Survival Benefit of Immunotherapy in Patients With Stage IV Microsatellite Stable Rectal Cancer: A Propensity-Score Matched Analysis

This study aimed to assess factors associated with overall survival (OS) in patients with microsatellite stable (MSS) stage IV rectal cancer treated with immunotherapy. In this retrospective review of the NCDB (2015-2021), patients with MSS stage IV rectal adenocarcinoma were divided into immunotherapy and control groups, and propensity-score matched and compared. Multivariable Cox regression analysis was performed to assess the effect of immunotherapy and KRAS genotype on OS. Of 6489 included patients (64.6% males), immunotherapy was given to 47.9%. After matching for age, insurance type, liver metastases, surgery, radiation therapy, and chemotherapy, there were 2422 patients in each group. In the matched cohort, immunotherapy was associated with a similar median OS to the control group [31.8 (95% CI: 27.8-32.2) months vs 29.7 (95% CI: 27.8-32.2) months, P = 0.062]. Immunotherapy was not independently associated with improved OS (HR: 0.88, 95% CI: 0.69-1.14, P = 0.341) but was associated with longer median OS in black patients (25.8 vs 19.1 mo, P = 0.019), patients with bone metastases (22.1 vs 10.7, P < 0.001) and with KRAS mutation (27.4 vs 24.3 mo, P = 0.003). There was no survival benefit from immunotherapy when combined with radical resection, radiation therapy, or chemotherapy. In conclusion, immunotherapy was associated with a modest increase in OS of MSS stage IV rectal cancers, but not independently associated with improved survival. Black patients with bone metastases and KRAS mutations may have survival benefit from immunotherapy. Increased OS with immunotherapy was noted only in patients who did not have surgery, radiation, or chemotherapy. These results seem somewhat disappointing given the enthusiasm for immunotherapy.