera de los 10 centros del departamento de Veterans Affairs del estado de Nueva Inglaterra y que no tenían un diagnóstico de cáncer antes de 1991. Se incluyeron como casos los pacientes a los que se les diagnosticó un cáncer de próstata entre esa fecha y 1995 y que murieron antes de 2000. Para cada uno de los casos se seleccionó un control entre los pacientes que estaban vivos en la fecha de la muerte del caso hubiese sido o no diagnosticado de cáncer de próstata en ese momento ajustado por fecha de nacimiento y centro en el que se había visitado.
Un investigador que desconocía la asignación del paciente a los grupos revisaba las historias clínicas para saber si se le había hecho cribado del cáncer de próstata mediante una determinación del o tacto rectal desde 1991 hasta la fecha del diagnóstico del cáncer de próstata del caso.
La variable principal de resultado fue la muerte por cualquier causa. Como variables secundarias se utilizaron la muerte por cáncer de próstata y el cáncer de próstata progresivo.

Resultados

La figura 1 muestra el flujo de los participantes en el estudio. La edad media fue de 72 años. Entre los casos se detectó un exceso de pacientes de raza negra (10,0% frente a 4,2%; P<0,001)>

Se había llevado a cabo un cribado previo en el 14% de los casos y en el 13% de los controles. No se apreciaron diferencias estadísticamente significativas ni en la mortalidad total, ni en la mortalidad específica por cáncer de próstata ni en los análisis por subgrupos de los pacientes por edad ni en los pacientes con hipertrofia benigna de próstata (tabla 1).

OR (IC95%) P
Mortalidad total 1,08 (0,71 a 1,64) 0,72
Muerte por cáncer de próstata 1,13 (0,63 a 2,08) 0,68

Conclusiones

Los autores concluyen que los resultados de este estudio no sugieren que el cribado mediante PSA ni mediante tacto rectal reduzcan la mortalidad total ni por cáncer de próstata.

Conflictos de interés

Ninguno declarado. Financiado por una beca del Department of Veterans Affairs.

Comentario

El cribado del cáncer de próstata sigue siendo objeto de polémica. A pesar de que el PSA se ha mostrado eficaz para detectarlo, siguen existiendo dudas importantes sobre si este adelanto diagnóstico aporta más beneficios que riesgos. Desde que se ha extendido el cribado mediante PSA (sin que se haya llegado a la universalización del mismo), la probabilidad de que a un adulto se le diagnostique un cáncer de próstata casi se ha doblado. Por otro lado, la cirugía de próstata se acompaña de un elevado riesgo de disfunciones sexuales y de incontinencia. Valdría la pena pagar este precio si los beneficios en términos de mejoría del pronóstico estuviesen claros, pero los resultados de este trabajo arrojan más dudas sobre el tema.
En ausencia de datos inequívocos sobre la eficacia de una técnica de cribado provinientes de estudios de intervención, los estudios de casos y controles se han mostrado útiles para esclarecer la eficacia de algunas técnicas (como en el caso del Papanicolaou). Los autores de este trabajo han elegido como variable de respuesta principal la mortalidad total que parece una variable importante, que evita algunos de los sesgos inherentes a los estudios de prevención (sesgo del adelanto diagnóstico) y permite salvar el problema del posible error en la causa de muerte en el certificado de defunción. Un estudio de casos y controles publicado recientemente y que utilizaba como variable principal la presencia de metástasis por cáncer de próstata sí que encontró una asociación entre el cribado y un menor riesgo.
En 2009 está prevista la publicación de dos estudios de intervención, uno americano y otro europeo, que es probable que despejen las dudas actuales sobre la conveniencia de llevar a cabo o no el cribado.

Bibliografía

  1. Nelson WG, De Marzo AM, Isaacs WB. Prostate cancer. N Engl J Med 2003; 349: 366-381. TC (s) PDF (s)
  2. Barry MJ. The PSA Conundrum. Arch Intern Med 2006; 166: 7-8. TC (s) PDF (s)

Autor

Manuel Iglesias Rodal. Correo electrónico: mrodal@menta.net.

5-alpha reductase inhibitors (5-ARIs): Label Change – Increased Risk of Prostate Cancer


MedWatch logoMedWatch - The FDA Safety Information and Adverse Event Reporting Program
5-alpha reductase inhibitors (5-ARIs): Label Change – Increased Risk of Prostate Cancer
Drugs in the 5-ARI class include finasteride and dutasteride. These drugs are marketed under the brand-names Proscar, Propecia, Avodart, and Jalyn
ISSUE: FDA notified healthcare professionals that the Warnings and Precautions section of the labels for the 5-alpha reductase inhibitor (5-ARI) class of drugs has been revised to include new safety information about the increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer).
BACKGROUND: The new safety information is based on FDA’s review of two large, randomized controlled trials––the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial. Proscar, Avodart, and Jalyn are approved to improve symptoms of an enlarged prostate gland (benign prostatic hyperplasia or BPH). Proscar and Avodart are also approved to reduce the risk of urinary retention or surgery related to an enlarged prostate. Propecia is approved to treat male pattern hair loss.
RECOMMENDATION: Prior to initiating therapy with 5-ARIs, perform appropriate evaluation to rule out other urological conditions, including prostate cancer, that might mimic benign prostatic hyperplasia (BPH). See Drug Safety Communication for a Data Summary and additional information.
Healthcare professionals and patients are encouraged to report adverse events, side effects, or product quality problems related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:
  • Complete and submit the report Online:www.fda.gov/MedWatch/report.htm1
  • Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178
Read the MedWatch safety alert, including a link to the FDA Drug Safety Communication, at:

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Cancer de Mama en Argentina


Documento elaborado por el Ministerio de salud de Argentina en el año 2010.

