Management of Low Risk and Low PSA Prostate Cancer: Long Term Results from the Prostate Cancer Intervention Versus Observation Trial

  • Timothy J. WiltEmail author
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 202)


Management of localized prostate cancer is controversial due in part to the lack of randomized controlled trial information in men diagnosed with prostate specific antigen (PSA) testing. Men with low risk or low PSA (<10 ng/ml) prostate cancer comprise up to 70 % of men currently diagnosed. Evidence suggests an excellent long-term prognosis with observation though nearly 90 % are treated with surgery (radical prostatectomy), external beam radiation, or brachytherapy. Results from the Prostate cancer Intervention Versus Observation Trial (PIVOT) provide high quality Level 1 evidence that observation compared to surgery results in similar long-term overall and prostate cancer survival, prevention of bone metastases and avoidance of surgery related harms. Combined with emerging evidence from screening, natural history, decision analysis and cost-effectiveness modeling studies, these data demonstrate that observation is the preferred treatment option for men with low risk and possibly low PSA prostate cancer. Recommending against PSA testing or, in men who still desire testing, raising thresholds of PSA values used to define abnormal, lengthening intervals between PSA tests and discontinuing testing in men with a life expectancy less than 15 years will reduce diagnostic and treatment related harms without adversely impacting overall or disease specific mortality and morbidity.


Prostate Cancer Bone Metastasis Prostate Specific Antigen Radical Prostatectomy Gleason Score 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Albertsen PC, Hanley JA, Barrows GH et al (2005) Prostate cancer and the Will Rogers phenomenon. J Natl Cancer Inst 97:1248–1253PubMedCrossRefGoogle Scholar
  2. Andriole G, Crawford ED, Grubb RL 3rd, Buys SS, Chia D, Church T et al (2012) PLCO project team. Prostate cancer screening in the randomized prostate, lung colorectal, ovarian cancer screening trial: mortality results after 13 years of follow-up. J Natl Cancer Inst 104:125–132Google Scholar
  3. Basch E, Oliver TK, Vickers A, Thompson I, Kantoff P, Parnes H et al (2012) Screening for prostate cancer with prostate-specific antigen testing: American society of clinical oncology provisional clinical opinion. J Clin Oncol 30:1–6CrossRefGoogle Scholar
  4. Bill-Axelson A, Holmberg L, Filen F et al (2008) Radical prostatectomy versus watchful waiting in localized prostate cancer: The Scandinavian prostate cancer group-4 randomized trial. J Natl Cancer Inst 100:1144–1154PubMedCrossRefGoogle Scholar
  5. Bill-Axelson A, Holmberg L, Ruutu M et al (2011) Radical prostatectomy versuswatchful waiting in localized prostate cancer: The Scandinavian prostate cancer group-4 randomized trial. N Engl J Med 264:1708–1717CrossRefGoogle Scholar
  6. Coen JJ, Feldman AS, Smith MR, Zietman AL (2011) Watchful waiting for localized prostate cancer in the PSA era: what have been the triggers for intervention? 107:1582–1586.22Google Scholar
  7. Cooperberg MR, Broering JM, Kantoff PW, Carroll PR (2007) Contemporary trends in low risk prostate cancer: risk assessment and treatment. J Urol 178(3 pt 2):S14–S19PubMedCentralPubMedCrossRefGoogle Scholar
  8. Cooperberg MR, Broering JM, Carroll PR (2010) Time trends and local variation in primary treatment of localized prostate cancer. J Clin Oncol 28:1117–1123PubMedCrossRefGoogle Scholar
  9. D’Amico AV, Whittington R, Malkowicz SB et al (1998) Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiationtherapy for clinically localized prostate cancer. JAMA 280:969–974PubMedCrossRefGoogle Scholar
  10. Daskivich TJ, Fan K-H, Koyama T, Albertsen PC, Goodman M, Hamilton AS et al (2013) Effect of age, Tumor risk, and comorbidity on competing risks for survival in a U.S. population–based cohort of men with prostate cancer. Ann Intern Med 158(10):709–717Google Scholar
