Abstract
BACKGROUND: Mismatch-repair deficiency (dMMR) predicts worse chemoresponsiveness but better survival in early-stage colorectal adenocarcinoma. This study examined metastatic colorectal and appendix cancers with and without peritoneal metastasis (PM) in the National Cancer Database (NCDB), hypothesizing that dMMR tumors show better survival. METHODS: Stage 4 colon, rectum, and appendix cancers (2010-2016) were identified in the NCDB (including goblet cell carcinoids, excluding neuroendocrine tumors). Stage 4 disease without liver, bone, brain, lung, or distant nodal metastases defined PM. Fisher's exact tests were used to compare proportions, and Kaplan-Meier analysis was used to evaluate survival. RESULTS: Of 130,125 stage 4 colon, rectum, and appendix cancers, 27,848 (21.4%) had PM. Appendix primary tumors had PM more commonly than colon or rectum cancer (83.6% vs. 20.6% and 12.1% of stage 4 cases; p < 0.0001). More PM patients had MMR testing than patients with other metastasis (OM) (21.4% vs. 16.1%), and testing increased from 9.6% in 2010 to 26.3% in 2016 (both p < 0.0001). Among the PM patients, MMR testing was least common for appendix cancers (9.0%). When tested, PM patients more often had dMMR (22.9% [1122/4900] vs. 15.4% [2532/16,495] of OM patients; p < 0.0001). Colon primary tumor had dMMR most frequently (25.0% vs. 14.6% and 14.5% for rectal and appendix tumor; p < 0.0001). Most PM patients received chemotherapy (66.2%). Immunotherapy use increased over time (1.1% of PM diagnoses in 2010 vs. 20.8% in 2016). For MMR-tested stage 4 patients, dMMR correlated with worse survival (median OM, 19.7 vs. 23.9 months, p < 0.0001; median PM, 19.9 vs. 24.6 months, p = 0.035). CONCLUSIONS: The NCDB showed dMMR predicting worse survival for stage 4 colorectal cancers with and without PM and dMMR existing in 14.5-25% of tested patients, suggesting that increased attention to MMR testing in stage 4 colorectal and appendix cancers can identify many patients who could potentially benefit from immunotherapy.