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Prostate cancer screening: current status and future perspectives

Nature Reviews Urology volume 7, pages 487–493 (2010)Cite this article

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Abstract

With the publication of the long-term results of two randomized screening trials and updates to screening guidelines from many organizations, the past 2 years have been eventful in the field of prostate cancer screening. Both the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial—which failed to identify a benefit of screening in a community setting—and the European Randomized Study of Screening for Prostate Cancer—which showed a modest benefit to screening in a clinical trial setting—have sought to address the role of screening in reducing mortality from prostate cancer. Epidemiologic evidence supports the role of PSA screening in the stage and grade migration of prostate cancer, but to date the evidence for its role in changing mortality patterns is more equivocal. As a result, little support exists at present among urologic and cancer prevention organizations for population-based PSA screening. Particularly in the USA, where PSA screening has been relatively widespread, reductions in prostate-cancer-specific mortality are likely to be in part related to improvements in treatment, rather than solely to PSA screening. The substantial risk of overdiagnosis and overtreatment of latent prostate cancer means that methods to increase the specificity of prostate cancer screening, and particularly its ability to identify high-risk disease, are essential. Strategies such as the use of 5α-reductase inhibitors in high-risk patients, and the continued development of urinary and genetic markers hold promise in this regard.

Key Points

  • Epidemiologic evidence both supports and questions the effectiveness of PSA screening in reducing prostate cancer mortality

  • Overall, evidence supports the role of PSA screening in the observed stage and grade migration of prostate cancer

  • Little support exists among urologic and cancer prevention organizations for population-based PSA screening

  • Randomized trials (ERSPC and PLCO) have not resolved the controversies regarding PSA screening

  • Strategies to improve the performance of PSA testing and to better define aggressive disease are needed

  • Such strategies include the ongoing development of urinary markers, use of 5α-reductase inhibitors, and continued exploration of markers of aggressive disease

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References

  1. Jemal, A. et al. Cancer statistics, 2009. CA Cancer J. Clin. 59, 225–249 (2009).

    PubMed  Google Scholar 

  2. Holmberg, L. et al. A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N. Engl. J. Med. 347, 781–789 (2002).

    Article  PubMed  Google Scholar 

  3. Farkas, A., Schneider, D., Perrotti, M., Cummings, K. B. & Ward, W. S. National trends in the epidemiology of prostate cancer, 1973 to 1994: evidence for the effectiveness of prostate-specific antigen screening. Urology 52, 444–448 (1998).

    Article  CAS  PubMed  Google Scholar 

  4. Welch, H. G. & Albertsen, P. C. Prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening: 1986–2005. J. Natl Cancer Inst. 101, 1325–1329 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kvale, R. et al. Interpreting trends in prostate cancer incidence and mortality in the five Nordic countries. J. Natl Cancer Inst. 99, 1881–1887 (2007).

    Article  PubMed  Google Scholar 

  6. Shao, Y. H. et al. Contemporary risk profile of prostate cancer in the United States. J. Natl Cancer Inst. 101, 1280–1283 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Moore, A. L. et al. Population-based prostate-specific antigen testing in the UK leads to a stage migration of prostate cancer. BJU Int. 104, 1592–1598 (2009).

    Article  PubMed  Google Scholar 

  8. Kopec, J. A. et al. Screening with prostate specific antigen and metastatic prostate cancer risk: a population based case–control study. J. Urol. 174, 495–499 (2005).

    Article  PubMed  Google Scholar 

  9. Etzioni, R., Gulati, R., Falcon, S. & Penson, D. F. Impact of PSA screening on the incidence of advanced stage prostate cancer in the United States: a surveillance modeling approach. Med. Decis. Making 28, 323–331 (2008).

    Article  PubMed  Google Scholar 

  10. Draisma, G. 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. 95, 868–878 (2003).

    Article  PubMed  Google Scholar 

  11. Kondylis, F. I., Moriarty, R. P., Bostwick, D. & Schellhammer, P. F. Prostate cancer grade assignment: the effect of chronological, interpretive and translation bias. J. Urol. 170, 1189–1193 (2003).

    Article  PubMed  Google Scholar 

  12. Albertsen, P. C. et al. Prostate cancer and the Will Rogers phenomenon. J. Natl Cancer Inst. 97, 1248–1253 (2005).

    Article  PubMed  Google Scholar 

  13. Wolters, T. et al. The effect of study arm on prostate cancer treatment in the large screening trial ERSPC. Int. J. Cancer 126, 2387–2393 (2010).

    CAS  PubMed  Google Scholar 

  14. Horner, M. J. et al. Table 23.1: cancer of the prostate (invasive). Surveillance Epidemiology and End Results [online], (2009).

    Google Scholar 

  15. Collin, S. M. et al. Prostate-cancer mortality in the USA and UK in 1975–2004: an ecological study. Lancet Oncol. 9, 445–452 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Agalliu, I., Weiss, N. S., Lin, D. W. & Stanford, J. L. Prostate cancer mortality in relation to screening by prostate-specific antigen testing and digital rectal examination: a population-based study in middle-aged men. Cancer Causes Control 18, 931–937 (2007).