  11. Djulbegovic M, Beyth RJ, Neuberger MM, Stoffs TL, Vieweg J, Djulbegovic B, Dahm P (2010) Screening for prostate cancer: systematic review and meta-analysis of randomised controlled trials. BMJ 341:c4543PubMedCentralPubMedCrossRefGoogle Scholar
  12. Donovan JL, Mills N, Smith, Brindle L, Jacoby A, Peters T et al (2002) Improving design and conduct of randomized trials by embedding them in qualitative research: ProtecT (prostate testing for cancer and treatment) study. BMJ 325:766–770Google Scholar
  13. Dubben H-H (2009) Trials of prostate cancer screening are not worthwhile. Lancet Oncol 10:294–9823PubMedCrossRefGoogle Scholar
  14. Eastham JA, Kattan MW, Riedel E, Begg CB, Wheeler TM, Gerigk C, Gonen M, Reuter V, Scardino PT (2003) Variations among individual surgeons in the rate of positive surgical margins in radical prostatectomy specimens. J Urol 170:2292–2295PubMedCrossRefGoogle Scholar
  15. Fleming C, Wasson JH, Albertsen PC, Barry MJ, Wennberg JE (1993) Prostate patient outcomes research team. A decision analysis of alternative treatment strategies for clinically localized prostate cancer. JAMA 269(20):2650–2658PubMedCrossRefGoogle Scholar
  16. Ganz PA, Barry JM, Burke W, Col NF, Corso PS, Dodson E et al (2012) National institutes of health state-of-the-science conference: role of active surveillance in the management of men with localized prostate cancer. Ann Intern Med 156(8):591–595Google Scholar
  17. Ghani KR, Grigor K, Tulloch DN, Bollina PR, McNeill SA (2005) Trends in reporting gleason score 1991 to 2001: Changes in the pathologist’s practice. Eur Urol 47:196–201PubMedCrossRefGoogle Scholar
  18. Gleason DF (1977) The Veteran’s administration cooperative urologic research group: histologic grading and clinical staging of prostatic carcinoma. In: Tannenbaum M (ed) Urologic pathology: the prostate. Lea and Febiger, Philadelphia, pp 171–198Google Scholar
  19. Graham J, Baker M, Macbeth F, Titshall V (2008) On behalf of the guideline development group. Diagnosis and treatment of prostate cancer: summary of NICE guidance. BMJ 336:610–612Google Scholar
  20. Gulati R, Gore JL, Etzioni R (2013) Comparative effectiveness of alternative prostate-specific antigen-based prostate cancer screening strategies: model estimates of potential benefits and harms. Ann Intern Med 158:145–153PubMedCentralPubMedCrossRefGoogle Scholar
  21. Hayes JH, Ollendorf DA, Pearson SD, Barry MJ, Kantoff PW, Lee P et al (2013) Observation versus Initial treatment for men with localized, low risk protate cancer. A cost-effectiveness analysis. Ann Intern Med 158:853–880PubMedCrossRefGoogle Scholar
  22. Iversen P, Madsen PO, Corle DK (1995) Radical prostatectomy versus expectanttreatment for early carcinoma of the prostate. Twenty-three yearfollow-up of a prospective randomized study. Scan J Urol Nephrol Suppl 172:65–72Google Scholar
  23. Klotz L, Zhang L, Lam A, Nam R, Mamedov A, Loblaw A (2010) Clinical results of long-term follow-up of a large active surveillance cohort with localized prostate cancer. J Clin Oncol 28:126–131PubMedCrossRefGoogle Scholar
  24. Lu-Yao GL, Albertsen PC, Moore DF, Shih W, Lin Y, DiPaola RS et al (2009) JAMA 302(11):1202–1209PubMedCentralPubMedCrossRefGoogle Scholar
  25. Moyer VA on behalf of the (2012) U.S. preventive services task force. screening for prostate cancer: U.S. preventive services task force recommendation statement. Ann Intern Med 157:120–134CrossRefGoogle Scholar
  26. Newschaffer CJ, Otani K, McDonald MK, Penberthy LT (2000) Causes of death in elderly prostate cancer patients and in a comparison nonprostate cancer cohort. J Natl Cancer Inst 92:613–621PubMedCrossRefGoogle Scholar
  27. Obek C, Sadek S, Lai S, Civantos F, Rubinowicz D, Soloway MS (1999) Positive surgical margins with radical retropubic prostatectomy: anatomic site-specific pathologic analysis and impact on prognosis. Urology 54:682–688PubMedCrossRefGoogle Scholar
  28. Ohori M, Wheeler TM, Kattan MW, Goto Y, Scardino PT (1995) Prognostic significance of positive surgical margins in radical prostatectomy specimens. J Urol 154:1818–1824PubMedCrossRefGoogle Scholar
