Mutational profiles and prognostic impact in colorectal and high-grade appendiceal adenocarcinoma with peritoneal metastases

Background: Next-generation sequencing (NGS) personalizes cancer treatments. In this study, we analyze outcomes based on NGS testing for colorectal cancer (CRC) and high-grade appendiceal adenocarcinoma (HGA) with peritoneal metastases. Methods: Retrospective review of genomic analyses and outcomes in patients with CRC or HGA with peritoneal metastases at a high-volume center from 2012 to 2019. Results: Ninety-two patients (57 CRC, 35 HGA) were identified. Overall survival was longer for CRC (52.8 vs. 30.5 months, p = 0.03), though rates of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) were similar. Multiple genes were more frequently mutated in CRC, including KRAS (51% vs. 29%, p = 0.04), TP53 (47% vs. 20%, p < 0.01), and APC (46% vs. 6%, p < 0.01). For CRC, multivariate regression showed an increased hazard ratio (HR) with increasing peritoneal cancer index (1.06 [1.01–1.11], p = 0.02) and a decreased HR following CRS/HIPEC (0.30 [0.11–0.80], p = 0.02). PIK3CA mutation associated with significantly increased HR (3.62 [1.06–12.41], p = 0.04), though only in non-CRS/HIPEC patients. Multivariate analysis in the HGA group showed a benefit following CRS/HIPEC (0.18 [0.06–0.61], p = 0.01) and for mucinous disease (0.38 [0.15–0.96], p = 0.04), while there was an increased HR with TP53 mutation (6.89 [2.12–22.44], p < 0.01). Conclusion: CRC and HGA with peritoneal spread have distinct mutational profiles. PIK3CA and TP53 mutations are associated with survival for CRC or HGA with peritoneal metastases, respectively.