Perioperative chemotherapy in patients with grade 2 or 3 appendiceal cancer undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): A real-world data analysis.

Abstract

e15522 Background: CRS with HIPEC is an established option for selected appendiceal cancers with peritoneal metastases. Current guidelines recommend neoadjuvant chemotherapy for high-grade disease and consideration of adjuvant therapy. However, recent studies have shown conflicting results regarding perioperative chemotherapy on overall survival (OS) and progression-free survival (PFS), with mixed signals suggesting both benefit and harm. In this study, we aim to investigate the effect of perioperative chemotherapy in AJCC grade 2 or 3 appendiceal cancers undergoing CRS/HIPEC. Methods: We performed a retrospective review of all grade 2 or 3 appendiceal cancer cases from a prospectively collected database of CRS/HIPEC cases performed at the University of Pittsburgh Medical Center between May 2001 and November 2024. Perioperative chemotherapy was defined as any chemotherapy given within 3 months before or after CRS/HIPEC procedures. Patient characteristics including age, gender, peritoneal cancer index (PCI) score, and completeness of cytoreduction (CC) score were collected. Survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards model. Results: A total of 340 patients were included and divided into two groups: no perioperative chemotherapy (i.e., NPC group, n = 128) and perioperative chemotherapy (i.e., PC group, n = 212) groups. No significant difference in baseline characteristics was found between the two groups. We found that NPC group had significantly better OS and PFS compared to PC group (OS univariate HR 0.68, 95%CI 0.50-0.92, p = 0.013; OS multivariate HR 0.51, 95%CI 0.37-0.71, p < 0.001; PFS univariate HR 0.69, 95%CI 0.51-0.92, p = 0.013; PFS multivariate HR 0.55, 95%CI 0.41-0.75, p < 0.001). In subgroup analyses, NPC group showed trends toward better OS and PFS in both PCI < = 20 and PCI > 20 PCI score subgroups (PCI < = 20 OS: HR 0.65, 95%CI 0.42-1.01, p = 0.055; PCI > 20 OS: HR 0.71, 95%CI 0.46-1.09, p = 0.12; PCI < = 20 PFS: HR 0.69, 95%CI 0.47-1.03, p = 0.067; PCI > 20 PFS: HR 0.69, 95%CI 0.44-1.09, p = 0.11). NPC group showed significantly better PFS in both CC-0 and CC > = 1 CC-score subgroups (CC-0: HR 0.62, 95%CI 0.41-0.92, p = 0.018; CC > = 1: HR 0.49, 95%CI 0.30-0.78, p = 0.003), and trend towards better OS in CC-0 and significantly better OS in CC > = 1 subgroup (CC-0: HR 0.66, 95%CI 0.42-1.04, p = 0.074; CC > = 1: HR 0.45, 95%CI 0.29-0.70, p < 0.001). Conclusions: In this real-world data analysis of grade 2 or 3 appendiceal cancer patients undergoing CRS/HIPEC, perioperative chemotherapy was associated with worse outcomes in both univariate and multivariate analyses. These findings complement recent studies questioning the combined benefit of systemic therapy and CRS/HIPEC in this population and underscore the need for prospective trials to further investigate this question.