The dilemma facing individuals wishing to make decisions regarding prostate cancer (PrCA) screening pivots on two opposing outcomes: over-diagnosing indolent cancer and under-diagnosing virulent cancer. In conjunction with limited data on which to draw conclusions, this dilemma formed the basis on which the US Preventive Services Task Force made its decision to not recommend PSA screening. Data driving that decision-making process was derived nearly entirely from European and European-American men, even though African Americans are much more likely to be diagnosed with later-stage, more aggressive disease at younger ages. The discrepancy that we see between the US' highest-world-quintile incidence rates and second-lowest-world-quintile mortality rates may be explained entirely by the presence of high-virulence disease among African Americans.

Clearly, detecting aggressive disease represents a significant public health issue and unmet clinical need. Development and discovery of biomarkers to predict PrCA that is likely to kill if left untreated is the major challenge in PrCA prevention and control. With this background in mind we sought to interrogate a large data set with multiple PSAs measured at regular (i.e., annual) intervals to see if we could predict high-virulence PrCA. Using the PLCO data we showed that with ≥three measures we were able to improve sensitivity and specificity of the PSA test to >97% overall and >99% among African-American men for detecting virulent, clinically relevant high-risk prostate cancer (PSA level ≥ 20ng/ml, cancer that invades prostate capsule, PrCA that involves more than one lobe, or Gleason score >7).

At this juncture, we have begun to address the question of what can be done to distinguish aggressive PrCA in African-American men. We propose creating a cohort of 48,000 individuals who are willing to undergo annual PSA screening with the intention of validating/refining the algorithm that the University of South Carolina team developed using PLCO trial data that combines three or more PSA measures to detect virulent, high-risk PrCA. This cohort also would serve another important purpose. There currently exists no other cohort with a sufficient number of African-American men to address other important cancer-related health issues. So, if designed correctly, this cohort could serve numerous other purposes.

This would be a simple follow-up study design with extensive baseline data collection and follow-up data collected at regular (i.e., annual) intervals. This would require strong community buy-in, commitment to providing information needed for informed decision-making, formulating rules for referring men out for diagnostic workup, and putting procedures in place for data linkage (e.g., to the cancer registries). Twelve institutions in 10 states across the US have expressed interest in being involved.

Currently, there are two, non-mutually exclusive, options for recruitment.

The Veterans Administration (VA) system could be ideal setting for this because: 1. They already have the screening infrastructure in place; 2. There isn't the financial incentive to over-diagnose and over-treat; 3. There is an excellent system of medical records; 4. There are many African-American veterans in the VA system; and 5. The medical home (for subsequent care) already is in place.

The NCI's community oncology research program (NCORP) appears to understand the CBPR imperative. As such, they have good access to local, interested communities and in some regions of the country this includes large AA populations. They have excellent community relations and local “connectivity” that could help to ensure a competent, caring ‘medical home' that would be essential for program viability (i.e., recruitment and follow-up). Depending on geographical particulars, there could be good overlap with the VA. NCORPS could add an important element of academic medicine/ NCI imprimatur to the mix.

Citation Format: James R. Hebert, Abraham Turner, Johnny Payne, Azza Shoaibi. Screening via multiple PSA measures to detect virulent prostate cancer could provide a way to address fundamental issues in African-American men's health. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C66.