Running head of title: Systemic anticancer & intraperitoneal

Cytoreductive surgery (CRS) is effective for colorectal cancer peritoneal metastases (CRPM) at increasing overall survival (OS) compared to systemic anti-cancer treatment (SACT) alone. The addition of Oxaliplatin heated intraperitoneal chemotherapy (HIPEC) has been shown in a randomised controlled trial to result in increased complications without significant OS benefit. This study evaluates outcomes for CRPM patients undergoing CRS+HIPEC with Oxaliplatin (Ox) 368mg/m²(30 min), versus Mitomycin C (MMC) 35mg/m² (90min). <br/>A prospective CRPM real-world database was used to collect outcomes for patients undergoing CRS+HIPEC at a single centre. OS, recurrence-free (RFS), peritoneal RFS (PeRFS) were compared amongst all patients with histologically proven CRPM, those with completeness of cytoreduction (CC) score =0/1, and those with CC score=0/1 who were SACT naïve. <br/>Between April 2005-April 2021, 409 patients underwent CRS+HIPEC: 271 (66%) had MMC, 138 (34%) Ox. Of these, 395 (97%) had histologically confirmed CRPM, 336 (85%) achieved CC=0/1, 188 (47%) were SACT naïve; median OS =39.5, 44.4, and 47.2 months respectively. MMC vs Ox median OS in CC0/1=43.7 (95% CI 35.9-48.3) vs 50.1 (39.7-70.2) months, p=0.28; Median OS in SACT naïve=45.7 (39.4-65.9) vs 59.9 (38.3-82.0) months, p=0.31; multivariable analysis for CC0/1, SACT naïve patients showed Ox was comparable to MMC: HR=0.90, (0.64-1.27) p=0.55 vs HR=0.88, (0.53-1.44) p=0.60, respectively. Ox resulted in a significantly improved PeRFS in CC0/1 patients (MMC=9.0 vs Ox=12.6months, p=0.01). A multivariable model for PeRFS showed a HR=0.63, (0.43-0.95), p=0.03 for Ox. <br/>This study suggests a role for Ox HIPEC in CRPM which should be explored further in clinical trials.<br/>