Cancer de Mamahttp://www.scribd.com/embeds/57333690/content?start_page=1&view_mode=list&access_key=key-1q7yfyopiny39g6b348g(function() { var scribd = document.createElement(“script”); scribd.type = “text/javascript”; scribd.async = true; scribd.src = “http://www.scribd.com/javascripts/embed_code/inject.js&#8221;; var s = document.getElementsByTagName(“script”)[0]; s.parentNode.insertBefore(scribd, s); })();

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Revisiones sobre el efecto de la aspirina en la mortalidad por cáncer


Revisiones sobre el efecto de la aspirina en la mortalidad por cáncer

Bosetti C, Gallus S, La Vecchia CAspirin and cancer risk: an updated quantitative review to 2005. Cancer Causes Control 2006; 17: 871-888.    TC (s)   PDF (s)
En esta revisión se incluyeron todos los estudios observacionales sobre el cáncer que incluían información sobre aspirina y AINE publicados hasta 2005. Se identificaron 82 estudios. Los resultados se resumen en la tabla A.
Tabla 1. RR de desarrollar un cáncer en relación con la toma de aspirina en estudios observacionales.
Tipo de estudio n RR combinado (IC95%)
Colorrectal Casos y controles 12 0,59 (0,54 a 0,64) 0,71 (0,67 a 0,75)
Cohortes 8 0,85 (0,78 a 0,92)
Esófago Casos y controles 2 0,41 (0,29 a 0,57) 0,72 (0,62 a 0,84)
Cohortes 4 0,83 (0,70 a 0,98)
Estómago Casos y controles 3 0,67 (0,56 a 0,80) 0,84 (0,76 a 0,93)
Cohortes 4 0,93 (0,82 a 1,05)
Páncreas Casos y controles 1 1,00 (0,72 a 1,39) 0,96 (0,92 a 1,01)
Cohortes 4 0,96 (0,92 a 1,01)
Pulmón Casos y controles 2 0,70 (0,56 a 0,88) 0,94 (0,89 a 1,00)
Cohortes 6 0,96 (0,91 a 1,02)
Mama Casos y controles 7 0,80 (0,73 a 0,87) 0,90 (0,87 a 0,94)
Cohortes 12 0,94 (0,90 a 0,98)
Ovario Casos y controles 6 0,82 (0,69 a 0,99) 0,89 (0,78 a 1,02)
Cohortes 2 0,98 (0,80 a 1,20)
Próstata Casos y controles 5 1,02 (0,90 a 1,16) 0,98 (0,95 a 1,01)
Cohortes 10 0,97 (0,94 a 1,01)
Vejiga Casos y controles 1 0,85 (0,66 a 1,09) 0,95 (0,77 a 1,17)
Cohortes 3 1,23, (0,83 a 1,81)
Riñón Casos y controles 5 1,21 (1,07 a 1,36) 1,22 (1,08 a 1,37)
Cohortes 3 1,45 (0,87 a 2,40)
Linfoma no Hodgkin Casos y controles 4 0,98 (0,85 a 1,14) 1,00 (0,88 a 1,14)
Cohortes 2 1,08 (0,78 a 1,51)
Rothwell PM, Wilson M, Elwin CE, Norrving B, Algra A, Warlow CP, Meade TWLong-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 2010; 376: 1741-1750.    TC (s)   PDF (s)
En esta revisión sistemática se incluyeron los ensayos clínicos con una mediana de seguimiento superior a los 4 años en los que se comparaba el efecto de la aspirina tomada diariamente con un grupo control (la mayoría llevados a cabo en un contexto de prevención de las enfermedades cardiovasculares). La variable de resultado principal fue la mortalidad por diferentes tipos de tumores, así como su repercusión sobre la mortalidad total.
Se incluyeron 8 estudios con datos de 25.570 individuos entre los que se registraron 674 muertes por cáncer. Dos estudios se llevaron a cabo en población general y los otros 6 en pacientes con enfermedad cardiovascular conocida o de alto riesgo para desarrollarla. Tres de los estudios ofrecían datos de seguimiento a largo plazo una vez concluido el ensayo clínico.
Se observó una menor mortalidad por cáncer en las personas asignadas al grupo de tratamiento con aspirina respecto al control (HR 0,82; IC95% 0,70 a 0,95; P=0,01), que fue superior para periodos de seguimiento > 5 años (tabla 2). Esta reducción fue principalmente a expensas de los tumores digestivos y otros tumores sólidos, como los de pulmón y próstata.
* Basado en 3 estudios.

