Perioperative Circulating Tumor DNA Dynamics in Patients Undergoing Cytoreductive Surgery for Colorectal Peritoneal Metastases

Abstract Background Circulating tumor DNA (ctDNA) is a strong prognostic biomarker in resectable colorectal cancer but remains poorly studied in patients with colorectal peritoneal metastases (CRPM). This study aims to report perioperative ctDNA dynamics in patients undergoing cytoreductive surgery (CRS) for CRPM and evaluate whether pre- and postoperative ctDNA detection was associated with recurrence and survival. Methods Patients who underwent CRS for CRPM at a single center between 2021 and 2025 and had one or more perioperative ctDNA result available were included. Clinicopathological, recurrence, and survival data were retrospectively collected from electronic medical records. ctDNA results were extracted from a prospectively maintained institutional database. Results In total, 87 patients were included, with a median follow-up of 26.2 months. Pre-neoadjuvant therapy, post-neoadjuvant/pre-CRS, and post-CRS ctDNA was detectable in 65% (22 of 34), 27% (10 of 37), and 36% (30 of 83) of patients, respectively. Post-neoadjuvant/pre-CRS ctDNA positivity was associated with shorter recurrence-free survival (RFS; hazard ratio [HR] 2.59; 95% confidence interval [CI] 1.06–6.34, p =0.037) and overall survival (HR 5.73; 95% CI 0.92–35.5, p =0.061). Post-CRS ctDNA positivity was associated with shorter RFS (HR 3.5; 95% CI 2.1–5.9, p <0.001), peritoneal RFS (HR 3.1; 95% CI 1.7–5.5, p <0.001), and overall survival (HR 6.7; 95% CI 2.3–19.7, p =0.001). Conclusions A smaller proportion of patients with CRPM have detectable ctDNA at presentation compared with other anatomic sites. However, post-CRS ctDNA positivity is strongly associated with recurrence and poorer survival, and dynamic perioperative ctDNA changes may be prognostically informative. ctDNA response to neoadjuvant treatment may demonstrate favorable tumor biology and response to treatment.