Outcomes and Molecular Correlates of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases

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BACKGROUND: Colorectal peritoneal metastases occur in approximately 13% of colorectal cancer cases. median survival with systemic chemotherapy alone is 10 to 18 months. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy can extend survival to approximately 41 months, but judicious patient selection is crucial. OBJECTIVE: To describe outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases patients according to tumor mutational profile (variants BRAF V600E, KRAS G12V and KRAS G12D). DESIGN: A retrospective cohort analysis of colorectal peritoneal metastases patients who underwent this procedure between 2012 and 2024. SETTINGS: The study was conducted at Peter MacCallum Cancer Centre, the state-wide peritoneal malignancy center for Victoria and Tasmania, Australia. PATIENTS: A total of 256 patients were included, and iterative procedures were excluded. MAIN OUTCOME MEASURES: Overall survival and disease-free survival according to molecular stratification were the primary outcomes. Secondary outcomes included length of stay, 90-day morbidity and mortality. RESULTS: The median peritoneal cancer index score was 9 (range, 0 to 39). Median overall survival and disease-free survival for patients with complete cytoreductive clearance (204/256) was 43 and 10 months, respectively. KRAS G12V variant was associated with inferior overall survival relative to the RAS/RAF-wildtype group (median 34 months, p = 0.04). BRAF V600E was associated with inferior disease-free survival relative to the RAS/RAF-wildtype group (median 9 months, p = 0.02). KRAS G12V mutation (p = 0.008) was an independent prognostic factor for poorer overall survival, and BRAF V600E (p = 0.01) was an independent prognostic factor for worse disease-free survival on multivariate analysis. Overall, anastomotic leak occurred in 3.9%, return to theater in 6.3%, and perioperative mortality in 1.2%. LIMITATIONS: This study is limited by its retrospective design and single-center setting. CONCLUSIONS: BRAF V600E and KRAS G12V mutations confer poorer disease outcomes in these patients. KRAS G12D mutation appears prognostically neutral. Molecular features alongside clinical and pathological factors should guide patient selection to optimize outcomes. See Video Abstract.

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