The indications for adjuvant vascular endothelial growth factor–tyrosine kinase inhibitor (VEGF-TKI) agents after curative intent nephrectomy for renal cell carcinoma are still a matter of debate. The ASSURE, PROTECT and ATLAS trials have failed to meet their primary end-points. Conversely, S-TRAC has shown a disease free survival (DFS) benefit. To date, meta-analyses have repeatedly proved the absence of a clinical benefit, in term of DFS and overall survival (OS). Nevertheless, the results of the SORCE trial have been recently released and might add valuable information. We pooled the results of all five reported trials testing for any potential DFS and OS benefits associated with VEGF-TKI use. Interestingly, for pooled DFS we found a marginal positive hazard ratio (HR) of 0.92 (95% confidence interval [CI] 0.85-1.00; P-value = 0.049) in favor of adjuvant VEGF-TKI agents. This benefit was more pronounced for DFS in the sub-groups of only high-risk patients (HR: 0.89, 95% CI 0.80-0.99; P-value = 0.026), but less pronounced in clear-cell only subgroup (HR 0.92, 95% CI: 0.85-1.00; P-value = 0.044). Overall survival benefit was instead not reached. However, pooled relative risk for high-grade (grade ≥3 according to CTCAE classification) adverse events was irremediably high, 2.56 (95% CI: 2.15-3.04; P-value < 0.001). Given the marginal benefit in terms of DFS and the drawback of high-grade adverse events, even after the SORCE trial publication, adjuvant VEGF-TKIs therapy cannot be considered in the whole group of patients with non-metastatic high-risk renal cell carcinoma after surgery.

肾细胞癌根治性肾切除术后辅助血管内皮生长因子-酪氨酸激酶抑制剂 (VEGF-TKI) 药物的适应症仍存在争议。ASSURE、PROTECT 和 ATLAS 试验未能达到其主要终点。相反，S-TRAC 已显示出无病生存 (DFS) 益处。迄今为止，荟萃分析一再证明在 DFS 和总生存期 (OS) 方面没有临床益处。尽管如此，SORCE 试验的结果最近已经发布，可能会增加有价值的信息。我们汇总了所有五项报告试验的结果，测试与使用 VEGF-TKI 相关的任何潜在的 DFS 和 OS 益处。有趣的是，对于合并 DFS，我们发现边际阳性风险比 (HR) 为 0.92（95% 置信区间 [CI] 0.85-1.00；P-值 = 0.049) 支持 VEGF-TKI 辅助药物。这种益处在仅高危患者亚组中对 DFS 更为明显（HR：0.89，95% CI 0.80-0.99；P值 = 0.026），但在仅透明细胞亚组中不太明显（HR 0.92， 95% CI：0.85-1.00；P值 = 0.044)。相反，没有达到总体生存获益。然而，高级别（根据 CTCAE 分类≥3 级）不良事件的汇总相对风险非常高，为 2.56（95% CI：2.15-3.04；P-值 < 0.001)。鉴于 DFS 的边际收益和高级别不良事件的缺点，即使在 SORCE 试验发表后，也不能在非转移性高危肾细胞癌患者的整个组中考虑辅助 VEGF-TKI 治疗。手术。