Background/Objectives: BRAF mutations occur in 5–10% of metastatic colorectal cancer (mCRC) cases, but their implications for prognosis and optimal treatment remain unclear. Methods: This multicenter, prospective observational study analyzed 377 RAS wild-type cases from 511 patients across 32 centers, using PCR-based methods. Results: BRAF mutations were identified in 21% (79/377) of cases, predominantly V600E (89.9%) with a minority of non-V600E (10.1%). Microsatellite instability (MSI) testing revealed MSI-high in 11.3%, exclusively among V600E cases. V600E mutations were linked to right-sided tumors, poor differentiation, and elevated CA19-9 levels. Median survival was significantly lower in V600E cases compared to BRAF wild-type (12.4 vs. 37.5 months, HR 3.25,p< 0.001) and marginally lower non-V600E cases (12.4 vs. 34.7 months, HR 0.61,p= 0.057). Chemotherapy regimens (doublet vs. triplet) and targeted treatments (bevacizumab vs. anti-EGFR) showed no significant survival differences in V600E patients. Similarly, RAS/BRAF wild-type patients had comparable survival with bevacizumab versus anti-EGFR, even for left-sided tumors. Conclusions: These findings highlight distinct clinical and prognostic profiles for BRAF V600E and non-V600E mutations, while treatment choice appears to have limited impact on survival in these subgroups or RAS/BRAF wild-type cases.
**背景/目的：** BRAF突变发生于5-10%的转移性结直肠癌（mCRC）病例中，但其对预后和最佳治疗方案的影响尚不明确。 **方法：** 这项多中心、前瞻性观察性研究纳入了来自32个中心的511例患者，采用基于PCR的方法，分析了其中377例RAS野生型病例。 **结果：** 在377例病例中，21%（79/377）检测到BRAF突变，主要为V600E突变（89.9%），少数为非V600E突变（10.1%）。微卫星不稳定性（MSI）检测显示，11.3%的病例为MSI-H，且全部出现在V600E突变病例中。V600E突变与右侧原发肿瘤、低分化以及CA19-9水平升高相关。与BRAF野生型病例相比，V600E突变病例的中位生存期显著缩短（12.4个月 vs. 37.5个月，HR 3.25，p < 0.001）；非V600E突变病例的中位生存期也略低于野生型（12.4个月 vs. 34.7个月，HR 0.61，p = 0.057）。在V600E突变患者中，化疗方案（双药 vs. 三药）和靶向治疗（贝伐珠单抗 vs. 抗EGFR治疗）均未显示出显著的生存差异。同样，对于RAS/BRAF野生型患者，贝伐珠单抗与抗EGFR治疗的生存期相当，即使是左侧原发肿瘤患者也是如此。 **结论：** 这些发现突显了BRAF V600E突变与非V600E突变具有不同的临床和预后特征，而治疗选择对这些亚组或RAS/BRAF野生型病例的生存期影响似乎有限。
肿瘤(癌症)患者之家