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Colorectal

P9: Impact of KRAS Mutation on Recurrence-Free Survival in Colorectal Cancer Patients Undergoing HIPEC

Introduction: Colorectal cancer (CRC) is a molecularly heterogeneous disease with KRAS mutations generally associated with a worse prognosis and decreased survival. Although still controversial, the role of cytoreductive surgery (CRS) with the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced stage CRC may proffer some survival benefit. Few studies have described the post-operative morbidity and mortality among mutKRAS and wildtype patients undergoing CRS/HIPEC for advanced CRC.

Methods: Using a prospective cohort of 276 patients undergoing CRS/HIPEC, we identified 92 patients with CRC. Patients were categorized based on the presence (mutKRAS) or absence (wildtype) of KRAS mutations. Patient characteristics, tumor factors, treatment, and clinical outcomes were compared between groups. Post-operative morbidity was measured by Clavian-Dindo Classification (CDC). Kaplan-Meier survival analysis evaluated recurrence-free survival (RFS) between groups.

Results: Of the 92 patients, 45 (48.9%) were identified with a KRAS mutation. Median age for wildtype was 52 (44-62) years and 50 (43-61) year for mutKRAS. Patient and tumor characteristics were similar among groups. Most of the cohort (85.6%, n=83) presented with Stage 3 or 4 disease. While the wildtype had higher rates of metastasis than mutKRAS (83.0% vs 64.4%, respectively; p=0.046), the mutKRAS group had less patients achieve an R0 resection and higher rates of post-operative complications. While not statistically significant, median PCI at exploration for mutKRAS patients, 13 (5-24), was higher than wildtype, [8 (5-15), p=0.05]. Median follow up time for the cohort was 45.8 mos, 41.4 mos for wildtype, and 48.7 mos for mutKRAS. There was no significant difference in RFS between groups (p=0.73).

Conclusions: Contrary to the typical association of KRAS mutations with poorer survival in CRC, our findings suggest that patients with this mutation have comparable RFS to those without when treated with CRS/HIPEC. This may imply that CRS/HIPEC offers therapeutic benefits for KRAS-mutant CRC patients, potentially mitigating the usually adverse prognosis associated with this mutation.

Learning Objectives:

  • Appreciate the complexities surrounding the utilization of cytoreductive surgery (CRS) in conjunction with hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced stage CRC.
  • Describe the molecular heterogeneity in colorectal cancer (CRC) and its implications on patient prognosis, with a specific focus on the role of KRAS mutations.
  • Understand differences in patient, tumor, and treatment factors in patients with and without a KRAS mutation undergoing CRS/HIPEC.