Survival Outcomes of Patients with BRAF V600E-Mutant Resectable Extrahepatic Colorectal Oligometastases After Upfront...

The negative impact of the BRAF V600E mutation (mBRAF) on survival outcomes has been reported for metastatic colorectal cancer (mCRC), but the role of mBRAF testing in resectable extrahepatic cases remains unclear. This study aimed to assess survival outcomes in patients with extrahepatic mCRC harboring mBRAF who underwent upfront metastasectomy, compared with patients with unresectable mBRAF tumors.

A single-center retrospective study was conducted between January 2005 and December 2017. Of 109 patients who underwent initial metastasectomy for extrahepatic mCRC without preoperative chemotherapy, mBRAF, RAS mutations (mRAS), and wild-type RAS/BRAF (wtRAS/BRAF) were found in 6 (5.5%), 64 (58.7%), and 39 (35.8%) patients, respectively.

After a median follow-up of 39.5 months, patients with mBRAF had a median recurrence-free survival (RFS) of 4.4 months and overall survival (OS) of 40.6 months. In multivariate survival analysis, mBRAF status was the strongest independent predictor of poor survival, even after adjusting for conventional clinicopathological factors and other mutational statuses (RFS: HR 3.15, p = 0.035; OS: HR 3.85, p = 0.037). The OS after upfront metastasectomy in mBRAF cases was nearly identical to that of unresectable mCRC treated with systemic chemotherapy (HR 1.01, p = 0.99).

Technically resectable extrahepatic oligometastases with mBRAF may be considered oncologically unresectable. Preoperative mBRAF testing should be considered for all patients with resectable extrahepatic mCRC, regardless of technical resectability.