Chap107N Prostate cancer Epidiomology and prevention

• (PCPT) Prostate Cancer Prevention Trial the 24.8% reduction of prostate cancer prevalence over a 7-year period in those men taking the 5alpha-reductase inhibitor, finasteride (Proscar 5mg per  day)
• REDUCE study using dutasteride (Avodart) (-23%)
• CombAT Trial (Avodart + Tamsulosin (Flomax) (-40% and no increase in high grade cancers)
• SELECT study using vitamin E and selenium (worse, Viy E increased prostate cancer by 17%)
• Physicians Health Study (PHSII) beta-carotene, Vit E, C or multivitamins (no benefit)

The PCPT tested the hypothesis that treatment with finasteride, which induces an acquired deficiency of type 2 5α-reductase, would lower intraprostatic DHT levels and thereby prevent prostate cancer.

In the PCPT, 18,882 men greater than or equal to 55 years of age with a normal digital rectal examination (DRE) and a prostate-specific antigen (PSA) level of less than or equal to 3.0 ng/mL were randomly assigned to treatment with finasteride (5 mg/day) or a placebo for 7 years.

4. Sexual side effects were more common with finasteride, whereas urinary symptoms were more common with the placebo.

1. The prevalence of prostate cancer was reduced by 24.8% (hazard ratio [HR] = 0.75, 95% CI = 18.6 to 30.6) from 24.4% to 18.4% in those participants randomized to finasteride compared with placebo.

2. The prevalence of Gleason grade 7 to 10 tumors was higher in the finasteride group than the placebo group (6.4% versus 5.1%, HR = 1.27, 95% CI = 1.07 to 1.50).

3. The risk reduction associated with finasteride among risk groups defined by age, family history, race, and PSA were of the same general magnitude.

4. Sexual side effects were more common with finasteride, whereas urinary symptoms were more common with the placebo.

A second large-scale trial of another 5ARI, dutasteride,completed accrual in the spring of 2005. This agentinhibits both type 1 and type 2 forms of 5α-reductase, isantiandrogenic, and promotes death of prostate cancercell lines (Lazier et al, 2004), and has been shown to reducethe risk of prostate cancer in men treated for lowerurinary tract symptoms related to benign prostaticenlargement when compared with the placebo (Andrioleet al, 2004c). The Eligibility for the Reduction by Dutasteride ofProstate Events (REDUCE) trial