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AUA 2020

AUA 2020: Detection Of Germline Mutations in Localized and Metastatic Prostate Cancer Through Guideline-Based Testing

(UroToday.com) Historically, it has been felt that there is a relative paucity of important germline mutations in patients with prostate cancer. However, recent work has identified important rates of mutations, particularly in DNA damage repair (DDR) pathways. The initial work in this space focused on men with advanced disease. However, more recent work has looked at this earlier in the disease process. In a podium presentation at the American Urologic Association (AUA) 2020 Virtual Annual Meeting, Randy Vince, MD, and colleagues presented an analysis examining rates of germline mutations in men with both metastatic and localized disease undergoing testing for clinical, rather than research, based indications.


The authors utilized a single institutional cohort of men diagnosed with prostate cancer at Michigan Medicine and Michigan Institute of Urology (MIU) between 2017 and 2019. These men were offered multi-gene panel testing in accordance with NCCN BRCA-Related Breast and/or Ovarian Cancer Syndrome (HBOC) guidelines. Patient data was tracked in a prospectively collected registry, and rates of pathogenic/likely pathogenic mutations and variants of uncertain significance (VUS) were compared according to patient demographic and disease characteristics.


Over the three years of the study interval, 299 patients underwent testing, including 150 men with metastatic PCa and 149 with localized prostate cancer (PCa). Median age was 69 (39-98) and the vast majority (92%) were Caucasian. 

Interestingly, rates of pathogenic/likely pathogenic germline mutations were lower in patients with metastatic disease (5.3%) than those with localized disease (11.4%). 
localized_vs_metastatic_disease.png

The most common mutations were in CHEK2 (44%), ATM (12%) and BRCA2 (12%), and FANCA (8%).
GeneticMutations.png

The authors conclude that a meaningful proportion of men with both localized and metastatic prostate cancer have potentially actionable mutations, particularly in key DDR genes.

Presented by: Randy Vince, MD, Society of Urologic Oncology Fellow, Department of Urology, University of Michigan, Ann Arbor, MI 

Co-Authors: Jake Quarles, Michelle Jacobs, Mallory Luke, Samuel Kaffenberger, Simpa Salami, Sanjay Das, Marissa Solorzano, Elena Stoffel, Sofia Merajver, Jason Hafron, and Todd Morgan

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center, Nashville, TN, USA, Twitter: @WallisCJD at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27-28, 2020.