Rationale: PSA screening detects too many low risk prostate cancers (PCas) and subjects too many men to prostate biopsy (PB). Hence, new diagnostic tests with improved specificity for aggressive PCa are needed. Prostate Health Index (PHI) measures 3 kallikrein isoforms and has been validated in multiple cohorts in Europe and the US for prediction of Gleason grade ?3+4 clinically significant (cs) PCa at PB. The test could prevent 30-58% of unnecessary PBs at a cost of deferring or missing detection of very few high-grade PCas.16- 18 Multi-parametric MRI of the prostate (MP-MRI) is similarly promising for detecting Gleason ?3+4 PCa.8,18,19 The PROMIS study from the UK resulted in a 27% reduction in unnecessary PBs with few missed cancers.19 However, both tests low specificity still subjects over half of men to unnecessary PB. Moreover, there is limited validation in Black men and almost no validation in Hispanics, thus precluding meaningful estimates of predictive accuracy in a high-risk and a growing population.18 Our long-term goal is to cost-effectively reduce PCa over-detection and unnecessary prostate biopsies. Brief Description:
Aim 1 is an observational study to identify effective thresholds of PHI and MRI used alone, in series (i.e. PHI +/- MP-MRI and MP-MRI+/-PHI) or in parallel (PHI & MRI) for detecting csPCa.
Aim 2 is a study to determine the most cost-effective strategy by race.
Aim 3 will assess the csPCas that were missed by MRI by careful pathologic review and highlighting the missed csPCa for corroboration on MP-MRI to see if they were truly not present on the MRI. All regions will be assigned a PIRADS Score. csPCas not seen on MRI will be characterized for Gleason grade, tumor size and extracapsular extension. We will also look for other aggressive features like comedonecrosis, cribriform histology, intraductal carcinoma, neuroendocrine differentiation, and lymphovascular and perineural invasion. We will address these objectives with the following Specific Aims: 1) Identify the biopsy strategies with highest specificity using PHI and MRI alone, in series, and in parallel to maximize the detection of clinically significant prostate cancer for biopsy-nave Black and Hispanic men; 2A) Compare the costs of the biopsy strategies for the detection of Gleason ?3+4 PCa at initial biopsy; 2B) Estimate the cost-effectiveness of each strategy relative to biopsying all men as the cost per Gleason ?3+4 PCa detected; 3) Characterize the MRI-blind lesions in Blacks and Hispanics men undergoing radical prostatectomy.
Recent studies highlight significant promise for multi-parametric MRI (MP-MRI) and Prostate Health Index (PHI) in biopsy-nave men to help ~25% of men avoid unnecessary prostate biopsies (PBs) while missing few clinically significant prostate cancers (csPCas). However, there is a need to increase the number of men who can safely avoid PB and expand it to Black and Hispanic men. Hence, we will 1) recruit Black and Hispanic biopsy-nave men with PSA from 4-10ng/ml into a comparative effectiveness study to identify strategies using PHI & MP-MRI alone, in series, and in parallel to develop race-specific biopsy strategies with PHI & MP-MRI, and 3) identify the most accurate and cost-effective biopsy strategy to detect csPCa and minimize unnecessary PBs.
