Real-world outcomes of genetic testing in a GU genetics clinic and evaluation of current guidelines

• Published in: Journal of clinical oncology Vol. 37; no. 7_suppl; p. 668
• Main Authors: Pace, Annelise, Woodson, Ashley Henriksen, Slack-Tidwell, Rebecca, Daniels, Molly S., Pilie, Patrick Glen, Litton, Jennifer Keating, Hoskovec, Jennifer M., Jonasch, Eric
• Format: Journal Article
• Language: English
• Published: 01-03-2019
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2019.37.7_suppl.668

Abstract only 668 Background: Several known hereditary cancer syndromes confer an increased risk for genitourinary (GU)-related malignancies. Various guidelines indicate when to refer patients to genetic counseling for GU cancers, but there are limited data on the performance of these guidelines in clinical practice, and the association between testing outcome and clinical and familial features that may delineate a heritable syndrome. The purpose of this study is to determine the most common indications for ordering genetic testing in a GU Genetics Clinic and evaluate the relationship between the indication for germline testing and outcome. Methods: An IRB-approved retrospective chart review was performed for 350 patients seen in a GU Genetics Clinic at a single comprehensive cancer center from 2014-2018. Subgroups of patients were formed based on their indication for genetic testing. Exact binomial tests were used to compare the proportion of patients with a positive (pathogenic or likely pathogenic) germline variant for those with vs. without each indication. Results: All patients had a genetic evaluation due to a personal or family history of GU cancer. The majority (324 of 350, 92.5%) were evaluated for either renal cell carcinoma (RCC) or prostate cancer (PrCa). Among patients seen for RCC-related evaluation (n = 159), 23 patients (14.5%) tested positive. Meeting published clinical criteria for a hereditary RCC syndrome significantly predicted positive testing ( P< 0.001). No other indication for testing, including RCC diagnosis ≤ 46 years, predicted for positive germline genetic test results. No positive patients were identified by age of RCC onset alone. Among patients seen for PrCa-related evaluation (n = 173), 13 (7.5%) individuals tested positive; all positive variants were in ATM or BRCA2. A single patient (1/13) was identified by metastatic PrCa status alone. Conclusions: Our data suggest current algorithms lack specificity for selecting individuals with RCC or PrCa at risk for germline mutations, and need to be revised. Evaluation of pedigrees and identifying presence of syndromic features are essential and increase the probability of identifying individuals at risk for harboring a germline mutation.