  29. Qaseem A, Barry MJ, Denberg TD, Owens DK, Shekelle P (2013) For the clinical guidelines committee of the american college of physicians. Screening for prostate cancer: A guidance statement from the clinical guidelines committee of the American college of physicians. Ann Intern Med 158:761–769Google Scholar
  30. Rosario DJ, Lane JA, Metcalfe C, Donovan JL, Doble A et al (2012) Short term outcomes of prostate biopsy in men tested for cancer by prostate specific antigen: prospective evaluation within ProtecT study. BMJ 344:d7894PubMedCentralPubMedCrossRefGoogle Scholar
  31. Schellhammer P, Cockett A, Boccon-Gibod L et al (1997) Assessment of endpoints for clinical trials for localized prostate cancer. Urology 49:27–38PubMedCrossRefGoogle Scholar
  32. Schroder F, Hugosson J, Roobol M, Tammela T, Ciatto S, Nelen V et al (2012) Prostate-cancer mortality at 11 years of follow-up in a randomized European study. New Engl J Med 366:981–990PubMedCrossRefGoogle Scholar
  33. Shao Y-H, Demissie K, Shih W et al (2009) Contemporary risk profile of prostate cancer in the United States. J Natl Cancer Inst 101:1280–1283PubMedCrossRefGoogle Scholar
  34. Shteynshlyuger A, Andriole GL (2011) Cost-effectiveness of prostate specific antigen screening in the United States: extrapolating from the Eruopean study of screening for prostate cancer. J Urol 185:828–832PubMedCrossRefGoogle Scholar
  35. Stamey TA, Johnstone IM, McNeal JE, Lu AY, Yemoto CM (2002) Preoperative serum prostate specific antigen levels between 2 and 22 ng/mL correlate poorly with post-radical prostatectomy cancer morphology: prostate specific antigen cure rates appear constant between 2 and 9 ng/mL. J Urol 167:103–111PubMedCrossRefGoogle Scholar
  36. Swindle P, Eastham JA, Ohori M et al (2005) Do margins matter? The prognostic significance of positive surgical margins in radical prostatectomy specimens. J Urol 174:903–907PubMedCrossRefGoogle Scholar
  37. Thompson IM, Klotz L (2010) Active surveillance for prostate cancer. JAMA 204:2411–2412Google Scholar
  38. Vis AN, Schröder FH, van der Kwast TH (2006) The actual value of the surgical margin status as a predictor of disease progression in men with early prostate cancer. Eur Urol 50:258–265PubMedCrossRefGoogle Scholar
  39. Welch HG, Albertsen PC (2009) Prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening: 1986–2005. J Natl Cancer Inst 101:1325–1329PubMedCrossRefGoogle Scholar
  40. Welch HG, Black WC (2010) Overdiagnosis in cancer. J Natl Cancer Inst 102:605–613PubMedCrossRefGoogle Scholar
  41. Welch HG, Schwartz LM, Woloshin S (2005) Prostate-specific antigen levels in the United States: implications of various definitions for abnormal. J Natl Cancer Inst 97:1132–1137PubMedCrossRefGoogle Scholar
  42. Widmark A (2011) Prospective Randomized Trial Comparing External Beam Radiotherapy versus Watchful Waiting in Early Prostate Cancer. Abstract. Annual Meeting of the American Society of Radiation OncologyGoogle Scholar
  43. Wilt TJ, MacDonald R, Rutks I, Shamliyan TA, Taylor BC, Kane RL (2008a) Systematicreview: comparative effectiveness and harms of treatments for clinically localized prostate cancer. Ann Intern Med 148:435–448PubMedCrossRefGoogle Scholar
  44. Wilt TJ, Shamliyan T, Taylor B, MacDonald R, Tacklind J, Rutks I, Koeneman K, Cho C-S, Kane RL (2008) Comparative effectiveness of therapies for clinically localized prostate cancer. Comparative Effectiveness Review No 13. (Prepared by Minnesota Evidence-based Practice Center under Contract No. 290-02-00009.) Agency for Healthcare Research and Quality, Rockville, MD. Feb 2008Google Scholar
  45. Wilt TJ, Brawer MK, Barry MJ, Jones KM, Kwon Y, Gingrich JR, Aronson WJ, Nsouli I, Iyer P, Cartagena R, Snider G, Roehrborn C, Fox S (2009) 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 30:81–87PubMedCrossRefGoogle Scholar
  46. Wilt TJ, Brawer MB, Jones KM et al (2012) The prostate cancer intervention versus observation trial. N Engl J Med 367:203–213PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Minneapolis VA Center for Chronic Diseases Outcomes ResearchMinneapolisUSA

Personalised recommendations