Tabla 2Hazard ratio (IC95%) de muerte por diferentes tipos de cáncer en función del periodo de seguimiento.
Seguimiento (años) 0-5 >5 10-20*
Esófago 0,78 (0,27 a 2,23) 0,43 (0,11 a 1,72) 0,36 (0,18 a 0,71)
Páncreas 0,88 (0,44 a 1,77) 0,25 (0,07 a 0,92) 0,79 (0,44 a 1,42)
Colorrectal 0,78 (0,39 a 1,56) 0,41 (0,17 a 1,00) 0,51 (0,35 a 0,74)
Estómago 1,85 (0,81 a 4,23) 3,09 (0,64 a 14,91) 0,42 (0,23 a 0,79)
Pulmón 0,92 (0,65 a 1,30) 0,68 (0,42 a 1,10) 0,75 (0,55 a 1,02)
Próstata 0,70 (0,29 a 1,73) 0,52 (0,20 a 1,34) 0,80 (0,58 a 1,09)
Todos 0,88 (0,72 a 1,06) 0,62 (0,47 a 0,82) 0,77 (0,67 a 0,89)
El efecto sobre los tumores sólidos no digestivos aumentaba con la edad. No se encontraron diferencias entre los fumadores y los no fumadores. Los adenocarcinomas parecían ser el tipo de tumores que se beneficiaban más de la intervención. Se apreció una reducción de la mortalidad total a los 15 años de seguimiento debida a la reducción de mortalidad por cáncer (HR 0,92; 0,86 a 0,99; p=0,03), que no se mantuvo a los 20 años (HR 0,96; IC95% 0,90 a 1,02; P=0,37). No se encontraron diferencias con dosis de aspirina por encima de los 75 mg/d.

Riesgo de hemorragia asociado a la toma de aspirina

Derry S, Loke YKRisk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ 2000; 321: 1183-1187.    TC   PDF
En esta revisión sistemática se incluyeron los ensayos clínicos aleatorios con >100 individuos incluidos en los que uno de los brazos del estudio era la toma de aspirina y el otro placebo o la ausencia de tratamiento con una duración de >12 meses que ofrecían datos sobre el número de hemorragias digestivas que se dieron en ambos grupos.
Se detectaron 24 estudios que cumplían los criterios de inclusión con 65.987 participantes de edad media y un seguimiento medio de 28 meses. Las dosis utilizadas fueron de 50-1.500 mg/d. El 74% eran varones. Se dieron hemorragias digestivas en el 2,47% de los individuos asignados al grupo aspirina y un 1,42% de los asignados al grupo placebo, con una odds ratio de 1,68 (IC95% 1,58 a 1,88). El NNH durante 28 meses fue de 106 pacientes. Esta relación se mantuvo incluso para dosis bajas de aspirina. En los pacientes asignados a tomar 50-162,5 mg/d de aspirina, se dieron hemorragias digestivas en el 2,3% de los pacientes asignados al grupo de tratamiento activo frente a un 1,45% de los asignados al grupo placebo (OR 1,59; IC95% 1,40 a 1,81; P < 0.0001).
Laine LReview article: gastrointestinal bleeding with low-dose aspirin – what´s the risk?. Aliment Pharmacol Ther 2006; 24: 897-908.    TC   PDF
En un metaanálisis que incluyó 14 ensayos clínicos que comparaban el tratamiento con aspirina a dosis bajas con placebo, con 57.000 pacientes seguidos durante 12-76 meses, el riesgo relativo de hemorragia importante (que ocasionase la muerte o requiriese ingreso o transfusión) fue de 2,07 (IC95% 1,61 a 2,66). En términos absolutos representa un exceso del 0,12% anual (NNH 833 pacientes). En un estudio de cohortes que incluyó casi 500.000 personas se observó un riesgo relativo de ingreso por HDA de 2,6 (IC95% 2,2 a2,9). En los estudios de casos y controles publicados, la odds ratio observada osciló entre 1,3 y 3,2.

Recomendaciones de grupos de trabajo

Cuzick J, Otto F, Baron JA, Brown PH, Burn J, Greenwald P et alAspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Lancet 2009; 10: 501-507.    TC (s)   PDF (s)
En 2009, en el seno de la V International Conference on Cancer Prevention se llevó a cabo una reunión monográfica para examinar la relación entre la aspirina y los AINE y el cáncer. A pesar de que concluyeron que había numerosos indicios sobre que la aspirina y los AINE podían prevenir el desarrollo del cáncer colorrectal y probablemente del de otras localizaciones, decidieron no emitir ninguna recomendación práctica para la clínica debido a las numerosas incertidumbres existentes, como la dosis mínima efectiva y la duración del tratamiento recomendables, los subgrupos que podrían beneficiarse más del tratamiento y el balance riesgo-beneficio de un tratamiento de este tipo. Por lo tanto, recomiendan llevar a cabo ensayos clínicos enfocados a la quimioprevención del cáncer.
U.S. Preventive Services Task ForceRoutine Aspirin or Nonsteroidal Anti-inflammatory Drugs for the Primary Prevention of Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 2007; 146: 361-364.    TC   PDF
En la última recomendación emitida por la USPSTF sobre el tema, los autores concluyen que las pruebas sobre los efectos adversos de la aspirina los AINE son más consistentes que las de sus efectos preventivos sobre el cáncer de colon, por lo que recomendaban en contra de la utilización de estas sustancias con esta finalidad. Hay que matizar que la recomendación sólo hace referencia al cáncer colorrectal en la población general.

