Current Treatment Options in Oncology

, Volume 7, Issue 5, pp 355–362

Active surveillance versus radical treatment for favorable-risk localized prostate cancer

  • Laurence Klotz

Opinion statement

Widespread prostate-specific antigen (PSA) screening in North America has resulted in a profound stage migration and a marked increase in incidence. One in six men is now diagnosed, many with small-volume, low-grade cancer. This incidence is dramatically higher than the 3% lifetime risk of prostate cancer death that characterized the prescreening era. This article summarizes the case for active surveillance for “favorable-risk” prostate cancer with selective delayed intervention for rapid biochemical progression, assessed by increasing PSA levels, or grade progression. The results of a large phase II trial using this approach are reviewed. To date, this study has shown that virtually all men with favorable-risk prostate cancer managed in this fashion will die of unrelated causes. Based on the Swedish randomized trial of radical prostatectomy versus watchful waiting, the Connecticut observation series, and the Toronto active surveillance experience, a number needed to treat analysis of the benefit of radical treatment of all newly diagnosed favorable-risk prostate cancer patients, compared with a strategy of active surveillance with selective delayed intervention, is presented. This suggests that approximately 73 patients will require radical treatment for each prostate cancer death averted. This translates into a 3- to 4-week survival benefit, unadjusted for quality of life. This figure is confirmed based on an analysis of the 2004 D'Amico et al. PSA velocity data in favorable-risk disease. The approach of active surveillance with selective delayed intervention based on PSA doubling time and repeat biopsy represents a practical compromise between radical therapy for all patients (which results in overtreatment for patients with indolent disease) and watchful waiting with palliative therapy only (which results in undertreatment for those with aggressive disease).


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References and Recommended Reading

