BERKELEY, CA (UroToday.com) -
Should the low participation rate of young (<56 years) men with clinically insignificant prostate cancer in active surveillance be increased?
Prostate-specific antigen (PSA) screening, hailed as a means of detecting prostate cancer early has, since its adoption, led to a spike in incidence rates [1] with the greatest increase (7-fold) evident in the group <50 years of age. Some investigators also have recently questioned whether screening leads to unnecessary treatment for a subset of cases.[2] Equally important, with widespread PSA screening, the last 20 years have witnessed stage migration of the disease with nearly 50% of cases now defined as low-risk (Gleason score <7, PSA <10 ng/ml, and cT1c/T2a).[3]Within the low-risk group, “clinically insignificant” tumors [4]) are a subset with an even more favorable prognosis (PSA density 0.1 ng/ml/g prostate gland, Gleason <7, maximum of two involved cores, and <50 % tumor in the involved core(s)). Evidence that some of these cancers are treated unnecessarily is supported by the observation that for patients with untreated low-risk[5] prostate cancer, the probability of dying from a cause unrelated to this malignancy in the decade after diagnosis is about 19 times that of suc-cumbing to their disease.[6]
Over-treatment is the subject of vigorous debate due to (a) fertility loss, incontinence, and erectile dysfunction, side effects more likely to impact a physically or sexually active younger cohort, and (b) treatment costs. An alternative to immediate therapy is active surveillance, a management approach in which cases of low-risk disease are regularly tested for disease progression and only those beieved to be at risk for progression are treated. However, some investigators question the appropriateness of active surveillance for young men for two reasons: (a) life expectancy is long, and (b) current diagnostic parameters for identifying clinically insignificant cases are imperfect. A counter-argument to the first point is that young men may be candidates if more stringent surveillance entrance criteria are employed (e.g. those defining clinically insignificant disease).[7]
We recently reported[8] that of all prostate cancer cases diagnosed in U.S. Air Force (USAF) per-sonnel, 62 % were low-risk. Surprisingly, of these, >90 % of the men opted for definitive therapy, despite their youth (average age, 48 years) and the potential for side effects. Certainly, immediate treatment would likely be the most appropriate course of action for some of these low-risk cases. However, the subset of low-risk cases that are clinically insignificant might be an appropriate group for active surveillance programs. Our ongoing research is aimed at identifying such individuals.
At civilian hospitals, active surveillance is being considered with increased frequency[9] in order to delay or minimize the impact of treatment side effects. Many factors influence decision-making for low-risk prostate cancer, including patient anxiety and physician recommendations,[10] though we do not know which of these drives the high rate of definitive treatment for the cohort of USAF servicemen with PSA-detected, low-risk disease. Such studies have been initiated and could lead to the implementation of psychosocial interventions to enhance the decision-making process.
Current preoperative parameters for identifying PSA-detected tumors that will remain asymptomatic are inexact. What is needed is either a biomarker(s) or a genetic classifier which, in conjunction with current clinicopathologic parameters, increases the accuracy in identifying cases that will remain indolent. Our planned studies will interrogate (using molecular inversion probe technology) the genome of DNA from tumors towards building a multivariate predictor of clinically insignificant disease.
The potential for overtreatment of clinically insignificant prostate cancer in young men (<56 years) has significant consequences, including adverse side effects and treatment costs. Knowing what factors lead to choosing definitive intervention, as well as identifying a genetic classifier that (ultimately combined with diagnostic parameters) could identify tumors that pose no threat, could lead to a higher participation in active surveillance for this age cohort. In turn, treatment would be focused on those individuals most likely to benefit, which would reduce health costs[11]) while sparing those least likely to benefit the adverse side effects associated with therapy.
References:
- Welch HG, Albertsen PC. Prostate cancer diagnosis and treatment after the introduction of pros-tate-specific antigen screening: 1986-2005. J Natl Cancer Inst 2009;101.
- Draisma G, Etzioni R, Tsodikov A, Mariotto A, Wever E, Gulati R, Feuer E, de Koning H. Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and con-text. J Natl Cancer Inst 2009;101:374-383374.
- Moul JW, Mouraviev V, Sun L, Schroeck FR, Polascik TJ. Prostate cancer: the new landscape. Current Opinion in Urology 2009;19:154-160.
- Epstein JI, Walsh PC, Carmichael M, Brendler CB. Pathologic and clinical findings to predict tumor extent of nonpalpable (Stage T1c) prostate cancer. JAMA 1994;271:368.
- O'Donnel H, Parker C. What is low-risk prostate cancer and its natural history. World Journal of Urology 2008;26:415-422.
- Albertsen PC. Treatment of localized prostate cancer: when is active surveillance appropriate. Nature Reviews Clinical Oncology 2010;7:394-400.
- Klotz LH. Active Surveillance for prostate cancer: A Review. Current Urology Reports 2010;11:165-171.
- Del Junco DJ, Fox EE, Cooper S, Goldhagen M, Koda E, Rogers D, Canby-Hagino E, Kim J, Pettaway C, Boyd DD. Increasing rates of low-risk prostate cancer incidence in USAF service-men and selection of treatments. J Urology 2011;185:2137-2142.
- Hosemann S. Organ-confined prostate cancer. Oncolog 2009;54:4-6.
- Zeliadt SB, Ramsey SD, Penson DF, Ekwueme DU, Stroud L, Lee JW. Why do men choose one treatment over another? A review of patient decision making for localized prostate cancer. Cancer 2011;106:1865-1874.
- Corcoran AT, Peele PB, Benoit RM. Cost comparison between watchful waiting with active surveillance and active treatment of clinically localized prostate cancer. Urology 2010;76:703-709.
Written by:
Jeri Kim, MD, Patricia Parker, PhD, and Douglas Boyd, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
UroToday.com Prostate Cancer Section