Artículos de opinión

Moayyedi P, Jankowski JADoes long term aspirin prevent cancer?. BMJ 2011; 342: c7326.   TC (s)   PDF (s)
En este reciente editorial los autores revisan los trabajos publicados y llegan a la conclusión que, aunque es probable que la aspirina sea eficaz en la prevención de las muertes por cáncer, la reducción en términos absolutos es pequeña, por lo que no se compensen los riesgos de un tratamiento con esta sustancia a largo plazo. Insisten en que los metaanálsis de estudios que han valorado el efecto sobre la mortalidad total a largo plazo muestran unas diferencias marginalmente significativas, por lo que pueden ser muy sensibles a los sesgos de los estudios derivados de la inclusión o exclusión de determinados trabajos. Recomiendan esperar a la publicación de los resultados del estudio AspECT, en el que se analiza el efecto preventivo de la aspirina sobre el esófago de Barret y la mortalidad total, cuyos resultados preliminares se deben publicar el año próximo, antes de hacer una recomendación a la población general.
Jacobs EJWill an aspirin a day help keep fatal cancer away?. Lancet 2011; 377: 3-4.   TC (s)   PDF (s)
En este otro editorial en el que se comentan los resultados del trabajo de Rothwell y colaboradores, los autores hacen hincapié en el hecho de que en el seguimiento a largo plazo (más allá de los primeros 5 años) la reducción de la mortalidad por cáncer observada era del 34%. Sin embargo, comentan que dado que el efecto beneficioso se debe únicamente a determinados tipos de tumores (colon, esófago, estómago, próstata y pulmón) es posible que los beneficios potenciales no se repartan por igual en toda la población. Por ejemplo, es probable que se beneficie más un varón de 50 años fumador que una mujer de la misma edad no fumadora a la que se le ha hecho un cribado del cáncer de colon con resultados negativos.

Conclusiones

Tras la publicación del metaanálisis de Rothwell sobre la disminución del riesgo de muerte por cáncer en los pacientes tratados con aspirina se ha reabierto el debate sobre la posibilidad de utilizar esta sustancia o los AINE en la prevención de este grupo de enfermedades. A pesar de que  existen numerosas pruebas sobre la probable eficacia de estas sustancias, derivadas tanto de estudios experimentales, como observacionales y de ensayos clínicos, no está claro el balance riesgo-beneficio de este tratamiento. Hay que tomar en consideración además que introducir la aspirina en determinados grupos de edad puede suponer la necesidad de añadir tratamientos antisecretores para la prevención de la gastropatía por AINE, que también tienen efectos indeseables a largo plazo. Además quedan por aclarar aspectos prácticos importantes para poder llevar a cabo una recomendación, como serían la población diana y la dosis y la duración del tratamiento recomendados.
Por lo tanto, las pruebas disponibles hasta el momento abren una posibilidad teórica interesante, pero para despejar las dudas será conveniente esperar los resultados de ensayos clínicos en los que se estudie la utilidad de la aspirina para esta indicación.
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Antigeno Prostatico Especifico: inutil para el cribado de cancer de prostata


Todavia desconozco en que idioma hay que escribir esto, pero por enesima  vez sale otro articulo que dice que la PSA,  no tiene ninguna utilidad en el cribado de cáncer de próstata y que sólo sirve para el seguimiento de pacientes con Cáncer de prostata. El tema es simple. Se trata de una prueba inespecifica, y el famoso antigeno es volumen-dependiente del tamaño de la prostata. Por ende, en la natural evolucion que tenemos los hombres la prostata se agranda con la edad. Por tanto, ningun valor sirve para diferenciar si ese agrandamiento se  debió a la hipertrofia prostática benigna, que también es muy común luego de los 65 años. Por otro lado, un viejo anatomista,  Testut, ya escribia en su tratado que data del año 1900, que en sus autopsias encontraba un 100% de cáncer de prostata en hombres  mayores de 80 años. En otras palabras, y aunque los urólogos se empeñen en poner al cancer de próstata como un grave problema de salud, colocandolo entre las primeras causas de muerte, la realidad indica, que nos morimos más con cáncer de próstata que por el cáncer mismo. Por ende es un buen marcador de la evolución del cáncer pero no tiene ninguna utilidad, escrito en Inglés (también ha sido escrito en castellano, catalán, portugues, francés, ruso, y seguramente en esperanto) por el  British Medical Journal.
Por ende tendremos que seguir lidiando con los expertos que aparecen en la prensa de todo el mundo, e intentan convencer a la gente de hacerse estos estudios desde los 50 años. 

Utilizando una cohorte grande Seuca relacionada con un registro nacional de cáncer, los investigadores compararon los valores iniciales de PSA de aquellos que desarrollaron cáncer de próstata en el curso de 7 años post escrutinio, con otros hombres de similares características que no desarrollaron cáncer de próstata. La sobreposición de los valores de PSA frustraron los esfuerzos de los investigadores de encontrar un valor que tenga alta especificidad así como una sensibilidad del 50%. Sin embargo, notaron que un valor de PSA menor de 1 ng/mL virtualmente descarta el diagnóstico durante el período de seguimiento.

Debido a los resultados de este estudio, se podría decir que los datos sobre los costos y beneficios de las pruebas de PSA permanecen insuficientes para apoyar el escrutinio masivo.

Referencia: Benny Holmström, et al. Prostate specific antigen for early detection of prostate cancer: longitudinal study. BMJ. Septiembre 2009;339:b3537.

