AUA 2017: Racial Disparities and Genetic Variabilities in Prostate Cancer

Boston, MA (UroToday.com) In this session, Dr. Kim reviewed the epidemiology, clinical framework, complexity and shortcomings of the present clinical data in active surveillance for prostate cancer. Additionally, he provided an outstanding overview of the potential molecular mechanisms of racial disparities in prostate cancer outcomes, and how those findings have the potential for influencing treatment paradigms.

Dr. Kim demonstrated that in 2009-2013, non-Hispanic African Americans had a 1.73 times increased risk of diagnosis, 2.29 times higher rate of death overall and a 1.32 times higher rate of death after disease diagnosis. Active surveillance is a recommended treatment for very low risk and low risk prostate cancers. However, there has been no consensus on enrollment criteria or monitoring, and most active surveillance cohorts have a disproportionately small component of African-American men. Therefore, Dr. Kim wondered if urologists could safely apply current surveillance criteria and programs to African-American men.

A study from Johns Hopkins and Rutgers Universities used both UCSF and NCCN active surveillance criteria to evaluate men who chose radical prostatectomy who were eligible for active surveillance. Of patients treated at their centers, it was determined that a higher proportion of African American men were upstaged at radical prostatectomy (>pT3) then their white counterparts (19.4% vs 10.1%, p=0.037). Additionally, a literature review showed wide disagreement amongst single and multi-institutional, and administrative database cohort analyses published studies since 2009.

Newest data from a multi-institutional study examined pathologic findings of 1,923 whites and 333 African American men who were eligible for active surveillance. In their pooled outcomes, no differences were demonstrated in the rates of upstaging, Gleason grade, upgrading, path weight, or positive surgical margin. When sub-analyzed by institution, there were wide discrepancies in upstaging rates of African Americans, ranging from 10.80 to 0 times increased risk.

Several molecular mechanisms have been proposed which may be the impetus of these findings. This includes the androgen/androgen receptor, growth factor/receptor and apoptosis. In the androgen pathway, the 5 alpha reductase gene, CYP17, CYP34A, and androgen receptor gene have all been implicated in mechanisms of oncologic aggressiveness. IGF-1, IGFB-3, EGFR, EphB2, BCL-2, MDM2 all have been identified in growth factor or apoptotic pathways that may influence treatment resistance as well.

RNA sequencing has preliminarily demonstrated clustering by race, and trends can be demonstrated by population. However, no obvious pathway defect is present, as four pathways have been shown to be up-regulated in African Americans while over ten pathways have been down-regulated. Additionally, TCGA sequencing has shown no association between exome sequence and race.

In summary, significant clinical disparities have been demonstrated between races in patients with prostate cancer. Molecular mechanisms of resistance have been proposed, however institutional biases may influence treatment outcomes. Present data does not support altering active surveillance enrollment criteria or monitoring due to race. Future prospective studies are needed to help decipher this challenging topic.

Presented By: Isaac Y. Kim, MD, PhD, MBA

Written By: David B. Cahn, DO, MBS, Fox Chase Cancer Center
Twitter: @dbcahn

at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA
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