Determinants of Long-Term Survival versus Early Failure After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Comparative Analysis of Two Extreme Phenotypes.

BACKGROUND: Cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and perioperative chemotherapy can render colorectal peritoneal metastases (CRC-PM) a curative-intent disease in selected patients. However, the factors that separate long-term survivors from patients who fail early have rarely been examined by direct comparison. We compared the two extreme outcome phenotypes. METHODS: In a single-center, retrospective, comparative cohort (2007-2025), consecutive patients undergoing CRS-HIPEC for CRC-PM were identified. Long survivors (overall survival [OS] ≥36 months; n=47) and early-failure patients (OS ≤6 months; n=61) were compared directly (n=108); the early-failure group was defined by overall survival ≤6 months. Univariable comparison and multivariable binary logistic regression were used for the two-phenotype comparison; time-to-event (Kaplan-Meier and Cox) modelling was restricted to the full cohort (n=244) to avoid conditioning on the outcome. Analyses were performed in SPSS v29. RESULTS: High PCI (≥14) was independently associated with early-failure group membership, and ostomy formation was also associated with early failure, most likely as a surrogate for rectal/pelvic disease (logistic regression: OR 6.21 and 5.38, respectively). In the full cohort, high PCI (HR 2.64; 95% CI 1.25-5.55) was independently associated with shorter survival, as was ostomy formation (HR 2.69; 95% CI 1.28-5.66), though the latter is most likely a surrogate for rectal/pelvic disease. Compared with early-failure patients, long survivors had lower tumor burden, more frequent complete cytoreduction (93.6% vs 78.7%), a numerically but not significantly higher rate of neoadjuvant chemotherapy (66.0% vs 49.2%; p=0.081), no grade ≥III complications, and no anastomotic leak (0% vs 11.5%). CONCLUSIONS: Low peritoneal tumor burden, complete cytoreduction, and an uncomplicated postoperative course distinguish long-term survivors, whereas high peritoneal tumor burden marks early failure; ostomy formation is associated with early failure but most likely as a surrogate for rectal/pelvic disease rather than an independent factor. These findings reinforce the central role of patient selection and complete cytoreduction, which is best regarded not as demolition surgery but as surgical architecture. SYNOPSIS: In this comparative cohort of patients undergoing cytoreductive surgery and HIPEC for colorectal peritoneal metastases, high peritoneal tumor burden distinguished early failure from long-term survival, and ostomy formation was associated with early failure (most likely as a surrogate for rectal/pelvic disease), whereas low PCI, complete cytoreduction, and an uncomplicated postoperative course characterized long survivors.