Cancer Managment: a multidisciplinary Approach


Medical, Surgical & Radiation Oncology

Edited by: 
Richard Pazdur, MD 
Office of Oncology Drug Products
Center for Drug Evaluation and Research
US Food and Drug Administration

Lawrence R. Coia, MD
Southern Ocean County Radiation Oncology 
Manahawkin, New Jersey

William J. Hoskins, MD
Curtis and Elizabeth Anderson Cancer Institute
Memorial Health University Medical Center
Savannah, Georgia

Lawrence D. Wagman, MD
Division of Surgery
City of Hope National Medical Center
Duarte, California 

And the publishers of the journal ONCOLOGY 

      CMHB Cover
Preface 
Richard Pazdur, Lawrence R. Coia, William J. Hoskins, and Lawrence D. Wagman
About This Treatment Guide 
Content provided in this 10th edition was released in June 2007. New clinical data announced since that time will be included in an updated 11th edition of “Cancer Management: A Multidisciplinary Approach,” coming soon.

Principles of Multidisciplinary Therapy

Chapter 2: Principles of Radiation Therapy 
Michael J. Gazda and Lawrence R. Coia
Chapter 3: Principles of Oncologic Pharmacotherapy 
Chris H. Takimoto and Emiliano Calvo 

Cancers of the Head and Neck Region

Chapter 4: Head and Neck Tumors 
John Andrew Ridge, Bonnie S. Glisson, Eric M. Horwitz, and Miriam N. Lango
Chapter 5: Thyroid and Parathyroid Cancers 
Gilbert G. Fareau, Rena Vassilopoulou-Sellin, Robert Lustig, and Jeffrey P. Lamont

Lung Cancer

Chapter 6: Non–Small-Cell Lung Cancer 
Benjamin Movsas, Fadlo R. Khuri, and Kemp Kernstine
Chapter 7: SCLC, Mesothelioma, Thymoma 
Bonnie S. Glisson, Benjamin Movsas, and Walter Scott

Breast Cancer

Chapter 8: Breast Cancer Overview
Lori Jardines, Bruce G. Haffty, Paul Fisher, Jeffrey Weitzel, and Melanie Royce
Chapter 9: Stages 0 and I Breast Cancer
Lori Jardines, Bruce G. Haffty, and Melanie Royce
Chapter 10: Stage II Breast Cancer
Lori Jardines, Bruce G. Haffty, and Melanie Royce
Chapter 11: Stages III and IV Breast Cancer
Lori Jardines, Bruce G. Haffty, Melanie Royce, and Ishmael Jaiyesimi

Gastrointestinal Cancers

Chapter 12: Esophageal Cancer
I. Benjamin Paz, Jimmy J. Hwang, and Rajesh Iyer 
Chapter 13: Gastric Cancer
Charles D. Blanke, Lawrence R. Coia, and Roderich E. Schwarz 
Chapter 14: Pancreatic, Neuroendocrine GI, and Adrenal Cancers
Al B. Benson III, Robert J. Myerson, and John Hoffman 
Chapter 15: Liver, Gallbladder, & Biliary Tract Cancers
Lawrence D. Wagman, John M. Robertson, and Bert O’Neil 
Chapter 16: Colon, Rectal, and Anal Cancers
Joshua D. I. Ellenhorn, Carey A. Cullinane, Lawrence R. Coia, and Steven R. Alberts

Genitourinary Malignancies

Chapter 17: Prostate Cancer
Judd W. Moul, Brent K. Hollenbeck, Kathleen W. Beekman, Joseph Lattanzi, and Maha Hussain
Chapter 18: Testicular Cancer
Patrick J. Loehrer, Thomas E. Ahlering, Mark Buyyounouski, and Douglas Skarecky
Chapter 19: Urothelial & Kidney Cancers
Bruce G. Redman, Mark Hurwitz, Philippe E. Spiess, and Louis L. Pisters

Gynecologic Malignancies

Chapter 20: Cervical Cancer
Dennis S. Chi, Carlos A. Perez, Rachelle M. Lanciano, and John Kavanagh
Chapter 21: Uterine Corpus Tumors
Kathryn M. Greven, Maurie Markman, and David Scott Miller
Chapter 22: Ovarian Cancer
Stephen C. Rubin and Paul Sabbatini

Skin Cancers

Chapter 23: Melanoma & Other Skin Cancers
Eric H. Jensen, Kim A. Margolin, and Vernon K. Sondak 
The ABCDs of moles and melanomas 

Sarcomas

Chapter 24: Bone Sarcomas
Alan W. Yasko and Warren Chow
Chapter 25: Soft-tissue Sarcomas
Peter W. T. Pisters, Mitchell Weiss, Robert Maki, and Gary N. Mann

Brain Tumors

Chapter 26: Primary and Metastatic Brain Tumors
Lisa M. DeAngelis, Jay S. Loeffler, and Adam N. Mamelak

Other Solid Tumors

Chapter 27: AIDS-related Malignancies
Ronald T. Mitsuyasu and Jay S. Cooper
Chapter 28: Carcinoma of an Unknown Primary Site
John D. Hainsworth and Lawrence M. Weiss

