Mori Takashi, Kobayashi Shin, Tsukada Yuichiro, Kojima Motohiro, Kitaguchi Daichi, Hasegawa Hiro, Ikeda Koji, Nishizawa Yuji, Gotohda Naoto, Bando Hideaki, Tsuboi Masahiro, Ito Masaaki, Yoshino Takayuki
Department of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-Ward, Tokyo, 113-8421, Japan.
J Gastrointest Cancer. 2025 Sep 22;56(1):192. doi: 10.1007/s12029-025-01315-8.
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.
已有报道称BRAF V600E突变（mBRAF）对转移性结直肠癌（mCRC）的生存结局有负面影响，但mBRAF检测在可切除的肝外病例中的作用仍不明确。本研究旨在评估接受 upfront 肝外转移灶切除术的携带mBRAF的肝外mCRC患者与不可切除的mBRAF肿瘤患者的生存结局。
2005年1月至2017年12月进行了一项单中心回顾性研究。在109例未接受术前化疗的肝外mCRC初次肝外转移灶切除患者中，分别有6例（5.5%）、64例（58.7%）和39例（35.8%）患者检测到mBRAF、RAS突变（mRAS）和野生型RAS/BRAF（wtRAS/BRAF）。
中位随访39.5个月后，mBRAF患者的无复发生存期（RFS）中位数为4.4个月，总生存期（OS）为40.6个月。在多因素生存分析中，即使在调整了传统临床病理因素和其他突变状态后，mBRAF状态仍是生存不良的最强独立预测因素（RFS：风险比[HR] 3.15，p = 0.035；OS：HR 3.85，p = 0.037）。mBRAF病例 upfront 肝外转移灶切除术后的OS与接受全身化疗的不可切除mCRC患者的OS几乎相同（HR 1.01，p = 0.99）。
技术上可切除的携带mBRAF的肝外寡转移灶在肿瘤学上可能被视为不可切除。对于所有可切除的肝外mCRC患者，无论技术上是否可切除，均应考虑进行术前mBRAF检测。
