Department of Oncology and Radiotherapeutics, Faculty of Medicine, University Hospital in Pilsen, Charles University Prague, Alej Svobody 80, 304 60, Pilsen, Czech Republic.
Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 76, Pilsen, Czech Republic.
Target Oncol. 2024 Jul;19(4):587-599. doi: 10.1007/s11523-024-01065-w. Epub 2024 May 5.
BACKGROUND: About 20% of patients with renal cell carcinoma present with non-clear cell histology (nccRCC), encompassing various histological types. While surgery remains pivotal for localized-stage nccRCC, the role of cytoreductive nephrectomy (CN) in metastatic nccRCC is contentious. Limited data exist on the role of CN in metastatic nccRCC under current standard of care. OBJECTIVE: This retrospective study focused on the impact of upfront CN on metastatic nccRCC outcomes with first-line immune checkpoint inhibitor (IO) combinations or tyrosine kinase inhibitor (TKI) monotherapy. METHODS: The study included 221 patients with nccRCC and synchronous metastatic disease, treated with IO combinations or TKI monotherapy in the first line. Baseline clinical characteristics, systemic therapy, and treatment outcomes were analyzed. The primary objective was to assess clinical outcomes, including progression-free survival (PFS) and overall survival (OS). Statistical analysis involved the Fisher exact test, Pearson's correlation coefficient, analysis of variance, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. RESULTS: Median OS for patients undergoing upfront CN was 36.8 (95% confidence interval [CI] 24.9-71.3) versus 20.8 (95% CI 12.6-24.8) months for those without CN (p = 0.005). Upfront CN was significantly associated with OS in the multivariate Cox regression analysis (hazard ratio 0.47 [95% CI 0.31-0.72], p < 0.001). In patients without CN, the median OS and PFS was 24.5 (95% CI 18.1-40.5) and 13.0 months (95% CI 6.6-23.5) for patients treated with IO+TKI versus 7.5 (95% CI 4.3-22.4) and 4.9 months (95% CI 3.0-8.1) for those receiving the IO+IO combination (p = 0.059 and p = 0.032, respectively). CONCLUSIONS: Our study demonstrates the survival benefits of upfront CN compared with systemic therapy without CN. The study suggests that the use of IO+TKI combination or, eventually, TKI monotherapy might be a better choice than IO+IO combination for patients who are not candidates for CN regardless of IO eligibility. Prospective trials are needed to validate these findings and refine the role of CN in current mRCC management.
背景：约 20%的肾细胞癌患者呈现非透明细胞组织学（nccRCC），包括各种组织学类型。虽然手术仍然是局限性 nccRCC 的关键治疗方法，但细胞减积性肾切除术（CN）在转移性 nccRCC 中的作用存在争议。在当前的标准治疗下，关于 CN 在转移性 nccRCC 中的作用的数据有限。
目的：本回顾性研究重点关注一线免疫检查点抑制剂（IO）联合或酪氨酸激酶抑制剂（TKI）单药治疗时， upfront CN 对转移性 nccRCC 结局的影响。
方法：该研究纳入了 221 例 nccRCC 伴同步转移性疾病患者，一线接受 IO 联合或 TKI 单药治疗。分析了基线临床特征、系统治疗和治疗结局。主要研究目的是评估临床结局，包括无进展生存期（PFS）和总生存期（OS）。统计分析采用 Fisher 确切检验、Pearson 相关系数、方差分析、Kaplan-Meier 法、对数秩检验和单变量/多变量 Cox 比例风险回归模型。
结果： upfront CN 组的中位 OS 为 36.8（95%置信区间 [CI] 24.9-71.3），而无 CN 组为 20.8（95% CI 12.6-24.8）（p=0.005）。多变量 Cox 回归分析显示 upfront CN 与 OS 显著相关（风险比 0.47 [95% CI 0.31-0.72]，p<0.001）。在无 CN 的患者中，IO+TKI 治疗组的中位 OS 和 PFS 分别为 24.5（95% CI 18.1-40.5）和 13.0 个月（95% CI 6.6-23.5），IO+IO 联合治疗组分别为 7.5（95% CI 4.3-22.4）和 4.9 个月（95% CI 3.0-8.1）（p=0.059 和 p=0.032）。
结论：本研究表明 upfront CN 与无 CN 的系统治疗相比具有生存获益。研究表明，对于不适合 CN 的患者，IO+TKI 联合治疗或最终 TKI 单药治疗可能优于 IO+IO 联合治疗。需要前瞻性试验来验证这些发现，并完善 CN 在当前 mRCC 管理中的作用。
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