Immunotherapy in rectal cancer patients-a propensity score matched analysis of the National Cancer Database.

BACKGROUND: Rectal cancer patients with microsatellite instability (MSI-H) are candidates for immunotherapy. However, there is little evidence on its effect on overall survival (OS).

METHODS: Retrospective analysis of stage II-IV rectal adenocarcinoma patients in the National Cancer Database (NCDB) between 2010 and 2019. Propensity score matching was adjusted for baseline and treatment confounders. The cohort was divided into patients who received immunotherapy and matched controls. The primary outcome was OS.

RESULTS: 5175/206,615 (2.5%) patients with rectal adenocarcinoma underwent immunotherapy. These patients were younger (58 vs 62 years; p < 0.001), more often male (64.4% vs 61.7%; p < 0.001), were more likely to have private insurance (50.8% vs 43.4%; p < 0.001), more metastatic disease at presentation (clinical TNM stage IV-80.8% vs 23.3%; p < 0.001), presented with larger tumors (median: 5 cm vs. 4.2 cm; p < 0.001) and less often underwent surgery (33.7% vs. 69.9%; p < 0.001), radiation therapy (21.5% vs 57.4%; p < 0.001), and standard chemotherapy (38.1% vs 61%; p < 0.001) than controls. After matching, 488 patients were in each group. OS was significantly shorter in the immunotherapy group (mean survival: 56.4 months (95% CI: -53.03-59.86)) compared to controls (mean survival: 70.5 months (95% CI: -66.15-74.92) (p = 0.004)). Cox regression analysis of factors associated with OS demonstrated that immunotherapy was associated with increased mortality (HR 2.16; 95% CI: 2.09-2.24; p < 0.001). After clinical staging stratification, immunotherapy was associated with improved OS in stage IV (HR 0.91, 95% CI: 0.88-0.95; p < 0.001) but lower survival in stage II (HR 2.38; 95% CI: 2.05-2.77; p < 0.001) and stage III (HR 2.43; 95% CI: 2.18-2.7; p < 0.001) patients.

CONCLUSION: Immunotherapy showed modest increase in OS in stage IV metastatic rectal cancer. OS was significantly lower in stage II-III disease treated with immunotherapy.