Main Session
Sep
29
PQA 06 - Genitourinary Cancer, Gynecological Cancer, and Health Care Access and Engagement
3337 - Assessing the Prevalence of Pathogenic Germline Variants in Prostate Cancer Patients Managed with Radiation Therapy
Presenter(s)
Adetolani Odogiyon, BS - Massachusetts General Hospital, Winchester, MA
A. Odogiyon1, G. E. Cerrato1, V. Nambi1, K. Salari2, D. T. Miyamoto3, J. A. Efstathiou4, and S. C. Kamran5; 1Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, 2Department of Urology, Mass General Brigham, Harvard Medical School, Boston, MA, 3Massachusetts General Hospital and Harvard Medical School, Boston, MA, 4Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 5Massachusetts General Hospital, Boston, MA
Purpose/Objective(s):
Up to 10% of prostate cancers (PCa) can be attributed to a cancer susceptibility gene. Germline genetic testing (GGT) is suggested for PCa patients (pts) with metastatic/high-risk disease, aggressive histology, or significant family cancer history (FHx). To assess the prevalence of actionable pathogenic germline variants (PGVs) in PCa, we evaluated pts treated with radiation therapy (RT) with available sequencing. We also evaluated guideline-directed GGT referral patterns to understand how many eligible pts were captured.Materials/Methods:
We evaluated 454 PCa pts treated with RT at our institution between 2010-2024 who had germline whole exome sequencing (WES) available. WES data was annotated with Ensembl Variant Predictor, with ClinVar and OncoKB for variant pathogenicity. 111 high-risk (HR) genes of interest were derived from Ambry and Invitae genetic testing lists. Clinical demographics, guideline-directed GGT history, and cancer FHx among close blood relatives were collected. Statistics were performed by Chi Square and Mann Whitney tests.Results:
Clinical data at diagnosis for the 454 pts were evaluated (Table). Of these, 57 (13%) were referred for guideline-directed GGT. On formal testing, seven patients had PCa-associated PGVs [FANCA (n=1), BRCA2 (n=3), BRCA1 (n=2), and TP53 (n=1)], and 3 had concordant PGV with WES [BRCA2 (n=2), FANCA (n=1)]. Of the 50 pts with negative testing, one had a PGV on WES (TP53). From the 397 pts not referred, 195 (49%) met criteria for genetic testing due to: FHx (43%), high-risk/metastatic disease (51%), aggressive histology (6%). Three pts had PGVs, one with each of BRCA1, BRCA2, and FANCF. Of the 203 pts (51%) who did not meet the criteria for testing, two pts had PGVs (ATM, TP53). The patient with ATM had low-risk disease, while the pt with TP53 had intermediate-risk. Overall, 7/57 (12%) pts had PGVs via formal GGT, while 5/397 (1%) pts not referred had PGVs via WES (p < 0.001). Of these 5 not referred, 3 pts would have met GGT criteria. The prevalence of PGVs was higher among patients with a positive FHx vs those without (7% vs 1%, p < 0.006).Conclusion:
The prevalence of germline HR gene mutations in this RT-treated PCa cohort was low. The majority were identified via formal GGT. Although 49% of pts not referred met guideline criteria, only 3 more pts had PGVs. Despite an argument for universal GGT, formal referral captures most pts with PGVs. Improved awareness may increase guideline-directed referrals for GGT and better identify pts with PGVs. Table| No. (%) No PGV (n=441) | No. (%) Any PGV (n=13) | p-val | |
| Age, median (range) | 67 (41, 89) | 68 (54, 76) | 1.0 |
| Stage | 0.84 | ||
| Localized Metastatic | 400 (91) 41 (8) | 12 (92) 1 (8) | |
| Localized risk group (n=412) | 0.99 | ||
| Low Intermediate High | 94 (23) 220(55) 86 (21) | 2 (17) 7 (58) 3 (25) | |
| Histology | 0.17 | ||
| Intraductal Cribriform None | 11 (2) 25 (6) 405 (92) | 1 (8) 2 (15) 10 (77) | |
| Family Hx | 0.006 | ||
| Positive Negative | 143(32) 298 (68) | 9 (69) 4 (31) |