BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases.

BACKGROUND: BRAF mutation is associated with a poor prognosis in patients with metastatic colorectal cancer. For patients with resectable colorectal liver metastases (CRLMs), the prognostic impact of BRAF mutation is unknown and the benefit of surgery debated. This nationwide intergroup (ACHBT, FRENCH, AGEO) study aimed to evaluate the oncological outcome of patients undergoing liver resection for BRAF-mutated CRLMs. METHODS: The study included patients who underwent resection for BRAF-mutated CRLMs in 24 centres between 2012 and 2016. A case-matched comparison was made with 183 patients who underwent resection of CRLMs with wild-type BRAF during the same interval. RESULTS: Sixty-six patients who underwent resection for BRAF-mutated CRLMs in 24 centres were compared with 183 patients with wild-type BRAF. The 1- and 3-year disease-free survival (DFS) rates were 46 and 19 per cent for the BRAF-mutated group, and 55·4 and 27·8 per cent for the group with wild-type BRAF (P = 0·430). In multivariable analysis, BRAF mutation was not associated with worse DFS (hazard ratio 1·16, 95 per cent c.i. 0·72 to 1·85; P = 0·547). The 1- and 3-year overall survival rates after surgery were 94 and 54 per cent respectively among patients with BRAF mutation, and 95·8 and 82·9 per cent in those with wild-type BRAF (P = 0·004). Median survival after disease progression was 23·0 (95 per cent c.i. 11·0 to 35·0) months among patients with mutated BRAF and 44·3 (35·9 to 52·6) months in those with wild-type BRAF (P = 0·050). Multisite disease progression was more common in the BRAF-mutated group (48 versus 29·8 per cent; P = 0·034). CONCLUSION: These results support surgical treatment for resectable BRAF-mutated CRLM, as BRAF mutation by itself does not increase the risk of relapse after resection. BRAF mutation is associated with worse survival in patients whose disease relapses after resection of CRLM, as for non-metastatic colorectal cancer.

Impact of the strategy for curative treatment of synchronous colorectal cancer liver metastases.

AIM OF THE STUDY: Fourteen to seventeen percent of patients suffering from colorectal cancer have synchronous liver metastases (sCRLM) at the time of diagnosis. There are currently three possible strategies for curative management of sCRLM: "classic", "combined", and "liver-first". The aim of our research was to analyze the effects of the three surgical management strategies for sCRLM on postoperative morbidity and mortality and overall and recurrence-free survival. PATIENTS AND METHODS: Patients treated for sCRLM between October 2000 and May 2015 were included. We defined three groups: (1) "classic": surgery of primary tumor and then surgery of sCRLM; (2) "combined": combined surgery of primary tumor and sCRLM: and (3) "liver-first": surgery of sCRLM and then surgery of primary tumor. RESULTS: During this period, 170 patients who underwent 209 hepatectomies were included ("classic": 149, "combined": 34, "liver-first": 26). The rate of severe complications was higher in the "combined" group compared to the "classic" group (35% vs. 12%, P=0.03), and the "liver-first" group (35% vs. 19%, P=0.25), while there were significantly fewer liver resections. Overall survival at 5 years in our cohort was 46%, without significant differences between the groups, and a median survival of 54 months. Recurrence-free survival of the patients in our cohort was 24% at 5 years, with a median survival time without recurrence of 14 months, without significant differences between the groups. CONCLUSION: All three strategies were feasible and there were no differences regarding overall and recurrence-free survivals between the three approaches. The "combined" strategy group had significantly more severe complications and did not provide better oncological results, despite less aggressive liver disease and more limited liver resections.