Current Urology Reports

, 18:80 | Cite as

Active Surveillance for Intermediate Risk Prostate Cancer

Prostate Cancer (S Prasad, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Prostate Cancer

Abstract

Purpose of Review

Active surveillance is now widely utilized for the management of low-risk prostate cancer (PCa). The limits of surveillance for men with intermediate risk cancer are controversial. While there is a broad consensus that men with low-risk disease can be safely managed with AS, many potential candidates, including those with Gleason 3 + 4 disease, PSA >10, younger men and African-Americans are often excluded.

Recent Findings

Outcome data for intermediate-risk patients managed by active surveillance demonstrate reasonable outcomes, but these men clearly are at higher risk for progression to metastatic disease. The use of biomarkers and multiparametric MRI will enable a more precise and personalized risk assessment. Literature describing the effects of young age on outcomes is limited, but the experience reported in prospective series with 15–20 year follow-up suggests it is a safe approach. African-American men are at greater risk for occult co-existent higher-grade disease, but in the absence of this their outcome is favorable.

Summary

Patients with intermediate-risk PCa should not be excluded from active surveillance based on a single criterion. Treatment decisions should be based on multiple parameters, including percent Gleason 4, PSA density, cancer volume on biopsy, MRI findings, and patient age and co-morbidity. Genetic tissue-based biomarkers are also likely to play a role in enhancing decision making.

