Peritoneal disseminations from appendiceal vs. colorectal mucinous adenocarcinoma. An Italian multicentric comparative study

Background: We compared baseline characteristics, outcomes and patterns of failure between patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for peritoneal disseminations from appendiceal (MACA) or colorectal mucinous adenocarcinoma (MCRC), in order to assess clinical and prognostical differences. Methods: Prospectively collected data for 402 patients treated for MACA (n = 218) or MCRC (n = 184) in 17 Italian centers were retrospectively analyzed. Results: Colorectal origin was associated with lower peritoneal cancer index (PCI) (P < 0.001), lower rates of signet-ring cells histology (P = 0.016), T4a/b primaries (P < 0.001), negative nodes (P < 0.001), synchronous metastases (P < 0.001), microsatellite stability (P = 0.009), wild-type KRAS (P < 0.001) and BRAF (P < 0.001), but not wild-type NRAS (P = 0.999), incomplete cytoreduction (P = 0.014), and perioperative systemic anticancer treatments (s-ACT) (P < 0.001). Median follow-up was 70.5 months (95% confidence interval [CI] = 45.8-92.3) for MACA, and 40.2 months (95%CI = 35.4-55.2) for MCRC. Five-year overall survival was 58.9% (95%CI = 51.3-67.5) for MACA, and 35.4% (95%CI = 27.1-46.2) for MCRC (P < 0.001). Appendiceal origin correlated with better prognosis at multivariate analysis (hazard-ratio 2.52; 95%CI = 1.50-4.25; P < 0.001). Five-year cumulative incidence of distant relapses was higher for MCRC: 42.6% (95%CI = 30.8-52.4) vs. 28.1% (95%CI = 19.7-35.7) (P = 0.032). Incidence of peritoneal relapse was not different (P = 0.706). PCI correlated with survival in MCRC (P < 0.001), but not in MACA. Perioperative s-ACT correlated with worse prognosis in MACA (P = 0.024), but not in MCRC (P = 0.920). Conclusions: Peritoneal disseminations from MACA are associated with distinct clinical-biological features, better prognosis and lower incidence of systemic relapses, suggesting that MCRC and MACA are different entities. MACA should not be excluded from CRS/HIPEC based only on higher PCI. The role of s-ACT remain unclear.