Preoperative detection of KRAS mutated circulating tumor DNA is an independent risk factor for recurrence in colorectal cancer

Abstract

Preoperative ctDNA status in relation to recurrence in cases of CRC remains unclear. We examined preoperative ctDNA detection by targeting KRAS gene mutations as a predictive marker for recurrence after CRC surgery. We measured the preoperative KRAS mutated ctDNA status and analyzed the correlation with clinicopathologic features of 180 patients that underwent surgery for CRC. We studied the association between preoperative KRAS mutated ctDNA and postoperative recurrence in patients (n = 150) that underwent radical surgery. KRAS mutated ctDNA was detected in 59 patients (32.8%). Median mutant allele frequency of KRAS in ctDNA was 0.20%. KRAS status in ctDNA and lymph node metastasis and distant metastasis were not significantly different. Among patients that underwent radical resection, recurrence occurred in 21 (14.0%, median follow-up 24 months). In Kaplan–Meier analysis, preoperative detection of KRAS mutated ctDNA was associated with inferior recurrence-free interval (RFI) (p = 0.002) and recurrence-free survival (RFS) (p = 0.025). In a multivariate Cox proportional hazards model, preoperative detection of KRAS mutated ctDNA was an independent factor related to both RFI (HR = 3.08; p = 0.012) and RFS (HR = 2.18; p = 0.044). Preoperative measurement of KRAS mutated ctDNA could be useful to decide postoperative treatment.