BRAF V600E potentially determines "Oncological Resectability" for "Technically Resectable" colorectal liver metastases

Despite reports on poor survival outcomes after hepatectomy for colorectal liver metastases (CRLM) with BRAF V600E mutation (mBRAF) exist, the role of mBRAF testing for technically resectable cases remains unclear. A single-center retrospective study was performed to investigate the survival outcomes of patients who underwent upfront hepatectomy for solitary resectable CRLM with mBRAF between January 2005 and December 2017 and to compare them with those of unresectable cases with mBRAF. Of 172 patients who underwent initial hepatectomy for solitary resectable CRLM, mBRAF, RAS mutations (mRAS), and wild-type RAS/BRAF (wtRAS/BRAF) were observed in 5 (2.9%), 73 (42.4%), and 93 (54.7%) patients, respectively. With a median follow-up period of 72.8 months, mBRAF was associated with a significantly shorter OS (median, 14.4 months) than wtRAS/BRAF (median, not reached [NR]) (hazard ratio [HR], 27.6; p < 0.001) and mRAS (median, NR) (HR, 9.9; p < 0.001), and mBRAF had the highest HR among all the indicators in the multivariable analysis (HR, 17.0; p < 0.001). The median OS after upfront hepatectomy for CRLM with mBRAF was identical to that of 28 unresectable CRLM with mBRAF that were treated with systemic chemotherapy (median, 17.2 months) (HR, 0.78; p = 0.65). When technically resectable CRLM are complicated with mBRAF, its survival outcome becomes as poor as unresectable cases; therefore, those with mBRAF should be considered as oncologically unresectable. Patients with CRLM should undergo pre-treatment mBRAF testing regardless of technical resectability.