R E V I E W Role of 5 alpha-reductase inhibitors in the management of prostate cancer Steven J Hudak1 Javier Hernandez1 Ian M Thompson2 1Urology Service, Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, TX, USA; 2Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA Correspondence: Javier Hernandez Urology Service, Department of Surgery, Brooke Army Medical Center, 3851 Roger Brooke Drive, Fort Sam Houston, TX 78234-6200, Tel +1 210 916 1163 Fax +1 210 916 5076 Email javier.hernandez@us.army.mil Note: The views expressed in this article are those of the authors and do not reﬂect the ofﬁcial policy of the Department of Defense or other Departments of the US Government. Abstract: Prostate cancer is one of the most complex and enigmatic oncologic problems in medicine. It is highly prevalent, particularly in elderly males. Unfortunately, its generally protracted and variable clinical course and high association with treatment-related morbidity raise serious questions about the ideal treatment strategy for the individual patient. 5 alpha- reductase (5AR) inhibitors have a dramatic effect on benign prostatic disease with low toxicity. Thus, there is much interest in the potential role of 5AR inhibitors in the prevention and treatment of prostate cancer. Finasteride is the only agent that has been shown in a randomized clinical trial to decrease the risk of prostate cancer with a reduction of almost 25%. Additionally, a recent analysis of the Prostate Cancer Prevention Trial (PCPT) has found that ﬁnasteride improves the performance characteristics of prostate-speciﬁc antigen (PSA) blood test as a screening tool for prostate cancer, for both cancer detection as well as for detection of high risk disease. Finally, 5AR inhibitors have been studied as a component of multimodal therapy for all stages of prostate cancer, with the goal of improving oncologic outcomes while avoiding the toxicity of medical and surgical castration. Keywords: prostate cancer, 5-α-reductase inhibitors, ﬁnasteride, dutasteride, chemoprevention Introduction Prostate cancer is the most common noncutaneous malignancy in males. The American Cancer Society estimates that in the year 2006, a total of 234 460 men will be diagnosed with prostate cancer and 27 350 will die of this disease (Jemal et al 2006). At the start of the year 2003, nearly 2 million American men were living with prostate cancer. Most commonly a disease of elderly men, the average age at diagnosis is 68 and 27.3% of all new diagnoses are in men 75 years of age or older (Ries et al 2006). The characteristics of prostate cancer have changed dramatically since the introduction of prostate-specific antigen (PSA)-based screening in 1986. PSA screening has led to a drastic increase in the detection rate of prostate cancer along with an associated downward stage migration. While there are no prospective, randomized studies that prove earlier detection of prostate cancer leads to decreased mortality, the reality is that widespread PSA-based screening for prostate cancer has continued. Taking into consideration that many tumors currently detected may be of an indolent nature, a current challenge is identifying the patient who may benefit from treatment for whom side effects of treatment may be acceptable. The high prevalence and considerably lower mortality of prostate cancer, coupled with the signiﬁcant potential morbidity of therapy for prostate cancer, have sparked much interest in alternative approaches against prostate cancer such as prevention (Thompson et al 2003), minimally invasive surgical therapies (Ahmed et al 2005; Tooher et al 2006) and active surveillance strategies (Carter et al 2002). Well designed randomized clinical trials addressing questions in these areas will hopefully lead to more efﬁcacious and appropriate treatment of prostate cancer with lower disease speciﬁc mortality, while minimizing treatment related morbidity. Medical therapy Clinical Interventions in Aging 2006:1(4) 425–431 © 2006 Dove Medical Press Limited. All rights reserved 425