Hematologic Malignancies

Chapter 29: Hodgkin Lymphoma
Joachim Yahalom and David Straus
Chapter 30: Non-Hodgkin Lymphoma
Steven T. Rosen, Jane N. Winter, Leo I. Gordon, Andrew M. Evens, and Nicos Nicolaou
Chapter 31: Multiple Myeloma and Other Plasma Cell Dyscrasias
Sundar Jagannath, Paul Richardson, and Nikhil C. Munshi
Chapter 32: Acute Leukemias
Margaret R. O’Donnell
Chapter 33: Chronic Myelogenous Leukemia
Jorge E. Cortes, Richard T. Silver, and Hagop Kantarjian
Chapter 34: Chronic Lymphocytic Leukemia
William G. Wierda, Nicole Lamanna, Jorge E. Cortes, and Mark A. Weiss
Chapter 35: Myelodysplastic Syndromes
Jorge E. Cortes, Alan List, and Hagop Kantarjian

Palliative and Supportive Care

Chapter 37: Pain Management
Sharon M. Weinstein, Penny R. Anderson, Alan W. Yasko, and Lawrence Driver
Chapter 38: Management of Nausea and Vomiting
Steven M. Grunberg and Marisa Siebel
Chapter 40: Hematopoietic Growth Factors
Sally Yowell Barbour and Jeffrey Crawford
Chapter 41: Fatigue and Dyspnea
Sriram Yennurajalingam and Eduardo Bruera
Chapter 42: Anorexia and Cachexia
Charles Loprinzi and Aminah Jatoi

Complications

Chapter 45: Oncologic Emergencies
Carmen P. Escalante, Ellen Manzullo, and Mitchell Weiss
Chapter 47: Fluid Complications
Frederic W. Grannis, Jr., Carey A. Cullinane, and Lily Lai

Appendices

Cancer Managment: a multidisciplinary Approach


Medical, Surgical & Radiation Oncology

Edited by: 
Richard Pazdur, MD 
Office of Oncology Drug Products
Center for Drug Evaluation and Research
US Food and Drug Administration

Lawrence R. Coia, MD
Southern Ocean County Radiation Oncology 
Manahawkin, New Jersey

William J. Hoskins, MD
Curtis and Elizabeth Anderson Cancer Institute
Memorial Health University Medical Center
Savannah, Georgia

Lawrence D. Wagman, MD
Division of Surgery
City of Hope National Medical Center
Duarte, California 

And the publishers of the journal ONCOLOGY 

      CMHB Cover
Preface 
Richard Pazdur, Lawrence R. Coia, William J. Hoskins, and Lawrence D. Wagman
About This Treatment Guide 
Content provided in this 10th edition was released in June 2007. New clinical data announced since that time will be included in an updated 11th edition of “Cancer Management: A Multidisciplinary Approach,” coming soon.

Principles of Multidisciplinary Therapy

Chapter 2: Principles of Radiation Therapy 
Michael J. Gazda and Lawrence R. Coia
Chapter 3: Principles of Oncologic Pharmacotherapy 
Chris H. Takimoto and Emiliano Calvo 

Cancers of the Head and Neck Region

Chapter 4: Head and Neck Tumors 
John Andrew Ridge, Bonnie S. Glisson, Eric M. Horwitz, and Miriam N. Lango
Chapter 5: Thyroid and Parathyroid Cancers 
Gilbert G. Fareau, Rena Vassilopoulou-Sellin, Robert Lustig, and Jeffrey P. Lamont

Lung Cancer

Chapter 6: Non–Small-Cell Lung Cancer 
Benjamin Movsas, Fadlo R. Khuri, and Kemp Kernstine
Chapter 7: SCLC, Mesothelioma, Thymoma 
Bonnie S. Glisson, Benjamin Movsas, and Walter Scott

Breast Cancer

Chapter 8: Breast Cancer Overview
Lori Jardines, Bruce G. Haffty, Paul Fisher, Jeffrey Weitzel, and Melanie Royce
Chapter 9: Stages 0 and I Breast Cancer
Lori Jardines, Bruce G. Haffty, and Melanie Royce
Chapter 10: Stage II Breast Cancer
Lori Jardines, Bruce G. Haffty, and Melanie Royce
Chapter 11: Stages III and IV Breast Cancer
Lori Jardines, Bruce G. Haffty, Melanie Royce, and Ishmael Jaiyesimi

Gastrointestinal Cancers

Chapter 12: Esophageal Cancer
I. Benjamin Paz, Jimmy J. Hwang, and Rajesh Iyer 
Chapter 13: Gastric Cancer
Charles D. Blanke, Lawrence R. Coia, and Roderich E. Schwarz 
Chapter 14: Pancreatic, Neuroendocrine GI, and Adrenal Cancers
Al B. Benson III, Robert J. Myerson, and John Hoffman 
Chapter 15: Liver, Gallbladder, & Biliary Tract Cancers
Lawrence D. Wagman, John M. Robertson, and Bert O’Neil 
Chapter 16: Colon, Rectal, and Anal Cancers
Joshua D. I. Ellenhorn, Carey A. Cullinane, Lawrence R. Coia, and Steven R. Alberts

Genitourinary Malignancies

Chapter 17: Prostate Cancer
Judd W. Moul, Brent K. Hollenbeck, Kathleen W. Beekman, Joseph Lattanzi, and Maha Hussain
Chapter 18: Testicular Cancer
Patrick J. Loehrer, Thomas E. Ahlering, Mark Buyyounouski, and Douglas Skarecky
Chapter 19: Urothelial & Kidney Cancers
Bruce G. Redman, Mark Hurwitz, Philippe E. Spiess, and Louis L. Pisters

