Somatic Tumor Testing in Prostate Cancer: Experience of a Tertiary-Care Center Including Pathologist-Driven Reflex Testing of Localized Tumors at Diagnosis

Somatic tumor testing in prostate cancer (PCa) can guide treatment options by identifying clinically actionable variants in DNA damage repair (DDR) genes, including acquired variants not detected by germline testing alone. Guidelines currently recommend performing somatic tumor testing in metastatic PCa, while there is no consensus on the role of testing in regional disease and the optimal testing strategy is involving. This study evaluates the frequency, distribution, and pathologic correlates of somatic DDR mutations in metastatic and localized PCa following the implementation of pathologist-driven reflex testing at diagnosis. A cohort of 516 PCa were sequenced using a custom NGS panel including homologous recombination repair (HRR) and mismatch repair (MMR) genes. Variants were classified based on the AMP/ASCO/CAP guidelines. In total 183 (35.5%) patients had at least one variant: 72/516 (13.9%) had at least one Tier I or Tier II variant while 111/516 (21.5%) had a Tier III variant. Tier I/II variant(s) were identified in 27% (12/44) of metastatic biopsies and 13% (61/472) of primary samples. Overall, 12% (62/516) of patients had at least one Tier I/II variant in a HRR gene while 2.9% (10/516) had at least one Tier I/II variant in a MMR gene. The presence of a Tier I/II variant was not significantly associated with the grade group (GG) or presence of intraductal/cribriform carcinoma in the primary tumor. Among 309 reflex-tested hormone-naïve primary tumors, Tier I/II variants were identified in 10% (31/309) of cases: 9.2% (9/98) GG2; 9% (9/100) GG3; 9.1% (4/44) GG4 and 13.4% (9/67) GG5 cases. Our findings confirm the utility of somatic tumor testing to detect variants of clinical significance in PCa and provide insights that can inform the design of testing strategies. Pathologist-initiated reflex testing streamlines the availability of the results for clinical decision-making, however pathologic parameters such as grade group and intraductal/cribriform carcinoma may not be reliable to guide patient selection.