Category: screening

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]
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Routine HIV Screening – HIV: CDC x USPSTF


Após acabar de publicar as recomendações do US Preventive Services Task Force sobre ECG (não triar), acabo de ler o ahead of print do New England Journal of Medicine que discute justamente as recomendações da Task Force (não triar universalmente HIV) contra as recomendações do Centers for Disease Control (triagem universal).

O artigo faz um apanhado interessante da discussão entre as duas entidades acerca da análise das mesmas evidências científicas, destacando que, a despeito das evidências não serem as mesmas, a análise de diferentes pesquisadores (cochranistas x especialistas).

Os dois grupos debatem sob diversas óticas, incluindo a da economia da saúde (de custo-benefício e custo-efetividade), a do risco relacionado a triagem e da responsabilidade das próprias entidades em se obrigarem a fazer ou não recomendações.

As referências são bastante interessantes, e a ótica do autor deste artigo traduz a panacéia que existe em torno da Medicina Baseada em Evidências.

Lembrando que só recentemente o atual presidente Barack Obama suspendeu a obrigatoriedade do exame de HIV para imigrantes, uma exigência da administração anterior, é importante entender o contexto em que se desenvolvem estas recomendações.

Leia o artigo do NEJM:




Publicado originalmente por Leonardo C M Savassi
.
Publicado originalmente no Blog Medicina de Família
http://medicinadefamiliabr.blogspot.com

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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
    CrossRef | Web of Science | Medline

  5. 5
    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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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.

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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.

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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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