Journal Review

BACKGROUND Androgens are involved in the development of prostate cancer. Finasteride, an inhibitor of 5alpha-reductase, inhibits the conversion of testosterone to dihydrotestosterone, the primary androgen in the prostate, and may reduce the risk of prostate cancer. METHODS In the Prostate Cancer Prevention Trial, we randomly assigned 18,882 men 55 years of age or older with a normal digital rectal examination and a prostate-specific antigen (PSA) level of 3.0 ng per milliliter or lower to treatment with finasteride (5 mg per day) or placebo for seven years. Prostate biopsy was recommended if the annual PSA level, adjusted for the effect of finasteride, exceeded 4.0 ng per milliliter or if the digital rectal examination was abnormal. It was anticipated that 60 percent of participants would have prostate cancer diagnosed during the study or would undergo biopsy at the end of the study. The primary end point was the prevalence of prostate cancer during the seven years of the study. RESULTS Prostate cancer was detected in 803 of the 4368 men in the finasteride group who had data for the final analysis (18.4 percent) and 1147 of the 4692 men in the placebo group who had such data (24.4 percent), for a 24.8 percent reduction in prevalence over the seven-year period (95 percent confidence interval, 18.6 to 30.6 percent; P<0.001). Tumors of Gleason grade 7, 8, 9, or 10 were more common in the finasteride group (280 of 757 tumors [37.0 percent], or 6.4 percent of the 4368 men included in the final analysis) than in the placebo group (237 of 1068 tumors [22.2 percent], P<0.001 for the comparison between groups; or 5.1 percent of the 4692 men included in the final analysis, P=0.005 for the comparison between groups). Sexual side effects were more common in finasteride-treated men, whereas urinary symptoms were more common in men receiving placebo. CONCLUSIONS Finasteride prevents or delays the appearance of prostate cancer, but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer.

[1]  Eter,et al.  THE EFFECT OF FINASTERIDE ON THE RISK OF ACUTE URINARY RETENTION AND THE NEED FOR SURGICAL TREATMENT AMONG MEN WITH BENIGN PROSTATIC HYPERPLASIA , 2000 .

[2]  J. Crowley,et al.  Design of the Prostate Cancer Prevention Trial (PCPT). , 1995, Controlled clinical trials.

[3]  M. Pike,et al.  5-alpha-reductase activity and risk of prostate cancer among Japanese and US white and black males , 1992, The Lancet.

[4]  M M Elhilali,et al.  Outcome of sextant biopsy according to gland volume. , 1997, Urology.

[5]  Bostwick Dg.  Prostatic adenocarcinoma following androgen deprivation therapy: the new difficulty in histologic interpretation. , 1998 .

[6]  Stephanie Green,et al.  Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria , 1992, Investigational New Drugs.

[7]  S B Malkowicz,et al.  Biochemical Outcome After Radical Prostatectomy , External Beam Radiation Therapy , or Interstitial Radiation Therapy for Clinically Localized Prostate Cancer , 2000 .

[8]  J. Reichardt,et al.  Hormones and prostate cancer: Current perspectives and future directions , 2002, The Prostate.

[9]  P. Walsh.  Influence of prostate volume in the detection of prostate cancer. , 2003, The Journal of urology.

[10]  D. Bostwick.  Prostatic adenocarcinoma following androgen deprivation therapy: the new difficulty in histologic interpretation. , 1998, Anatomic pathology.

[11]  P. Walsh.  Treatment with finasteride preserves usefulness of prostate-specific antigen in the detection of prostate cancer: results of a randomized, double-blind, placebo-controlled clinical trial. , 1999, The Journal of urology.

[12]  R. Prehn.  On the prevention and therapy of prostate cancer by androgen administration. , 1999, Cancer Research.

[13]  M. Soloway,et al.  Histopathological effects of androgen deprivation in prostatic cancer. , 1996, Seminars in urologic oncology.

[14]  H A Feldman,et al.  Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. , 1994, The Journal of urology.

[15]  Michael W Kattan,et al.  Cancer control with radical prostatectomy alone in 1,000 consecutive patients. , 2002, The Journal of urology.

[16]  W. Murphy,et al.  Histologic changes in prostate carcinomas treated with leuprolide (luteinizing hormone–‐releasing hormone effect). Distinction from poor tumor differentiation , 1994, Cancer.

[17]  M. Barry,et al.  The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. , 1992, The Journal of urology.

[18]  M. Sporn,et al.  Treatment and prevention of intraepithelial neoplasia: an important target for accelerated new agent development. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[19]  J. Crowley,et al.  Biomarker-based methods for determining noncompliance in a prevention trial. , 2002, Controlled clinical trials.

[20]  Ximing J. Yang,et al.  Does long-term finasteride therapy affect the histologic features of benign prostatic tissue and prostate cancer on needle biopsy? , 1999 .

[21]  S. Lippman,et al.  Cancer prevention science and practice. , 2002, Cancer research.

[22]  J. Hanley,et al.  Competing risk analysis of men aged 55 to 74 years at diagnosis managed conservatively for clinically localized prostate cancer. , 1999, JAMA.

[23]  S. Lippman,et al.  Cancer prevention by delay. Commentary re: J. A. O'Shaughnessy et al., Treatment and Prevention of Intraepithelial Neoplasia: An Important Target for Accelerated New Agent Development. Clin. Cancer Res., 8: 314-346, 2002. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[24]  P. Kantoff,et al.  The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Ricky A. Sharma,et al.  Cancer prevention and delay are as important as cure. , 2003, The Lancet. Oncology.

[26]  P. Humphrey,et al.  Prostate-specific antigen cutoff of 2.6 ng/mL for prostate cancer screening is associated with favorable pathologic tumor features. , 2002, Urology.

[27]  S. Ishikawa,et al.  Prognostic factors in survival free of progression after androgen deprivation therapy for treatment of prostate cancer. , 1989, The Journal of urology.

[28]  M. Marberger,et al.  Associations of serum testosterone with microvessel density, androgen receptor density and androgen receptor gene polymorphism in prostate cancer. , 2003, The Journal of urology.