    Article  PubMed  Google Scholar 

  17. Bartsch, G. et al. Prostate cancer mortality after introduction of prostate-specific antigen mass screening in the Federal State of Tyrol, Austria. Urology 58, 417–424 (2001).

    Article  CAS  PubMed  Google Scholar 

  18. Bartsch, G. et al. Tyrol Prostate Cancer Demonstration Project: early detection, treatment, outcome, incidence and mortality. BJU Int. 101, 809–816 (2008).

    Article  CAS  PubMed  Google Scholar 

  19. Etzioni, R. et al. Quantifying the role of PSA screening in the US prostate cancer mortality decline. Cancer Causes Control 19, 175–181 (2008).

    Article  PubMed  Google Scholar 

  20. Etzioni, R. & Feuer, E. Studies of prostate-cancer mortality: caution advised. Lancet Oncol. 9, 407–409 (2008).

    Article  PubMed  Google Scholar 

  21. Concato, J. et al. The effectiveness of screening for prostate cancer: a nested case–control study. Arch. Intern. Med. 166, 38–43 (2006).

    Article  PubMed  Google Scholar 

  22. Shibata, A., Ma, J. & Whittemore, A. S. Prostate cancer incidence and mortality in the United States and the United Kingdom. J. Natl Cancer Inst. 90, 1230–1231 (1998).

    Article  CAS  PubMed  Google Scholar 

  23. Oliver, S. E., Gunnell, D. & Donovan, J. L. Comparison of trends in prostate-cancer mortality in England and Wales and the USA. Lancet 355, 1788–1789 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Shaw, P. A. et al. An ecologic study of prostate-specific antigen screening and prostate cancer mortality in nine geographic areas of the United States. Am. J. Epidemiol. 160, 1059–1069 (2004).

    Article  PubMed  Google Scholar 

  25. Lu-Yao, G. et al. Natural experiment examining impact of aggressive screening and treatment on prostate cancer mortality in two fixed cohorts from Seattle area and Connecticut. BMJ 325, 740 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Barry, M. J. The PSA conundrum. Arch. Intern. Med. 166, 7–8 (2006).

    Article  PubMed  Google Scholar 

  27. Albertsen, P. C., Hanley, J. A. & Fine, J. 20-year outcomes following conservative management of clinically localized prostate cancer. JAMA 293, 2095–2101 (2005).

    Article  CAS  PubMed  Google Scholar 

  28. Carroll, P. et al. Prostate-specific antigen best practice statement: 2009 update. American Urological Association [online], (2009).

    Google Scholar 

  29. Abrahamsson, P. A., Artibani, W., Chapple, C. R. & Wirth, M. European Association of Urology position statement on screening for prostate cancer. Eur. Urol. 56, 270–271 (2009).

    Article  PubMed  Google Scholar 

  30. Ito, K., Kakehi, Y., Naito, S. & Okuyama, A. Japanese Urological Association guidelines on prostate-specific antigen-based screening for prostate cancer and the ongoing cluster cohort study in Japan. Int. J. Urol. 15, 763–768 (2008).

    Article  PubMed  Google Scholar 

  31. Smith, R. A., Cokkinides, V., Brooks, D., Saslow, D. & Brawley, O. W. Cancer screening in the United States, 2010: a review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J. Clin. 60, 99–119 (2010).

    Article  PubMed  Google Scholar 

  32. Lim, L. S. & Sherin, K. Screening for prostate cancer in U. S. men: ACPM position statement on preventive practice. Am. J. Prev. Med. 34, 164–170 (2008).

    Article  PubMed  Google Scholar 

  33. National Health Service. Prostate Cancer Risk Management Programme [online], (2010).

  34. Lin, K., Lipsitz, R., Miller, T. & Janakiraman, S. 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. 149, 192–199 (2008).

    Article  PubMed  Google Scholar 

  35. Prorok, P. C. et al. Design of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Control. Clin. Trials 21 (6 Suppl.), 273S–309S (2000).

    Article  CAS  PubMed  Google Scholar 

  36. Grubb, R. L. III et al. Prostate cancer screening in the Prostate, Lung, Colorectal and Ovarian cancer screening trial: update on findings from the initial four rounds of screening in a randomized trial. BJU Int. 102, 1524–1530 (2008).

    Article  PubMed  Google Scholar 

  37. Pinsky, P. F. et al. Prostate biopsy following a positive screen in the prostate, lung, colorectal and ovarian cancer screening trial. J. Urol. 173, 746–750 (2005).

    Article  PubMed  Google Scholar 

  38. Andriole, G. L. et al. Mortality results from a randomized prostate-cancer screening trial. N. Engl. J. Med. 360, 1310–1319 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Schröder, F. H. et al. Screening and prostate-cancer mortality in a randomized European study. N. Engl. J. Med. 360, 1320–1328 (2009).

