**3.1 Prostate Cancer Prevention Trial (PCPT)**

The Prostate Cancer Prevention Trial was the first large multicenter randomized double blind prostate prevention trial using a 5-ARI. In 2003, 18,882 men, 55 years or older with a PSA level less than 3.0ng/mL and a normal digital rectal exam (DRE) were randomized for seven years to finasteride 5mg daily or placebo.

Of the men who participated, 48%, or 9060 men were included in the final analysis. Enrollment criteria included men 55 years or older who were free of prostate cancer, no other significant co morbidities, and an American Urological Association symptom score (AUA-SS) of less than 20. Eligible participants were required to have a PSA less than 3.0ng/ml, normal DRE, adherent to the study protocol and no side effects during placebo. Men were contacted every three months for medical event evaluation and were seen by the

clinical trials suggest a benefit.22 A small clinical trial (n=60) using oral green tea catechins (GTC) found that patients with HGPIN randomized to GTC vs. placebo had no change in PSA levels, but did have less progression of prostate cancer: 1 patient vs. 9 patients

Soy, like green tea, was also found to demonstrate lower prostate cancer in epidemiologic studies between diets high in soy versus western diets. The benefit is potentially a 70% reduction of prostate cancer.24 Soy affects signaling pathways, specifically Wnt and Hh

DIM (the dimeric product of indole-3-carbinol) is found in a variety of plants and has been shown to inhibit alpha reductase suggesting that it may have an inhibitory role in prostate cancer. Curcumin is a bioavailable agent in turmeric and is also an alpha reductase inhibitor. Other regulators along the tumor pathway are inhibited by these two substances. Clinical

Currently no biologically available micronutrients have been proven to provide chemoprevention benefits of prostate cancer. As such, current patient recommendations are

We reviewed the multicenter randomized double blind studies focused on 5-ARI usage versus placebo for prostate cancer chemoprevention including the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events

The Prostate Cancer Prevention Trial was the first large multicenter randomized double blind prostate prevention trial using a 5-ARI. In 2003, 18,882 men, 55 years or older with a PSA level less than 3.0ng/mL and a normal digital rectal exam (DRE) were randomized for

Of the men who participated, 48%, or 9060 men were included in the final analysis. Enrollment criteria included men 55 years or older who were free of prostate cancer, no other significant co morbidities, and an American Urological Association symptom score (AUA-SS) of less than 20. Eligible participants were required to have a PSA less than 3.0ng/ml, normal DRE, adherent to the study protocol and no side effects during placebo. Men were contacted every three months for medical event evaluation and were seen by the

PSA <3.0 ng/mL DRE Normal

PSA 2.5-10 ng/mL DRE Normal

Trial Population Risk Category Agent Target Reported

Finasteride

Dutasteride

(Merck) Type 1 5-ARI 2008

(GlaxoSmithKline) Type 1,2 5-ARI 2009

signaling. Randomized studies are currently being performed.

to eat healthy foods and pursue healthy lifestyle changes.25

**3. Review of 5-ARI chemoprevention trials** 

(REDUCE). Table 1 compares their study design.

Table 1. Comparison of PCPT & REDUCE trials.

**3.1 Prostate Cancer Prevention Trial (PCPT)** 

seven years to finasteride 5mg daily or placebo.

trials are required to evaluate their effects.

progress.23

Prostate Cancer

Dutasteride of Prostate Cancer Events Trial

Reduction by

Prevention Trial (PCPT) n = 18,882

(REDUCE) n = 8,229

study site every six months for side effect evaluation and medication refills. Annual PSA and DRE were performed. Biopsy was recommended if the DRE was abnormal or PSA was greater than 4.0ng/ml in the placebo arm or 2.0 times PSA (adjusted to 2.3x in year 4) in the finasteride arm. At the completion of the trial in year seven, all participants were recommended to undergo an end of study prostate biopsy with at least six cores. All biopsies were reviewed by a blinded pathologist.

The primary endpoint of the study was the prevalence of prostate cancer as diagnosed by biopsy for cause or end of study biopsies. Prostate cancer was found in 24.4% of the placebo group (1,147/4,692) and 18.4% of the finasteride group (803/4,368), representing a 24.8% risk reduction (CI 19-31, p<0.001). Finasteride's relative benefit was found across all groups including age, race/ethnicity, family history and entry PSA. In addition, Finasteride also reduced the risk of HGPIN compared to placebo.

Interestingly, tumors with a Gleason grade of 7-10, high grade tumors, were found to be more prevalent in the finasteride group (37%), 280 of 757 graded tumors, as compared to the placebo group (22%), 237 of 1,068 graded tumors. This was statistically significant (P<.001). The increased prevalence of high grade tumors in the treatment group has generated tremendous speculation and sub-analysis. Forty of the excess high grade tumors were found in the "for cause" biopsies, clinically indicated due to increasing PSA or changes in the DRE.

Secondary analyses have found a detection bias demonstrating a net reduction in highgrade cancers and a 53% reduction in low grade cancers.26 However, due disagreement in the medical community regarding finasteride's effect on high-grade cancers, it was not given a new indication for prostate cancer prevention.
