Locoregional Control from Complete Peritoneal Cytoreduction in Patients with Extraperitoneal Colorectal Cancer Metastases: An Entropy Balanced Analysis

PURPOSE: We evaluated the role of complete cytoreductive surgery (CRS) for locoregional disease control in patients with colorectal cancer with peritoneal metastases (CRC-PM) and concurrent extraperitoneal metastases (EPM). METHODS: Institutional data identified patients with CC-0/1 CRS for CRC-PM. Patients with peritoneal disease only (PDO) were compared with those with concomitant EPM. Co-primary outcomes were progression-free survival (PFS) and peritoneal progression-free survival (p-PFS). The secondary outcome was overall survival (OS). Covariate imbalance was addressed using entropy balancing. Survival was analyzed using a weighted Cox proportional hazards model. Subgroup analyses were performed to identify favorable prognostic groups. RESULTS: In total, 83 patients were included: 31 (37.4%) had EPM. Baseline characteristics were comparable. Within the EPM cohort, liver-only metastases were most common (58%), followed by lung-only metastases (26%). EPM were managed at index CRS in 61%, before CRS in 19%, and deferred or untreated in 19% of patients. Unadjusted analyses demonstrated comparable median OS (PDO vs. EPM: 39 vs. 34 months, p = 0.551) and median p-PFS (PDO vs. EPM: 17 vs. 15 months, p = 0.346) but longer median PFS in the PDO group (14 vs. 5 months, p<0.001). After entropy balancing, patients with EPM had worse OS (31.6 vs. 38.7 months; hazard ratio [HR] 2.12; 95% confidence interval [CI] 1.02-4.37; p < 0.05) and PFS (5.0 vs.12.8 months; HR 2.7; 95% CI 1.58-4.5; p < 0.001) but similar p-PFS (13.4 vs.14.9 months; HR 1.10; 95% CI 0.58-1.77; p = 0.622). Subgroup analyses demonstrated comparable OS and p-PFS for patients with PDO and those with single-site liver or lung EPM. CONCLUSION: Complete CRS provides durable locoregional disease control in patients with EPM.