    Article  PubMed  Google Scholar 

  40. Roobol, M. J., Grenabo, A., Schröder, F. H. & Hugosson, J. Interval cancers in prostate cancer screening: comparing 2- and 4-year screening intervals in the European Randomized Study of Screening for Prostate Cancer, Gothenburg and Rotterdam. J. Natl Cancer Inst. 99, 1296–1303 (2007).

    Article  PubMed  Google Scholar 

  41. Albertsen, P. C. Efficacy vs effectiveness in prostate-specific antigen screening. J. Natl Cancer Inst. 102, 288–289 (2010).

    Article  CAS  PubMed  Google Scholar 

  42. Wever, E. M. et al. Prostate-specific antigen screening in the United States vs in the European Randomized Study of Screening for Prostate Cancer-Rotterdam. J. Natl Cancer Inst. 102, 352–355 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Bill-Axelson, A. et al. Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial. J. Natl Cancer Inst. 100, 1144–1154 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Widmark, A. et al. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet 373, 301–308 (2009).

    Article  CAS  PubMed  Google Scholar 

  45. Stephenson, A. J. et al. Prostate cancer-specific mortality after radical prostatectomy for patients treated in the prostate-specific antigen era. J. Clin. Oncol. 27, 4300–4305 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Thompson, I. M. et al. Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower. JAMA 294, 66–70 (2005).

    Article  CAS  PubMed  Google Scholar 

  47. Thompson, I. M. et al. The influence of finasteride on the development of prostate cancer. N. Engl. J. Med. 349, 215–224 (2003).

    Article  CAS  PubMed  Google Scholar 

  48. Thompson, I. M. et al. Effect of finasteride on the sensitivity of PSA for detecting prostate cancer. J. Natl Cancer Inst. 98, 1128–1133 (2006).

    Article  CAS  PubMed  Google Scholar 

  49. Andriole, G. L. et al. Effect of dutasteride on the risk of prostate cancer. N. Engl. J. Med. 362, 1192–1202 (2010).

    Article  CAS  PubMed  Google Scholar 

  50. Andriole, G. et al. The effect of dutasteride on the utility of PSA for the diagnosis of high-grade and clinically relevant prostate cancer in men with a previous negative biopsy: results from the REDUCE study. J. Urol. (in press).

  51. Ploussard, G. & de la Taille, A. Urine biomarkers in prostate cancer. Nat. Rev. Urol. 7, 101–109 (2010).

    Article  CAS  PubMed  Google Scholar 

  52. Wang, R., Chinnaiyan, A. M., Dunn, R. L., Wojno, K. J. & Wei, J. T. Rational approach to implementation of prostate cancer antigen 3 into clinical care. Cancer 115, 3879–3886 (2009).

    Article  CAS  PubMed  Google Scholar 

  53. Zheng, S. L. et al. Cumulative association of five genetic variants with prostate cancer. N. Engl. J. Med. 358, 910–919 (2008).

    Article  CAS  PubMed  Google Scholar 

  54. Gelmann, E. P. Complexities of prostate-cancer risk. N. Engl. J. Med. 358, 961–963 (2008).

    Article  CAS  PubMed  Google Scholar 

  55. Lilja, H. et al. Long-term prediction of prostate cancer up to 25 years before diagnosis of prostate cancer using prostate kallikreins measured at age 44 to 50 years. J. Clin. Oncol. 25, 431–436 (2007).

    Article  CAS  PubMed  Google Scholar 

  56. Loeb, S. et al. Baseline prostate-specific antigen compared with median prostate-specific antigen for age group as predictor of prostate cancer risk in men younger than 60 years old. Urology 67, 316–320 (2006).

    Article  PubMed  Google Scholar 

  57. Ulmert, D. et al. Prostate-specific antigen at or before age 50 as a predictor of advanced prostate cancer diagnosed up to 25 years later: a case–control study. BMC Med. 6, 6 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Fang, J. et al. Low levels of prostate-specific antigen predict long-term risk of prostate cancer: results from the Baltimore Longitudinal Study of Aging. Urology 58, 411–416 (2001).

    Article  CAS  PubMed  Google Scholar 

  59. Draisma, G. et al. Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. J. Natl Cancer Inst. 101, 374–383 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Washington University School of Medicine, Barnes–Jewish Hospital, Siteman Cancer Center, 4960 Children's Place, Campus Box 8242, St Louis, 63110, MO, USA

    Seth A. Strope & Gerald L. Andriole

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Contributions

S. A. Strope and G. L. Andriole researched data for the article and made substantial contributions to discussion of content. S. A. Strope was involved in writing the article. S. A. Strope and G. L. Andriole took part in review/editing of the manuscript before submission.

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Correspondence to Gerald L. Andriole.

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Competing interests

G. L. Andriole declares that he has acted as a consultant for Gen-Probe, GlaxoSmithKline and Onconome, and has received speakers bureau honoraria from GlaxoSmithKline. S. A. Strope declares no competing interests.

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Strope, S., Andriole, G. Prostate cancer screening: current status and future perspectives. Nat Rev Urol 7, 487–493 (2010). https://doi.org/10.1038/nrurol.2010.120

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