Aims: RAS/BRAF mutational status plays a prognostic and predictive role in metastatic colorectal cancer. Therefore, stratification of patients with colorectal peritoneal metastases (CRPM) using these biomarkers may refine patient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This study aimed to analyse the association of RAS/BRAF status with clinicopathological variables and survival outcomes in patients who have undergone CRS and HIPEC.
Methods: A single centre, prospectively maintained peritonectomy database was interrogated for patients with CRPM who underwent peritonectomy procedures between 2009 and 2020. Differences between clinicopathological variables and RAS/BRAF status were tested for statistical independence. Survival analysis was performed using Kaplan-Meier estimation, with differences evaluated by log-rank test.
Results: One hundred and seventy-three patients underwent peritonectomy procedures during the study period. RAS status was obtained on 125 patients, with 52 (41.6%) KRAS mutants detected. BRAF status was assessed in 111 patients, 14 (12.6%) of which had a BRAF mutation. The most common BRAF and KRAS variants were, V600E (78.5%) and G12D (35.3%), respectively. There was no significant difference in peritoneal carcinomatosis index (p=0.534), completeness of cytoreduction (p=0.697) and presence of mucinous (p=0.062) or signet ring cell (p=0.353) histology between either mutant and wild type patients. As expected, BRAF mutant patients were more likely to be mismatch repair deficient (p=0.044). There was no difference in overall survival between patients with KRAS (p=0.866) and BRAF (p=0.760) mutant tumours and their wild type counterparts. However, both KRAS and BRAF mutant patients experienced significantly inferior disease-free survival (KRAS: median 10 vs 13 months, p=0.049; BRAF: median 8 vs 13 months, p=0.034).
Conclusion: RAS/BRAF mutations are associated with inferior disease-free survival post CRS and HIPEC and may refine patient selection for this procedure. Molecular analysis should be routinely performed on these patients preoperatively to stratify prognosis and guide neoadjuvant or adjuvant targeted therapy.