Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) of Extraperitoneal Abdominal Disease, is it Appropriate?

Abstract

Introduction: Cytoreductive surgery-hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) candidates often have extraperitoneal abdominal disease. Current expert peritoneal surface malignancy (PSM) guidelines recommend that the presence of extraperitoneal disease is a contraindication to CRS-HIPEC.

Methods: We conducted a retrospective review of our institutional appendiceal and colorectal CRS-HIPEC registries. Two study cohorts were constructed: (1) cytoreduction with extraperitoneal abdominal disease, and (2) cytoreductions limited to peritoneal structures alone. The primary study outcome was survival. Subgroup analysis was based on the primary tumor and completeness of cytoreduction.

Results: Overall, 864 CRS-HIPEC cases were evaluated, consisting of 578 appendiceal primaries and 286 colorectal cancers. The extraperitoneal cohort included 101 patients, with 763 patients in the non-extraperitoneal group. The median follow-up time was 13.18 years. The main analysis showed no significant differences in survival times. For overall survival (OS) there was a mean OS time of 5.87 years and a median OS time of 4.43 years for extraperitoneal cytoreductions compared with a mean of 5.90 years and a median of 4.76 years for non-extraperitoneal cytoreductions (p = 0.955). Five-year OS rates did not differ at 49.1% versus 49.5% (odds ratio [OR] 1.036, 95% confidence interval [CI] 0.671-1.597, p = 0.874). Disease-free survival (DFS) times showed a mean of 4.40 years and a median of 1.93 years for extraperitoneal cases versus a mean of 5.44 years and a median of 3.05 years for non-extraperitoneal cases (p = 0.210). Five-year DFS rates also showed no differences (OR 0.894, 95% CI 0.476-1.681, p = 0.728). No significant differences in progression-free survival (PFS)Pp times (p = 0.061) were reported. Multivariate Cox regression analysis indicated that extraperitoneal CRS was not an independent predictor of OS (hazard ratio [HR] 1.281, 95% CI 0.885-1.854, p = 0.190), DFS (HR 1.087, 95% CI 0.694-1.701, p = 0.716), or PFS (HR 0.650, 95% CI 0.243-1.738).

Conclusion: We conducted the largest analysis evaluating extraperitoneal cytoreductions, with no significant differences in almost all survival outcomes. We propose that the presence of extraperitoneal abdominal disease is not a contraindication to proceeding with CRS-HIPEC.