Keywords

Prostate cancer Active surveillance Intermediate risk 

Notes

Compliance with Ethical Standards

Conflict of Interest

Laurence Klotz declares no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    • Choo R, Klotz L, Danjoux C, Morton GC, DeBoeer G, Szumacher E, 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(4):1664–9. The first paper reporting the outcome of ‘active surveillance’. CrossRefPubMedGoogle Scholar
  2. 2.
    Zlotta AR, Egawa S, Pushkar D, et al. Prevalence of prostate cancer on autopsy: cross-sectional study on unscreened Caucasian and Asian men. J Natl Can Inst. 2013;105(14):1050–8.CrossRefGoogle Scholar
  3. 3.
    Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012;367(3):203.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Bill-Axelson A, Holmberg L, Garmo H, et al. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med. 2014;370(10):932.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    •• Hamdy FC, Donovan JL, Lane JA, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. 2016;375(15):1415. The pivotal PROTECT study which successfully randomized more than 1600 patients between surgery, radiation, and ‘active monitoring’. No difference in 10 year PCSM, but worse progression rate in the active monitoring group (which included 23% intermediate-high risk patients). CrossRefPubMedGoogle Scholar
  6. 6.
    •• Klotz L, Vesprini D, Sethukavalan P, Jethava V, Zhang L, Jain S, et al. Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. J Clin Oncol. 2015;33(3):272–7. This important study reported the long term results of an ‘inclusive’ approach to surveillance, emphasizing both the long term safety and increased risk in intermediate risk cancer. CrossRefPubMedGoogle Scholar
  7. 7.
    Bul M, Zhu X, Valdagni R, Pickles T, Kakehi Y, Rannikko A, et al. Active surveillance for low-risk prostate cancer worldwide: the PRIAS study. Eur Urol. 2013;63(4):597–603.CrossRefPubMedGoogle Scholar
  8. 8.
    •• Tosoian JJ, Mamawala M, Epstein JI, Landis P, Wolf S, Trock BJ, et al. Intermediate and longer-term outcomes from a prospective active-surveillance program for favorable-risk prostate cancer. J Clin Oncol. 2015;33(30):3379–85. Long term results of a restrictive approach to surveillance, with a PCSM < 1%. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Selvadurai ED, Singhera M, Thomas K, Mohammed K, Woode-Amissah R, Horwich A, et al. Parker CC medium-term outcomes of active surveillance for localised prostate cancer. Eur Urol. 2013;64(6):981–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Welty CJ, Cowan JE, Nguyen H, Shinohara K, Perez N, Greene KL, et al. Extended followup and risk factors for disease reclassification in a large active surveillance cohort for localized prostate cancer. J Urol. 2015;193(3):807–11.CrossRefPubMedGoogle Scholar
  11. 11.
    • Musunuru HB, Yamamoto T, Klotz L, Ghanem G, Mamedov A, Sethukavalan P, et al. Active surveillance for intermediate risk prostate cancer: survival outcomes in the Sunnybrook experience. J Urol. 2016;196(6):1651–8. This study, and reference 12 below, stratify men in the Toronto cohort according to the risk of metastasis, and identify the presence of Gleason pattern 4 at baseline, but not PSA > 10, as a significant predictor for metastatic disease despite close surveillance. CrossRefPubMedGoogle Scholar
  12. 12.
    Yamamoto T, Musunuru B, Vesprini D, Zhang L, Ghanem G, Loblaw A, et al. Metastatic prostate cancer in men initially treated with active surveillance. J Urol. 2016;195(5):1409–14.CrossRefPubMedGoogle Scholar
  13. 13.
    Klotz L, Emberton M. Management of low risk prostate cancer-active surveillance and focal therapy. Nat Rev Clin Oncol. 2014;11(6):324–34.CrossRefPubMedGoogle Scholar
  14. 14.
    Stattin P, Holmberg E, Johansson JE, et al. Outcomes in localized prostate cancer: National Prostate Cancer Register of Sweden follow-up study. J Natl Cancer Inst. 2010;102:950–8.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Cooperberg MR, Cowan JE, Hilton JF, et al. Outcomes of active surveillance for men with intermediate-risk prostate cancer. J Clin Oncol. 2011;29:228–34.CrossRefPubMedGoogle Scholar
  16. 16.
    Lu-Yao GL, Albertsen PC, Moore DF, et al. Outcomes of localized prostate cancer following conservative management. JAMA. 2009;302:1202–9.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Newcomb LF, Thompson IM Jr, Boyer HD, et al. Outcomes of active surveillance for clinically localized prostate cancer in the prospective, multi-institutional canary PASS cohort. J Urol. 2016;195:313–20.CrossRefPubMedGoogle Scholar
  18. 18.
    Morash C, Tey R, Agbassi C, et al. Active surveillance for the management of localized prostate cancer: Guideline recommendations. Can Urol Assoc J. 2015;9(5–6):171–8.Google Scholar
  19. 19.
    Chen RC, Rumble RB, Loblaw DA, Finelli A, Ehdaie B, Cooperberg MR, et al. Active surveillance for the Management of Localized Prostate Cancer (Cancer Care Ontario Guideline): American Society of Clinical Oncology clinical practice guideline endorsement. J Clin Oncol. 2016;34(18):2182–90.CrossRefPubMedGoogle Scholar
  20. 20.
    NICE. National Collaborating Centre for Cancer. Prostate Cancer: Diagnosis and Treatment. Clinical Guideline. http: http://www.nice.org.uk.myaccess.library.utoronto.ca/nicemedia/live/14348/66232/66232.pdf.
