(UroToday.com) The 2022 EAU annual meeting featured a session on improvements in metastatic prostate cancer focusing on imaging and treatment, including a presentation by Dr. Roderick Clark discussing the lifetime risk of prostate cancer death among high-risk germline mutation carriers. Indeed, prostate cancer is a leading cause of death, ranking second only to lung cancer in male cancer deaths. Approximately one in eight men who are diagnosed with prostate cancer will die of it. It has been well established that certain germline pathogenic variants confer both an increased risk of being diagnosed with prostate cancer and dying of prostate cancer. Contemporary data demonstrate that mutations that disrupt the function of genes involved in repairing DNA damage are associated with aggressive prostate cancer. The objective of this study presented by Dr. Clark at EAU 2022 was to estimate the prostate cancer-specific mortality burden among individuals carrying high-risk germline mutations.
This study included a Bayesian estimation of prostate cancer metastases and mortality probability. Prior estimates for the prevalence of germ-line mutations and the risks of metastases and death were derived from a review of the literature. Dr. Clark and colleagues accounted for genetic anomalies in BRCA1, BRCA2, ATM, and CHEK2. The primary outcomes were prostate specific survival and metastases-free survival. Sensitivity analyses were conducted to test the effects of uncertainty in prior estimates.
The lifetime probability of developing metastatic prostate cancer varied from 5% for ATM carriers to 64% for BRCA2 carriers. Furthermore, the probability of dying of prostate cancer varied from 6.7% for BRCA1 carriers to 60% for BRCA2 carriers. The following table demonstrates the lifetime probability of developing metastatic disease by germline mutation:
and among BRCA 2 mutation carriers:
Dr. Clark concluded his presentation discussing the lifetime risk of prostate cancer death among high-risk germline mutation carriers with the following take home points:
- This is the first study to estimate lifetime risk of metastatic disease and death among carriers with high-risk mutations
- In particular, patients with a BRCA2 mutation experience an extremely high risk of prostate cancer death
- Novel prevention strategies should be encouraged within this population
Presented by: Roderick Clark, MD, University of Toronto, Dept. of Surgery, Toronto, Canada
Co-Authors: Lajkosz L.1, Ken M.1, Thain E.1, Kim R.2, Fleshner N.1
Affiliations: 1University of Toronto, Dept. of Surgery, Toronto, Canada, 2University of Toronto, Dept. of Genetics, Toronto, Canada
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 European Association of Urology (EAU) Annual Hybrid Meeting, Amsterdam, NL, Fri, July 1 – Mon, July 4, 2022.