Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A pragmatic comparison of oncological outcomes in synchronous versus metachronous disease

Background: disease burden (PCI), completeness of cytoreduction or histological features, are known to influence survival after CRS-HIPEC for colorectal peritoneal metastases (CPM). However, there is still debate about influence of CPM onset. The aim of this study is to determine the impact of CPM onset on oncological outcomes after CRS-HIPEC. Methods: all patients with CPM scheduled for CRS-HIPEC at one reference center between December 2007 and September 2022 were included. s-PM were defined as those diagnosed at primary disease treatment; m-PM were considered those diagnosed during follow-up. Survival outcomes and recurrence rates were compared using a pragmatic analysis. Results: 125 patients with s-CPM and 170 patients with m-CPM were analyzed. Median follow-up was 58.6 and 50.6 months in s-CPM and m-CPM groups(p = 0.11). Complete cytoreduction (CCS-0/-1) rates were comparable: 84 % s-CPM vs. 88.2 % m-CPM(p = 0.190). Overall survival (OS) was significantly shorter in s-CPM: 24.7 vs. 46.6 months (p = 0.024). Conversely, median disease-free survival was similar in both groups, 10 months vs. 11 months(p = 0.155). Patients in the s-CPM group presented more pN+(p = 0.001), higher histologic grade(p = 0.007) and PCI(p = 0.04), and higher rate of concurrent liver metastases(p = 0.004). RAS/BRAF gene mutations and microsatellite instability did not differ significantly. Perioperative chemotherapy regimens and tolerance were also similar. Conclusions: despite s-CPM being associated with impaired OS after CRS-HIPEC, the onset of PM was not found to be an independent determinant for survival. High-risk molecular and histological features strongly influence oncological outcomes after CRS-HIPEC. This is valuable data that could aid in preoperative patient selection process for CRS-HIPEC.