Optimal duration of neoadjuvant chemotherapy prior to CRS±HIPEC for colorectal cancer: An assessment of survival and postoperative outcomes.
Authors: Frances Jenkins Bennett, Kailey Morgan Oppat, Mohammad Yahya Zaidi, Joshua Winer, Maria C. Russell, Charles A. Staley, Shishir K. Maithel, Seth Jason Concors
Journal: Journal of Clinical Oncology (2025)

188 Background: Cytoreductive surgery (CRS) with or without heated intraperitoneal chemotherapy (HIPEC) represents a viable treatment option for select patients with colorectal cancer peritoneal metastases. Given high recurrence rates after surgery, it is common practice to administer neoadjuvant chemotherapy (NAC). The optimal duration, however, when considering oncologic value and postoperative outcomes, is not known. Methods: A single institution database (2009-2024) of colorectal cancer patients that underwent CRS±HIPEC was reviewed. Patients with colorectal cancer undergoing CRS±HIPEC for curative intent (completeness of cytoreduction 0 or 1) with known NAC duration were included. Analysis was stratified by NAC duration of 0-3 months or greater than 3 months. Co-primary outcomes were recurrence free survival (RFS) and overall survival (OS). Secondary outcomes included clinically significant complications, defined as Grade 3 or greater adverse events based on Common Terminology Criteria for Adverse Events Version 5.0. Results: From 2009-2024, 108 patients underwent CRS±HIPEC for colorectal cancer. Final analysis included 84 patients that underwent curative intent surgery and had a known duration of NAC ( &gt; 3 months NAC: 55 patients, 0-3 months NAC: 29 patients). Median peritoneal cancer index (PCI) score was similar between the two cohorts ( &gt; 3 months: median PCI 11 versus (vs) 0-3 months: median PCI 12; p = 0.42). Recurrence-free survival was 9 months for the entire cohort and not significantly different based on duration of NAC ( &gt; 3 months: 8 months vs 0-3 months: 15 months, p = 0.14). Overall survival was also similar between both cohorts ( &gt; 3 months: 26 months vs 0-3 months: 37 months; p = 0.11). On univariate analysis, &gt; 3 months of NAC was associated with an increased rate of complications of any severity ( &gt; 3 months: 83.6% vs 0-3 months: 55.2%; p = 0.01), clinically significant complications ( &gt; 3 months: 54.5% vs 0-3 months: 31.0%; p = 0.07), and increased median length of stay ( &gt; 3 months: 10 days vs 0-3 months: 8 days; p = 0.01). When controlling for other perioperative variables on multivariable analysis, &gt; 3 months of NAC trended towards an increased risk of clinically significant complications (HR 1.76, 95% CI 0.59-5.30; p = 0.32). Conclusions: Even with a similar disease burden, as measured by PCI, an extended duration of neoadjuvant chemotherapy prior to CRS±HIPEC does not appear to be associated with any improved recurrence-free or overall survival. Conversely, postoperative outcomes are worse with higher complication rates and increased length of stay. Thus, despite high recurrence rates after CRS±HIPEC for this disease, it still appears that in well selected patients, an extended duration of neoadjuvant chemotherapy may not be the best treatment strategy.