Annals of Long Term Care

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Clinical Trial: PCPT . The Prostate Cancer Prevention Trial (PCPT) was published in a July 2003 issue of the New England Journal of Medicine.⁷ Currently, no medical therapies are effective for the prevention of prostate cancer. The purpose of this study was to determine whether long-term treatment with the 5-a-reductase inhibitor finasteride could reduce the prevalence of prostate cancer in healthy men. The study enrolled 18,882 men 55 years of age or older (38% >=65 years of age) with a normal digital rectal exam, a prostatespecific antigen (PSA) concentration less than 3.0 ng/mL, and an American Urological Association (AUA) symptom score less than 20. Subjects were randomized to double-blind therapy with placebo or finasteride 5 mg once daily. The study was stopped 15 months early by the data and safety monitoring committee based on evidence that the study objective had been met. After a follow-up of 7 years, the primary outcome evaluated was prevalence of prostate cancer by prostate biopsy. Results were published for the 86.3% of men who had completed 7 years of the study; however, approximately 25% of the men in the study refused an end-of-study prostate biopsy. Thus, the overall number included in the final analyses was 9060. At study termination, finasteride significantly reduced the prevalence of prostate cancer by 25% compared to placebo. In the finasteride group, 18.4% of men were diagnosed with cancer compared with 24.4% in the placebo group (RRR, 24.8%; 95% CI, 18.6-30.6%; P<0.001). However, 6.4% of those in the finasteride group were diagnosed with high-grade cancer (Gleason score 7-10) compared to only 5.1% in the placebo group (relative risk, 1.27; 95% CI, 1.07-1.50; P = 0.005). Hence, the NNT to prevent one case of prostate cancer with finasteride was 17 patients, while the number needed to harm one patient with high-grade cancer was 77 patients. Adverse effects also differed between groups: those in the finasteride group had significantly more erectile dysfunction, loss of libido, gynecomastia, and reduced ejaculate volume compared to those in the placebo group, who had significantly more urinary urgency, urinary frequency, urinary retention, urinary tract infections, and prostatitis (P<0.001 for all comparisons).

PCPT Conclusions and Clinical Impact. Seven years of finasteride 5 mg per day significantly reduced prostate cancer but at the cost of increased high-grade cancer and sexual side effects. Application of this data in clinical practice will need to be on a patient-specific basis after a provider–patient discussion of risks and benefits of therapy.

Clinical Trial: MTOPS. The Medical Therapy Of Prostatic Symptoms (MTOPS) study was published in a December 2003 issue of the New England Journal of Medicine.⁸ Prior to this study, short-term combined drug therapy was not shown to be superior to single-drug therapy in reducing urinary symptoms of benign prostatic hyperplasia (BPH). Thus, the purpose of this study was to evaluate whether long-term therapy with an alpha-blocker, a 5-a-reductase inhibitor, or the combination would delay or prevent clinical progression of BPH. The double-blind study enrolled 3047 men age 50 years and older (mean age, 63 years) with BPH and an AUA symptom score of 8-30. At baseline, the mean AUA score was 17 out of 35 total points and the mean prostate volume was 36 mL. Subjects were randomized to one of four treatment arms: placebo, doxazosin 1 mg titrated up to 4-8 mg at bedtime, finasteride 5 mg at bedtime, or the combination of doxazosin and finasteride. After a mean follow-up period of 4.5 years, the primary outcome evaluated was overall clinical progression of BPH, defined as a first occurrence of an increase of four points in AUA score over baseline, acute urinary retention, renal insufficiency, recurrent urinary tract infection, or UI.