SES AUA 2021: Results from Targeted Germline Sequencing in Men on Active Surveillance for Prostate Cancer

( Prostate cancer remains the most commonly diagnosed malignancy for men in the United States. Genetic inheritance does portend significant risk in developing aggressive prostate cancer, yet there is limited understanding of whether germline alterations play a significant role in localized disease for men on active surveillance. At the Southeastern Section of the AUA 2021 virtual meeting, fourth-year medical student Scott Brimley and colleagues presented results of their study assessing whether germline screening in patients presenting for active surveillance with low risk prostate cancer could provide prognostic information regarding risk of pathologic upgrading or disease progression.

From a prospectively maintained IRB-approved cohort of men with localized low or favorable intermediate-risk prostate cancer electing active surveillance for their primary treatment modality, the authors queried patients who had obtained targeted germline screening. Patients were subsequently followed with biannual PSA, annual DRE and MRI, and biopsies based on these findings.

In this study, there were 40 men identified with targeted germline screening using the Invitae targeted platform. There were 15 patients that had at least one family member with a history of prostate cancer, and 33 had at least one family member with a history of any malignancy. Among these 40 patients, 15 (37.5%) had DNA alterations detected by the Invitae report, and 6 had a pathologic DNA mutation. There were 8 men without DNA alterations that were upgraded but remained on active surveillance. Among those with non-pathologic DNA alterations, 5 patients were upgraded and among those with pathologic DNA mutations, 4 upgraded. At a median follow-up of 66.4 months, 17 (42.5%) patients eventually underwent local curative therapy, with a similar rate in both germline mutation and non-mutation cohorts. 


The following concluding statements were made by Scott Brimley regarding germline sequencing among men who are candidates for active surveillance: 

  • Among 40 patients who underwent germline sequencing while on active surveillance for their low risk prostate cancer, a high rate of variant of unknown significance were detected 
  • Germline sequencing demonstrates a high rate of mutational burden in patients presenting for active surveillance
  • Further evaluation is needed to better understand the true prevalence of germline aberrations in this population of men who otherwise would be candidates for active surveillance

Presented by: Scott Brimley, BS, University of Tulane School of Medicine, New Orleans, LA
Co-Authors: Jacob Greenberg, B.S., Elisa Ledet, PhD, Charlotte Manogue, M.P.H., Oliver Sartor, M.D., Louis Krane, M.D.

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md during the 85th Annual Southeastern Section of the American Urological Association, April 23-24, 2021
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