Prognostic Value of Circulating Tumor DNA for Recurrence and Survival in Patients Undergoing Local Treatment for Initially Unresectable RAS/RAF Mutated Colorectal Cancer Liver Metastases

BACKGROUND: Early recurrence within 6 months after surgery or ablation of initially unresectable colorectal cancer liver-only metastases (CRLM) occurs frequently and cannot be predicted by currently available clinical and pathological characteristics. This study evaluates the prognostic value of detectable circulating tumor DNA (ctDNA) before liver surgery in patients with initially unresectable CRLM.

PATIENTS AND METHODS: Patients with KRAS/NRAS/BRAF mutated tumors who underwent R0/R1 resection or ablation of all CRLM after induction systemic treatment were selected from the phase 3 CAIRO5 study. CtDNA was analyzed by droplet digital polymerase chain reaction (PCR) using blood samples collected before starting systemic treatment, before and after local liver treatment.

RESULTS: Baseline and preoperative ctDNA was analyzed in 78 patients. CtDNA was detectable at baseline in 74/78 (95%) patients and preoperatively in 18/74 (24%) patients. Preoperative ctDNA was associated with early recurrence (odds ratio [OR] 3.06, 95% CI 1.04-9.56, p = 0.046), early recurrence without salvage local treatment options (OR 4.30, 95% CI 1.43-13.72, p = 0.011), and overall survival (hazard ratio 2.19, 95% CI 1.22-3.91, p = 0.007).

DISCUSSION: Preoperative ctDNA is prognostic for early recurrence and overall survival after local liver treatment in patients with initially unresectable CRLM and KRAS/NRAS/BRAF mutated primary tumors. Further research should determine how to incorporate this parameter into clinical risk scores and therapy management.