  1. 1.
    Sakr WA, Haas GP, Cassin BF, et al.: The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients. J Urol 1993, 150:379–385. This study demonstrated the high prevalence of histologic prostate cancer in men in their 20s and 30s dying of unrelated causes, mostly trauma, and suggests that the lead time from inception of disease to clinical diagnosis is approximately 30 years.PubMedGoogle Scholar
  2. 2.
    Boring CC, Squires TS, Tong T: Cancer statistics, 1993. CA Cancer J Clin 1993, 43:7–26.PubMedCrossRefGoogle Scholar
  3. 3.
    Jemal A, Tiwari RC, Murray T, et al.: Cancer statistics, 2004. CA Cancer J Clin 2004, 54:8–29.PubMedCrossRefGoogle Scholar
  4. 4.
    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, 97:1132–1137.PubMedCrossRefGoogle Scholar
  5. 5.
    Thompson IM, Goodman PJ, Tangen CM, et al.: The influence of finasteride on the development of prostate cancer. N Engl J Med 2003, 349:215–224 This landmark trial was the first to subject a large cohort of men with a normal PSA to prostate biopsy; it showed a 25% positive biopsy rate in the placebo arm, confirming the serious risks of overdiagnosis of clinically insignificant disease. It also showed a 25% reduction in the risk of diagnosing prostate cancer in men treated with finasteride for 7 years.PubMedCrossRefGoogle Scholar
  6. 6.
    McGregor M, Hanley JA, Boivin JF, et al.: Screening for prostate cancer: estimating the magnitude of overdetection. CMAJ 1998, 159:1368.PubMedGoogle Scholar
  7. 7.
    Etzioni R, Penson DF, Legler JM, et al.: Overdiagnosis due to prostate-specific antigen screening: lessons from U.S. prostate cancer incidence trends. J Natl Cancer Inst 2002, 94:981–990.PubMedGoogle Scholar
  8. 8.
    Pound CR, Partin AW, Eisenberger MA, et al.: Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999, 281:1591–1597. This important study of 2000 radical prostatectomies at Johns Hopkins University reported that the median time from surgery to prostate cancer death was 16 years in patients failing radical prostatectomy.PubMedCrossRefGoogle Scholar
  9. 9.
    Tornblom M: Lead time associated with screening for prostate cancer. Int J Cancer 2004, 108:122–129.PubMedCrossRefGoogle Scholar
  10. 10.
    Albertsen PC, Hanley JA, Fine J: 20-Year outcomes following conservative management of clinically localized prostate cancer. JAMA 2005, 293:2095–2101. This population-based study of watchful waiting in Connecticut showed that men with Gleason 6 or less prostate cancer had a risk of prostate cancer mortality at 20 years of between 15% and 23% without treatment. For most of these men, the risk of a non-prostate cancer death was much higher.PubMedCrossRefGoogle Scholar
  11. 11.
    Stamey TA, Freiha FS, McNeal JE, et al.: Localized prostate cancer. Relationship of tumor volume to clinical significance for treatment of prostate cancer. Cancer 1993, 71:933–938.PubMedCrossRefGoogle Scholar
  12. 12.
    Epstein JI, Walsh PC, Carmichael M, et al.: Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA 1994, 271:368–374.PubMedCrossRefGoogle Scholar
  13. 13.
    Epstein JI, Pizov G, Walsh PC: Correlation of pathologic findings with progression after radical retropubic prostatectomy. Cancer 1993, 71:3582–3593.PubMedCrossRefGoogle Scholar
  14. 14.
    Epstein JI, Carmichael M, Partin AW, et al.: Is tumor volume an independent predictor of progression following radical prostatectomy? A multivariate analysis of 185 clinical stage B adenocarcinomas of the prostate with 5 years of followup. J Urol 1993, 149:1478–1481.PubMedGoogle Scholar
  15. 15.
    Epstein JI, Chan DW, Sokoll LJ, et al.: Nonpalpable stage T1c prostate cancer: prediction of insignificant disease using free/total prostate specific antigen levels and needle biopsy findings. J Urol 1998, 160:2407–2411.PubMedCrossRefGoogle Scholar
  16. 16.
    Goto Y, Ohori M, Arakawa A, et al.: Distinguishing clinically important from unimportant prostate cancers before treatment: value of systematic biopsies. J Urol 1996, 156:1059–1063.PubMedCrossRefGoogle Scholar
  17. 17.
    Kattan MW, Eastham JA, Wheeler TM, et al.: Counseling men with prostate cancer: a nomogram for predicting the presence of small, moderately differentiated, confined tumors. J Urol 2003, 170:1792–1797.PubMedCrossRefGoogle Scholar
  18. 18.
    Augustin H, Hammerer PG, Graefen M, et al.: Insignificant prostate cancer in radical prostatectomy specimen: time trends and preoperative prediction. Eur Urol 2003, 43:455–460.PubMedCrossRefGoogle Scholar
  19. 19.
    Noguchi M, Stamey TA, McNeal JE, et al.: Relationship between systematic biopsies and histological features of 222 radical prostatectomy specimens: lack of prediction of tumor significance for men with nonpalpable prostate cancer. J Urol 2001, 166:104–109; discussion 109-110.PubMedCrossRefGoogle Scholar
  20. 20.
    Irwin MB, Trapasso JG: Identification of insignificant prostate cancers: analysis of preoperative parameters. Urology 1994, 44:862–867; discussion 867-868.PubMedCrossRefGoogle Scholar
  21. 21.
    Cupp MR, Bostwick DG, Myers RP, Oesterling JE: The volume of prostate cancer in the biopsy specimen cannot reliably predict the quantity of cancer in the radical prostatectomy specimen on an individual basis. J Urol 1995, 153:1543–1548.PubMedCrossRefGoogle Scholar
  22. 22.
    Anast JW, Andriole GL, Bismar TA, et al.: Relating biopsy and clinical variables to radical prostatectomy findings: can insignificant and advanced prostate cancer be predicted in a screening population. Urology 2004, 64:544–550.PubMedCrossRefGoogle Scholar
  23. 23.
    Choo R, DeBoer G, Klotz L, et al.: PSA doubling time of prostate carcinoma managed with watchful observation alone. Int J Radiat Oncol Biol Phys 2001, 50:615–620.PubMedCrossRefGoogle Scholar
  24. 24.
    Kakehi Y: PSA DT in Japanese active surveillance cohort (48 patients). Jpn J Clin Oncol 2003, 33:1–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Egawa S, Arai Y, Tobisu K, et al.: Use of pretreatment prostate-specific antigen doubling time to predict outcome after radical prostatectomy. Prostate Cancer Prostatic Dis 2000, 3:269–274.PubMedCrossRefGoogle Scholar
  26. 26.
    McLaren DB, McKenzie M, Duncan G, et al.: Watchful waiting or watchful progression?: Prostate specific antigen doubling times and clinical behavior in patients with early untreated prostate carcinoma. Cancer 1998, 82:342–348.PubMedCrossRefGoogle Scholar
  27. 27.
    D'Amico AV, Chen MH, Roehl KA, Catalona WJ: Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N Engl J Med 2004, 351:125–135. This study demonstrated that a PSA increase of more than 2 in the year before surgery identified 100% of men destined to die of prostate cancer (despite surgery) over the next 10 years.PubMedCrossRefGoogle Scholar
  28. 28.
    Choo R, Klotz L, Danjoux C, et al.: Feasibility study: watchful waiting for localized low to intermediate grade prostate carcinoma with selective delayed intervention based on prostate specific antigen, histological and/or clinical progression. J Urol 2002, 167:1664–1669. This was the first report of a large cohort managed with the strategy of active surveillance with selective delayed intervention based on PSA kinetics and/or grade progression.PubMedCrossRefGoogle Scholar
  29. 29.
    Klotz L: Active surveillance for prostate cancer: for whom. J Clin Oncol 2005, 23:8165–8169.PubMedCrossRefGoogle Scholar
  30. 30.
    Klotz L: Active surveillance for good risk prostate cancer: rationale, method, and results. Can J Urol 2005, 12:21–24.PubMedGoogle Scholar
  31. 31.
    Bill-Axelson A, Holmberg L, Ruutu M, et al.: Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2005, 352:1977–1984. This critical study reports the updated results of a unique randomized trial of surgery versus watchful waiting, showing a 44% reduction in prostate cancer mortality at 10 years with radical prostatectomy.PubMedCrossRefGoogle Scholar
  32. 32.
    Steineck G, Helgesen F, Adolfsson J, et al.: Quality of life after radical prostatectomy or watchful waiting. N Engl J Med 2002, 347:790–796. This is a companion study to the Scandinavian randomized study of watchful waiting versus prostatectomy, showing no difference in any domain related to psychological functioning, depression, or general sense of well being in patients managed expectantly. This suggests that the psychological stress of untreated and treated cancer is similar.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2006

Authors and Affiliations

  • Laurence Klotz
    • 1
  1. 1.Sunnybrook Health Sciences CenterUniversity of TorontoTorontoCanada

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