Apoptotic Marker Analysis in Heated‐Intraperitoneal Chemotherapy Effluent Fluid Is Associated With Prognosis in Patients With Peritoneal Metastases

OBJECTIVE: To evaluate apoptotic markers in tumor cells from hyperthermic intraperitoneal chemotherapy (HIPEC) effluent as a biomarker of treatment effectiveness. BACKGROUND: Cytoreductive surgery (CRS) combined with HIPEC is used to treat peritoneal surface malignancies (PSM), yet no validated method exists to assess HIPEC efficacy in real time. We explored whether apoptosis in residual tumor cells present in post-HIPEC effluent correlates with oncologic outcomes. METHODS: Forty-four patients undergoing CRS-HIPEC were prospectively enrolled. CD45⁻ cells were stained for Annexin-PI by flow cytometry before and after HIPEC. The apoptotic response (Δapop) was defined as the increase in apoptosis post-HIPEC. Clinical and procedural variables were correlated with peritoneal disease-free survival (pDFS). RESULTS: Tumor histologies included colorectal (50%), appendiceal (18.2%), ovarian (15.9%), and gastric (11.4%) primaries. Complete cytoreduction was achieved in 81.8% of patients. Median Δapop = 8.5% (IQR: 0%-37%). Responders had significantly prolonged pDFS (median not reached vs. 16 months; p = 0.04). On multivariable analysis, apoptotic response remained a significant predictor of pDFS (HR = 0.22; 95% CI: 0.05-0.87; p = 0.03), independent of PCI and CCR. CONCLUSIONS: In this pilot study, apoptotic markers in HIPEC effluent are a histology-agnostic assay that correlates with recurrence risk. This biomarker may improve patient selection for adjuvant therapies.