Gynecologic Malignancies

Chapter 20: Cervical Cancer
Dennis S. Chi, Carlos A. Perez, Rachelle M. Lanciano, and John Kavanagh
Chapter 21: Uterine Corpus Tumors
Kathryn M. Greven, Maurie Markman, and David Scott Miller
Chapter 22: Ovarian Cancer
Stephen C. Rubin and Paul Sabbatini

Skin Cancers

Chapter 23: Melanoma & Other Skin Cancers
Eric H. Jensen, Kim A. Margolin, and Vernon K. Sondak 
The ABCDs of moles and melanomas 

Sarcomas

Chapter 24: Bone Sarcomas
Alan W. Yasko and Warren Chow
Chapter 25: Soft-tissue Sarcomas
Peter W. T. Pisters, Mitchell Weiss, Robert Maki, and Gary N. Mann

Brain Tumors

Chapter 26: Primary and Metastatic Brain Tumors
Lisa M. DeAngelis, Jay S. Loeffler, and Adam N. Mamelak

Other Solid Tumors

Chapter 27: AIDS-related Malignancies
Ronald T. Mitsuyasu and Jay S. Cooper
Chapter 28: Carcinoma of an Unknown Primary Site
John D. Hainsworth and Lawrence M. Weiss

Hematologic Malignancies

Chapter 29: Hodgkin Lymphoma
Joachim Yahalom and David Straus
Chapter 30: Non-Hodgkin Lymphoma
Steven T. Rosen, Jane N. Winter, Leo I. Gordon, Andrew M. Evens, and Nicos Nicolaou
Chapter 31: Multiple Myeloma and Other Plasma Cell Dyscrasias
Sundar Jagannath, Paul Richardson, and Nikhil C. Munshi
Chapter 32: Acute Leukemias
Margaret R. O’Donnell
Chapter 33: Chronic Myelogenous Leukemia
Jorge E. Cortes, Richard T. Silver, and Hagop Kantarjian
Chapter 34: Chronic Lymphocytic Leukemia
William G. Wierda, Nicole Lamanna, Jorge E. Cortes, and Mark A. Weiss
Chapter 35: Myelodysplastic Syndromes
Jorge E. Cortes, Alan List, and Hagop Kantarjian

Palliative and Supportive Care

Chapter 37: Pain Management
Sharon M. Weinstein, Penny R. Anderson, Alan W. Yasko, and Lawrence Driver
Chapter 38: Management of Nausea and Vomiting
Steven M. Grunberg and Marisa Siebel
Chapter 40: Hematopoietic Growth Factors
Sally Yowell Barbour and Jeffrey Crawford
Chapter 41: Fatigue and Dyspnea
Sriram Yennurajalingam and Eduardo Bruera
Chapter 42: Anorexia and Cachexia
Charles Loprinzi and Aminah Jatoi

Complications

Chapter 45: Oncologic Emergencies
Carmen P. Escalante, Ellen Manzullo, and Mitchell Weiss
Chapter 47: Fluid Complications
Frederic W. Grannis, Jr., Carey A. Cullinane, and Lily Lai

Appendices

USPSTF: Guia para cribado de cancer de colon


right arrow U.S. Preventive Services Task Force* 

4 November 2008 | Volume 149 Issue 9

Description: Update of the 2002 U.S. Preventive Services Task Force (USPSTF) recommendation statement on screening for colorectal cancer.

Methods: In order to update its recommendation, the USPSTF commissioned 2 studies: 1) a targeted systematic evidence review on 4 selected questions relating to test characteristics andbenefits and harms of screening technologies; and 2) a decision analytic modeling analysis using population modeling techniques to compare the expected health outcomes and resource requirements of available screening modalities when used in a programmatic way over time.

Recommendations: The USPSTF recommends screening for colorectal cancer using fecal occult blood testing, sigmoidoscopy, or colonoscopy in adults, beginning at age 50 years and continuing until age 75 years. The risks and benefits of these screening methods vary. (A recommendation.)

The USPSTF recommends against routine screening for colorectal cancer in adults 76 to 85 years of age. There may be considerations that support colorectal cancer screening in an individual patient. (C recommendation.)

The USPSTF recommends against screening for colorectal cancer in adults older than age 85 years. (D recommendation.)

The USPSTF concludes that the evidence is insufficient to assess the benefits and harms of computed tomographic colonographyand fecal DNA testing as screening modalities for colorectal cancer. (I statement.)

USPSTF: Guia para cribado de cancer de colon


right arrow U.S. Preventive Services Task Force* 

4 November 2008 | Volume 149 Issue 9

Description: Update of the 2002 U.S. Preventive Services Task Force (USPSTF) recommendation statement on screening for colorectal cancer.

Methods: In order to update its recommendation, the USPSTF commissioned 2 studies: 1) a targeted systematic evidence review on 4 selected questions relating to test characteristics andbenefits and harms of screening technologies; and 2) a decision analytic modeling analysis using population modeling techniques to compare the expected health outcomes and resource requirements of available screening modalities when used in a programmatic way over time.

Recommendations: The USPSTF recommends screening for colorectal cancer using fecal occult blood testing, sigmoidoscopy, or colonoscopy in adults, beginning at age 50 years and continuing until age 75 years. The risks and benefits of these screening methods vary. (A recommendation.)

The USPSTF recommends against routine screening for colorectal cancer in adults 76 to 85 years of age. There may be considerations that support colorectal cancer screening in an individual patient. (C recommendation.)

