Pre-operative chemotherapy response and survival in patients with colorectal cancer peritoneal metastases

International guidelines (ASCO, ESMO) informed by PRODIGE-7 recommend peri-operative systemic chemotherapy before cytoreductive surgery (CRS) for colorectal cancer peritoneal metastases (CRPM). Chemotherapy response and impact on survival has not been reported. Toxicity profiles associated with multi-modal treatment need to be better defined.
We assessed CRPM patients who received systemic chemotherapy with oxaliplatin or irinotecan before CRS (pre-operative) and Mitomycin C/Oxaliplatin heated intraperitoneal chemotherapy (HIPEC). Secondary analysis was performed from a prospective database. Overall survival (OS) in chemotherapy responders (R) and non-responders (NR) was compared. Toxicity was assessed by rate of adverse events (AEs).
From April 2005-April 2021, 436 patients underwent CRS+HIPEC; 125 (29%) received pre-CRS chemotherapy. 112 (90%) received first line oxaliplatin (64, 57%) or irinotecan (48, 43%). R, defined as complete (CR) or partial response (PR) on pre-operative imaging and/or post-operative histology, was seen in 71, 63% (62.9-63.1) prior to CRS ; 16, 14% (13.9-14.1) had CR. NR included stable/progressive disease. Median OS in R vs NR was 43.7 months (37.9-49.4) vs 23.9 (16.3-31.4) p=0.007, HR 0.51 (0.31-0.84). OS multivariable analysis showed HR 0.48 (0.25-0.95), p=0.03 for chemotherapy response corrected by peritoneal cancer index and completeness of cytoreduction score. CRS was associated with 21% grade 3-4 AEs versus 4% for pre-operative chemotherapy. HIPEC grade 3-4 AEs were 0.5%.
Pre-operative chemotherapy response is an independent predictor for OS in CRPM. This is the first study to report chemotherapy response before CRS+HIPEC in CRPM. HIPEC appears to be well tolerated.