Improved survival with immunotherapy for microsatellite unstable colorectal cancer with peritoneal metastases

Abstract Background KEYNOTE‐177 demonstrated that immunotherapy was superior to chemotherapy for microsatellite‐instability‐high (MSI‐high) metastatic colorectal cancer. Colorectal cancer with peritoneal metastases (CRPM) has a poorer prognosis than other metastatic sites, with an unclear role of immunotherapy. We evaluated trends in immunotherapy use and overall survival (OS). Methods Patients with CRPM and MSI testing were identified in the National Cancer Database (2016−2020). We evaluated immunotherapy use by year and associated patient/hospital factors. OS was compared for immunotherapy versus chemotherapy, cytoreductive surgery (CRS), and immunotherapy plus CRS. Results Among 15 322 CRPM patients, 7072 (46.2%) patients had documented MSI testing, with 819 (11.6%) MSI‐high. Ninety‐eight MSI‐high patients received immunotherapy alone (12.3%), increasing from 0% in 2016 to 19.1% in 2020 ( p < 0.01). On multivariable analysis, only higher comorbidity was associated with immunotherapy (OR: 2.83 [1.22−6.52]). Two‐year OS with immunotherapy versus chemotherapy was 64.2% versus 54.1% ( p < 0.05). In patients receiving CRS plus systemic therapy ( N = 96), 2‐year OS was 68.4%. Among patients who underwent immunotherapy and CRS versus immunotherapy alone, 2‐year OS was 80.0% versus 60.0% ( p = 0.14). Conclusions Immunotherapy was associated with significantly better survival compared to chemotherapy in MSI‐high CRPM. Two‐year OS with systemic + CRS was 68.4%. Despite its role in guiding treatment, MSI testing remains low for these patients.