Pathologist-Driven Reflex Somatic Tumor DDR Testing in Localized Prostate Cancer. Susan Prendeville and Shamini Selvarajah

Our host discusses with Drs. Prendeville and Selvarajah, from the departments of Laboratory Medicine and Pathobiology at the University of Toronto, their recent study on Pathologist-Driven somatic testing for DNA Damage Repair (DDR) in prostate carcinoma (PCa).

516 FFPE samples from metastatic and localized high risk PCa cases including needle biopsies, TURP and RP specimens were tested using a custom NGS panel of 83 cancer predisposition genes encompassing 4 Homologous Recombination Repair (HRR) genes [BRCA1/2, ATM, PALB2] and 4 Mismatch Repair (MRR) [MLH1, MSH2, MSH6, PMS2]. 13.9% of patients had at least one AMP/ASCO/CAP tier I or tier II variant, whereas 21.5% patients had a tier III variant. Tier I/II variant(s) were identified in 27% of metastatic biopsy samples and 13% of primary samples.

The presence of a tier I/II variant was not significantly associated with the grade group (GG) or presence of intraductal (IDC-P) /cribriform carcinoma in the primary tumor and therefore may not be reliable to guide patient selection.