  21. 21.
    Schiavina R, Borghesi M, Brunocilla E, et al. The biopsy Gleason score 3+4 in a single core does not necessarily reflect an unfavourable pathological disease after radical prostatectomy in comparison with biopsy Gleason score 3+3: looking for larger selection criteria for active surveillance candidates. Prostate Cancer Prostatic Dis. 2015;18:270–5.CrossRefPubMedGoogle Scholar
  22. 22.
    Gandaglia G, Ploussard G, Isbarn H, et al. What is the optimal definition of misclassification in patients with very low-risk prostate cancer eligible for active surveillance? Results multiinstitutional series. Urol Oncol. 2015;33:164.CrossRefPubMedGoogle Scholar
  23. 23.
    Huang CC, Kong MX, Zhou M, et al. Gleason score 3+4=7 prostate cancer with minimal quantity of gleason pattern 4 on needle biopsy is associated with low-risk tumor in radical prostatectomy specimen. Am J Surg Pathol. 2014;38:1096–101.PubMedGoogle Scholar
  24. 24.
    Hong SK, Vertosick E, Sjoberg DD, et al. Insignificant disease among men with intermediate-risk prostate cancer. World J Urol. 2014;32:1417–21.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Cole AI, Morgan TM, Spratt DE, et al. Prognostic value of percentage Gleason grade 4 at prostate biopsy in predicting prostatectomy pathology and recurrence. J Urol. 2016;196:405–11.CrossRefPubMedGoogle Scholar
  26. 26.
    Welty CJ, Cowan JE, Nguyen H, et al. Extended followup and risk factors for disease reclassification in a large active surveillance cohort for localized prostate cancer. J Urol. 2015;193:807–11.CrossRefPubMedGoogle Scholar
  27. 27.
    •• Sakr WA, Grignon DJ, Crissman JD, Heilbrun LK, Cassin BJ, Pontes JJ, et al. High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20-69: an autopsy study of 249 cases. In Vivo. 1994;8(3):439–43. A classic autopsy study showing a high rate of autopsy identified prostate cancer beginning in the 30s. PubMedGoogle Scholar
  28. 28.
    •• Inoue LY, Trock BJ, Partin AW, Carter HB, Etzioni R. Modeling grade progression in an active surveillance study. Stat Med. 2014;33(6):930–9. The best estimate of spontaneous grade progression over time from Gleason pattern 3 to 4 of 1-2% per year. CrossRefPubMedGoogle Scholar
  29. 29.
    • Leapman MS, Cowan JE, Nguyen HG, et al. Active surveillance in younger men with prostate cancer. J Clin Oncol. 2017;35(17):1898–1904. An important study showing the safety of surveillance in young men. Google Scholar
  30. 30.
    Sundi D, Ross AE, Humphreys EB, et al. African American men with very lowrisk prostate cancer exhibit adverse oncologic outcomes after radical prostatectomy: should active surveillance still be an option for them? J Clin Oncol. 2013;31:2991–7.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Sundi D, Faisal FA, Trock BJ, et al. Reclassification rates are higher among African American men than Caucasians on active surveillance. Urology. 2015;85:155–60. 55CrossRefPubMedGoogle Scholar
  32. 32.
    Jalloh M, Myers F, Cowan JE, et al. Racial variation in prostate cancer upgrading and upstaging among men with low-risk clinical characteristics. Eur Urol. 2015;67:451–7.CrossRefPubMedGoogle Scholar
  33. 33.
    Leapman MS, Freedland SJ, Aronson WJ, et al. Pathological and biochemical outcomes among African-American and Caucasian men with low risk prostate cancer in the SEARCH database: implications for active surveillance candidacy. J Urol. 2016;196:1408–14.CrossRefPubMedGoogle Scholar
  34. 34.
    Klein EA, Haddad Z, Yousefi K, Lam LL, Wang Q, Choeurng V, et al. Decipher genomic classifier measured on prostate biopsy predicts metastasis risk. Urology. 2016;90:148–52.CrossRefPubMedGoogle Scholar
  35. 35.
    Nguyen PL, Martin NE, Choeurng V, Palmer-Aronsten B, Kolisnik T, Beard CJ, et al. Utilization of biopsy-based genomic classifier to predict distant metastasis after definitive radiation and short-course ADT for intermediate and high-risk prostate cancer. Prostate Cancer Prostatic Dis. 2017; doi: 10.1038/pcan.2016.58.
  36. 36.
    Cullen J, Rosner IL, Brand TC, et al. A biopsy-based 17-gene genomic prostate score predicts recurrence after radical prostatectomy and adverse surgical pathology in a racially diverse population of men with clinically low- and intermediate-risk prostate cancer. Eur Urol. 2015;68:123.CrossRefPubMedGoogle Scholar
  37. 37.
    Brand TC, Zhang N, Crager MR, et al. Patient-specific meta-analysis of 2 clinical validation studies to predict pathologic outcomes in prostate cancer using the 17-gene genomic prostate score. Urology. 2016;89:69.CrossRefPubMedGoogle Scholar
  38. 38.
    Cuzick J, Berney DM, Fisher G, et al. Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br J Cancer. 2012;106:1095.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    • Cuzick J, Stone S, Fisher G, et al. Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort. Br J Cancer. 2015;113:382. One of the only biomarker studies with a PCSM end point. Strong validation of the Prolaris assay CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Division of Urology, Sunnybrook Health Sciences CentreUniversity of TorontoTorontoCanada

Personalised recommendations