Abstract 3372: Clinical genetic testing results in metastatic prostate cancer patients
Authors: Crawford Taylor , Barrett Emanuel , Al-Saleem Tara , Tayeb Maliha , Symecko Heather , Orr Caitlin , Narayan Vivek , Takvorian Samuel , Parikh Ravi B. , Wong Yu-Ning , Robinson Kyle , Aiello Lisa B. , Wolfe Catherine , Mann Derek , Spielman Kelsey , Domchek Susan M. , Maxwell Kara N. 
Published: March 2024

Background: A proportion of prostate cancers (PCa) are hereditary, driven by likely pathogenic/pathogenic germline variants (PGVs) in DNA repair genes. PGVs in BRCA2 contribute to aggressive prostate cancer biology and overall poorer survival. Genetic testing and targeted sequencing panels help identify PGV carriers who are susceptible to aggressive PCa and may be candidates for targeted therapy with PARP inhibitors. Prior research suggested a high rate of 10-20% of metastatic PCa (mPCa) patients have PGVs in DNA repair genes; however, many of these studies reported highly selected research cohorts. The real-world rate of DNA repair PGVs and whether any genotype-phenotype correlations exist in broader, more racially diverse clinical populations are not well understood.

Patients and Methods: We studied two prospective cohorts of males with PCa who presented for genetic testing due to meeting NCCN personal history genetic testing criteria for prostate cancer (metastatic or high risk/very high risk localized). We report PGV frequencies of mPCa patients who underwent genetic testing in a point of care model at the Basser Center within Penn Medicine (Penn-POC, n=596), and a cancer genetics practice at the Corporal Michael Crescenz VA Medical Center in Philadelphia (VA-GT, n = 171). PGVs were identified in ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PMS2, TP53.

Results: The Penn-POC and VA-GT cohort included 437 (73.3%) and 59 (34.5%) self-identified white patients, respectively, and 121 (20.3%) and 107 (62.6%) self-identified black patients, respectively. In the Penn-POC and VA-GT cohorts, 7.2% and 7.6% patients were found to carry a PGV, respectively, and 11.9% and 18.1% of patients had variants of uncertain significance (VUS), respectively. The most common PGVs in the Penn-POC cohort were in BRCA2 (2.2%), ATM (1.9%), and BRCA1 (1.3%). The most common PGVs in the VA-GT cohort were in BRCA2 (2.9%), ATM (1.1%), and CHEK2 (1.2%). PGV rates were not statistically different between self-identified white and black patients in either cohort (Penn-POC p= 0.4036; VA-GT p=0. 0.4061). Overall PGV frequencies between the Penn-POC and VA-GT cohorts are not statistically different. There is a correlation between carrier status and age at diagnosis with a significant difference between carriers and non-carriers (p=0.0433) as well as with family history of first degree relatives with PCa (p=0.0184). However, there was not a significant correlation between carrier status and clinical stage at diagnosis, Gleason grade group, or other clinical variables.

Conclusions: We report a lower rate of DNA repair PGVs in two prospectively ascertained, racially diverse cohorts of mPCa patients, approximately 7%, compared to the previously reported rates of 10-20%. Our results suggest age and family history, but not other pathological variables are clinical predictors for carrying a PGV in mPCa patients.

Citation Format: Taylor Crawford, Emanuel Barrett, Tara Al-Saleem, Maliha Tayeb, Heather Symecko, Caitlin Orr, Vivek Narayan, Samuel Takvorian, Ravi B. Parikh, Yu-Ning Wong, Kyle Robinson, Lisa B. Aiello, Catherine Wolfe, Derek Mann, Kelsey Spielman, Susan M. Domchek, Kara N. Maxwell. Clinical genetic testing results in metastatic prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3372.