PM17 - Mismatch Repair Deficiency is Associated with Worse Survival in Colorectal/Appendiceal Cancers with Peritoneal Metastases

Introduction: Mismatch-repair deficiency (dMMR) predicts worse chemoresponsiveness but better survival in early-stage colorectal adenocarcinoma. We examined metastatic colorectal/appendix cancer with and without peritoneal metastasis (PM) in the National Cancer Database (NCDB), hypothesizing that dMMR tumors show improved survival.

Methods: Stage-IV colon/rectum/appendix cancers (2010-2016) were identified in NCDB (goblet cell carcinoids included; neuroendocrine tumors excluded). Stage-IV disease without liver, bone, brain, lung, or distant nodal metastases defined PM. Chi-squared tests compared proportions, Kaplan-Meier evaluated survival.

Results: Of 130,125 stage-IV colon/rectum/appendix cancers, 27,848 (21.4%) had PM. Appendix primaries more commonly had PM versus colon or rectum (83.6% of stage-IV cases vs. 20.6%, 12.1%, p<0.0001). More PM patients had MMR-testing than non-PM patients (21.4% vs. 16.1%), and testing increased from 9.6% in 2010 to 35.8% in 2016 (both p<0.0001). Among PM patients, MMR-testing was least common for appendix cancers (9.0%). When tested, PM patients more often had dMMR (1122/4900, 22.9% vs. 2532/16495, 15.4% of non-PM, p<0.0001). dMMR occurred most commonly with colon primaries (25.0% vs. 14.6 and 14.5%, rectal and appendix, p<0.0001). Most PM patients received chemotherapy (78.3%). Immunotherapy use increased over time (1.1% of 2010 PM diagnoses to 20.8% in 2016). In MMR-tested stage-IV patients, dMMR correlated with worse survival (non-PM median 19.7 vs. 23.9 months, p<0.0001; 19.9 vs. 24.6 months for PM, p=0.035).

Conclusions: In NCDB, dMMR predicted worse survival for stage-IV colon/rectum/appendix cancers with and without PM. dMMR existed in 14.5-25% of tested patients, suggesting that increased attention to MMR-testing in stage-IV colorectal/appendix cancers can identify many patients who could potentially benefit from immunotherapy.