The USPSTF recommends against screening for colorectal cancer in adults older than age 85 years. (D recommendation.)

The USPSTF concludes that the evidence is insufficient to assess the benefits and harms of computed tomographic colonographyand fecal DNA testing as screening modalities for colorectal cancer. (I statement.)

El cribado del cancer de prostata no se asocia a una disminucion de la mortalidad


Concato J, Wells CK, Horwitz RI, Penson D, Fincke G, Berlowitz DR, et al. The Effectiveness of Screening for Prostate Cancer: A Nested Case-Control Study. Arch Intern Med 2006; 166: 38-43. R TC (s) PDF (s)

Introducción

Diferentes grupos de trabajo han hecho distintas recomendaciones sobre el cribado del cáncer de próstata. A pesar de que el cribado con PSA se ha mostrado eficaz para detectar tumores de próstata asintomáticos, no se ha demostrado claramente que esta detección redunde en una reducción de la mortalidad.

Objetivo

Estudiar si el cribado del cáncer de próstata mediante determinación del PSA con o sin tacto rectal mejora la supervivencia.

Perfil del estudio

Tipo de estudio: Estudio de casos y controles

Área del estudio: Prevención

Ámbito del estudio: Comunitario

Métodos

La población de estudio estuvo formada por los pacientes varones >50 años que se visitaron entre 1989 y 1990 en cualquiera de los 10 centros del departamento de Veterans Affairs del estado de Nueva Inglaterra y que no tenían un diagnóstico de cáncer antes de 1991. Se incluyeron como casos los pacientes a los que se les diagnosticó un cáncer de próstata entre esa fecha y 1995 y que murieron antes de 2000. Para cada uno de los casos se seleccionó un control entre los pacientes que estaban vivos en la fecha de la muerte del caso hubiese sido o no diagnosticado de cáncer de próstata en ese momento ajustado por fecha de nacimiento y centro en el que se había visitado.

Un investigador que desconocía la asignación del paciente a los grupos revisaba las historias clínicas para saber si se le había hecho cribado del cáncer de próstata mediante una determinación del o tacto rectal desde 1991 hasta la fecha del diagnóstico del cáncer de próstata del caso.

La variable principal de resultado fue la muerte por cualquier causa. Como variables secundarias se utilizaron la muerte por cáncer de próstata y el cáncer de próstata progresivo.

Resultados

La figura 1 muestra el flujo de los participantes en el estudio. La edad media fue de 72 años. Entre los casos se detectó un exceso de pacientes de raza negra (10,0% frente a 4,2%; P

Se había llevado a cabo un cribado previo en el 14% de los casos y en el 13% de los controles. No se apreciaron diferencias estadísticamente significativas ni en la mortalidad total, ni en la mortalidad específica por cáncer de próstata ni en los análisis por subgrupos de los pacientes por edad ni en los pacientes con hipertrofia benigna de próstata (tabla 1).

OR (IC95%) P
Mortalidad total 1,08 (0,71 a 1,64) 0,72
Muerte por cáncer de próstata 1,13 (0,63 a 2,08) 0,68

Conclusiones

Los autores concluyen que los resultados de este estudio no sugieren que el cribado mediante PSA ni mediante tacto rectal reduzcan la mortalidad total ni por cáncer de próstata.

Conflictos de interés

Ninguno declarado. Financiado por una beca del Department of Veterans Affairs.

Comentario

El cribado del cáncer de próstata sigue siendo objeto de polémica. A pesar de que el PSA se ha mostrado eficaz para detectarlo, siguen existiendo dudas importantes sobre si este adelanto diagnóstico aporta más beneficios que riesgos. Desde que se ha extendido el cribado mediante PSA (sin que se haya llegado a la universalización del mismo), la probabilidad de que a un adulto se le diagnostique un cáncer de próstata casi se ha doblado. Por otro lado, la cirugía de próstata se acompaña de un elevado riesgo de disfunciones sexuales y de incontinencia. Valdría la pena pagar este precio si los beneficios en términos de mejoría del pronóstico estuviesen claros, pero los resultados de este trabajo arrojan más dudas sobre el tema.

En ausencia de datos inequívocos sobre la eficacia de una técnica de cribado provinientes de estudios de intervención, los estudios de casos y controles se han mostrado útiles para esclarecer la eficacia de algunas técnicas (como en el caso del Papanicolaou). Los autores de este trabajo han elegido como variable de respuesta principal la mortalidad total que parece una variable importante, que evita algunos de los sesgos inherentes a los estudios de prevención (sesgo del adelanto diagnóstico) y permite salvar el problema del posible error en la causa de muerte en el certificado de defunción. Un estudio de casos y controles publicado recientemente y que utilizaba como variable principal la presencia de metástasis por cáncer de próstata sí que encontró una asociación entre el cribado y un menor riesgo.

En 2009 está prevista la publicación de dos estudios de intervención, uno americano y otro europeo, que es probable que despejen las dudas actuales sobre la conveniencia de llevar a cabo o no el cribado.

Bibliografía

  1. Nelson WG, De Marzo AM, Isaacs WB. Prostate cancer. N Engl J Med 2003; 349: 366-381. TC (s) PDF (s)
  2. Barry MJ. The PSA Conundrum. Arch Intern Med 2006; 166: 7-8. TC (s) PDF (s)

Autor

Manuel Iglesias Rodal. Correo electrónico: mrodal@menta.net.

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