Is CRS-HIPEC Still Indicated in Patients With Extraperitoneal Disease?

Introduction: The role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with extraperitoneal disease (EPD) is controversial. Methods: Among patients with peritoneal metastases from appendiceal cancer (AC) and colorectal cancer (CRC) who underwent CRS-HIPEC, those with EPD (liver, lung, or retroperitoneal lymph nodes [RP LN]) were retrospectively compared to those without EPD. Overall (OS) and recurrence-free survival (RFS) analyses were performed before/after propensity score matching (PSM). Results: Among 1341 patients with AC (64%) or CRC (36%) who underwent CRS ± HIPEC, 134 (10%) had EPD whereas 1207 (90%) did not. EPD was located in the lungs (47%), RP LN (28%), liver (18%), or multiple (6%). Patients with EPD experienced worse median OS (34 versus 63 mo; P = 0.002) and RFS (12 versus 19 mo; P < 0.001). On a multivariable analysis, EPD was associated with worse RFS (P = 0.003), but not OS (P = 0.071). After PSM, the association of EPD with OS (P = 0.204) and RFS (P = 0.056) was no longer significant. In the multivariable analysis of the PSM cohort, EPD was not associated with OS (P = 0.157) or RFS (P = 0.110). Conclusions: The findings of this large retrospective multi-institutional study suggest that EPD alone, while a negative prognostic indicator, should not be considered an absolute contraindication to CRS ± HIPEC for otherwise well-selected patients with peritoneal surface malignancies. Further research is needed to delineate whether location of EPD influences OS and RFS following CRS-HIPEC.