Improving Prostate Biopsy Efficiency: the Finasteride Challenge Test

Prostate cancer is the most common non-dermatologic neoplasm in men, affecting about one man in six in his lifetime. The primary public health approach for control of this disease is currently early diagnosis and treatment, relying primarily on the Prostate Specific Antigen (PSA) blood test for detection. Unfortunately, for most men with a PSA above 4.0 ng/mL (the most commonly-applied upper limit of normal), no prostate cancer is found at biopsy while many cancers are found below this 'normal' level. We have previously observed in the 18,882-person Prostate Cancer Prevention Trial (PCPT), a National Cancer Institute-sponsored study, that in men who received the drug finasteride, an inhibitor of the five alpha reductase type 2 enzyme and a medication used to improve urination, PSA was a better predictor of presence of prostate cancer. The most important predictor of the presence of prostate cancer was the change in PSA after beginning finasteride: men whose PSA did not change or increased had an almost 3-fold greater risk of having prostate cancer than those whose PSA decreased by 65% or more. Our hypothesis, based on these previous observations, is that PSA velocity during a 3-month treatment with finasteride more accurately predicts presence or absence of prostate cancer. To demonstrate the clinical usefulness of this test, we will recruit 500 men with an intermediate (20-60%) risk of prostate cancer and who are planning to undergo prostate biopsy to receive 3 months of finasteride at 5 mg/day. We plan to use our PCPT prostate cancer risk calculator to determine prostate cancer risk and subject eligibility. These men will be randomized in a 4:1 fashion to finasteride or placebo, will have PSA testing monthly and after 3 months will undergo prostate biopsy. We will then evaluate PSA velocity during these three months of finasteride treatment as a biomarker of prostate cancer on biopsy. We will then characterize the operating characteristics of PSA and digital rectal examination before and after finasteride treatment as well as determine the independent diagnostic value of the 3-month finasteride PSA velocity when added to the other prostate cancer risk factors used in the PCPT prostate cancer risk calculator. We will also compare the performance of PSA with finasteride treatment in combination or in place of the PCPT Risk Calculator to other newly developed prostate cancer biomarkers including PCA3, [-2]ProPSA, and TMPRSS2:ERG and evaluate the independent predictive value of these additional prostate cancer biomarkers on the performance of the PCPT Risk Calculator. The long term goal of this project is to develop a new methodology to improve prostate cancer detection while reducing the number of unnecessary prostate biopsies, procedures that are associated with considerable cost as well as potential for risks including infection and bleeding. PUBLIC HEALTH RELEVANCE: Hundreds of thousands of negative prostate biopsies occur each year in the US, most commonly prompted by an elevated PSA test. Finasteride, a drug used to treat prostate enlargement, appears to make PSA a more reliable test for cancer. We will determine if 3 months of treatment with finasteride will improve prostate cancer detection, with the potential for eliminating many of these unnecessary prostate biopsies.