Germline genetic testing of patients with penile carcinoma.

10 Background: Penile carcinoma (PeCa) is a rare malignancy with a mean age at diagnosis of 60 years. PeCa is epidemiologically associated with phimosis, HPV, HIV, tobacco, obesity, Psoralen and ultraviolet A photochemotherapy and lichen sclerosis. However, the prevalence and type of pathogenic germline variants (PGVs) associated with PeCa are unknown. Methods: A retrospective cohort of patients (pts) with PeCa who underwent germline testing (range of genes tested, 1-134) from 10/2016 to 5/2022 at a large commercial laboratory (Invitae) was evaluated. Clinician-reported clinical and demographic information from test requisition forms (TRF) were analyzed and the frequency and type of PGVs was determined. Pts were identified via keywords and/or ICD-10 codes for PeCa, but the final study cohort was limited to those whose diagnosis could be corroborated by details in the TRF and/or accompanying medical records. Pts with other pathologies were excluded. Results: Of the 29 pts who met inclusion criteria, the majority were White (65.5%), with a median age (range) of 62.5 years (36-79) at diagnosis. 44.8% of pts had documented squamous cell carcinoma (SCC) pathology, 55.2% of pts had an additional non-PeCa cancer, and 62.1% of pts had a documented family history of relevant cancers (penile, prostate, breast, ovarian, pancreatic and/or colorectal). Among 29 pts with PeCa, 3 harbored PGVs (10.3%) and 16 (55.2%) had > 1 variants of uncertain significance (VUS) in the absence of a PGV. Of the 3 positive pts, 2 harbored BRCA2 PGVs and one harbored a RAD51C PGV. One pt with a BRCA2 PGV had additional malignancies of the prostate and pancreas. Conclusions: This is the first study to our knowledge reporting PGVs in PeCa. PGVs in DNA repair genes ( BRCA2, RAD51C) were identified in 10.3% of selected high-risk PeCa pts with the majority exhibiting other malignancies or family history of malignancies. Larger cohorts of PeCa patients should be studied in pts with different ethnicities. Nonetheless, these data highlight the potential role of germline testing in selected PeCa pts as a tool to aid in clinical management, cascade testing and potential therapeutic relevance in the future.