Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Versus Surgery Without HIPEC for Goblet-Cell Carcinoids and Mixed Adenoneuroendocrine Carcinomas: Propensity Score-Matched Analysis of Centers in the Netherlands and Belgium

Abstract

Background: The value of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneally metastasized goblet-cell carcinoids (GCCs) and mixed adenoneuroendocrine carcinomas (MANECs) is currently unclear. We compared outcomes of CRS-HIPEC to surgery alone for peritoneally metastasized GCCs and MANECs. Patients and Methods: Two cohorts were obtained from the Netherlands Cancer Registry (n = 569): patients with peritoneally metastasized GCCs and MANECs treated with CRS-HIPEC in Dutch and Belgian centers (n = 45), and patients treated with surgery alone. Primary outcome was overall survival (OS). Secondary outcomes were morbidity and hospital mortality. After propensity score matching, OS was compared in univariate and multivariate analyses. A systematic literature review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines from database inception to June 25, 2018. Results: After matching for sex, tumor stage, lymph node stage, and liver metastases, CRS-HIPEC was associated with improved median OS in the combined GCC and MANEC group and the separate GCC subgroup in univariate (GCC + MANEC: 39 vs. 12 months, P <.001; GCC: 39 vs. 12 months, P =.017) and multivariate analysis (GCC + MANEC: hazard ratio 4.27, 95% confidence interval 1.88-9.66, P =.001; GCC: hazard ratio 2.77, 95% confidence interval 1.06-7.26, P =.038). Acceptable grade III-IV morbidity (17.5%) and mortality (0) were seen after CRS-HIPEC. The literature review supported these findings. Conclusion: CRS-HIPEC is associated with substantial survival benefit in patients with peritoneally metastasized GCCs and MANECs compared to surgery alone and is a safe treatment option. These data support centralized care of GCC and MANEC patients with peritoneal spread in expert centers offering CRS-HIPEC.