Prognostic Value of Homologous Recombination Deficiency Identified by Comprehensive Genomic Profiling in Incurable Pancreatic Cancer

Comprehensive genomic profiling (CGP) has been reimbursed by Japan’s national health insurance since 2018, yet its practical benefits for patients remain uncertain. To better understand its clinical relevance, we analyzed data from 115 individuals with incurable pancreatic cancer (IPC) who underwent CGP at a Japanese cancer referral hospital between November 2019 and August 2021. Our assessment focused on genomic findings, treatments informed by CGP, and patient survival outcomes. High tumor mutation burden or microsatellite instability (TMB-H/MSI-H) was identified in 6.9% of cases. Mutations in KRAS, TP53, CDKN2A, and SMAD4 were observed in 93.0%, 83.0%, 53.0%, and 25.2% of patients, respectively. Additionally, 21.7% of patients harbored alterations associated with homologous recombination deficiency (HRD). Among those with TMB-H or MSI-H, four patients received pembrolizumab, and two participated in clinical trials. Clinical characteristics did not differ meaningfully between the HRD-mutated and non-mutated groups. Notably, individuals with HRD-related mutations demonstrated significantly longer overall survival (median 749 days) compared with those without such mutations (median 519 days; p = 0.047). Multivariate analysis confirmed HRD-associated alterations as an independent predictor of improved survival. These findings suggest that CGP may offer prognostic insight in IPC, particularly through the detection of HRD-related gene changes, while also supporting the identification of potential therapeutic opportunities.