Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Eur Urol Focus. 2023 Sep;9(5):734-741. doi: 10.1016/j.euf.2023.02.008. Epub 2023 Feb 28.
Renal cell carcinoma (RCC) with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is a highly aggressive tumor with a poor prognosis. Immune checkpoint therapy (ICT) has shown significant treatment efficacy in this subtype. There remains uncertainly regarding the role of cytoreductive nephrectomy (CN) for patients with metastatic RCC (mRCC) with S/R who received ICT.
Here, we report the outcomes with ICT for patients with mRCC and S/R dedifferentiation by CN status.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was conducted of 157 patients with sarcomatoid, rhabdoid, or sarcomatoid plus rhabdoid dedifferentiation who received an ICT-based regimen at two cancer centers.
CN performed at any time point; nephrectomy with curative intent was excluded.
ICT treatment duration (TD) and overall survival (OS) from ICT initiation were recorded. To address the immortal time bias, a time-dependent Cox regression model was generated that accounted for confounders identified by a directed acyclic graph as well as a time-dependent nephrectomy variable.
A total of 118 patients underwent CN, and of them, 89 underwent upfront CN. The results did not contradict the supposition that CN does not improve ICT TD (hazard ratio [HR] 0.98, 95% confidence interval [CI] 0.65-1.47, p = 0.94) or OS from ICT initiation (HR 0.79, 95% CI 0.47-1.33, p = 0.37). In patients who underwent upfront CN compared with those who did not undergo CN, there was no association with ICT duration or OS (HR 0.61, 95% CI 0.35-1.06, p = 0.08). A detailed clinical summary of 49 patients with mRCC and rhabdoid dedifferentiation is provided.
In this multi-institutional cohort of mRCC with S/R dedifferentiation treated with ICT, CN was not significantly associated with improved TD or superior OS when accounting for the lead time bias. There appears to be a subset of patients who derive meaningful benefit from CN, so improved tools for stratification prior to CN are needed to optimize outcomes.
Immunotherapy has improved outcomes for patients with metastatic renal cell carcinoma (mRCC) who have sarcomatoid and/or rhabdoid (S/R) dedifferentiation, which is an aggressive and uncommon feature; yet, the utility of a nephrectomy in this setting is unclear. We found that nephrectomy did not significantly improve survival or time on immunotherapy for these patients with mRCC and S/R dedifferentiation; yet, there may be a subset of patients who benefit from this surgical approach.
具有肉瘤样和/或横纹肌样去分化（S/R）的肾细胞癌（RCC）是一种侵袭性强、预后差的肿瘤。免疫检查点治疗（ICT）在这种亚型中显示出显著的治疗效果。对于接受 ICT 的转移性肾细胞癌（mRCC）伴 S/R 的患者，是否进行减瘤性肾切除术（CN）仍然存在不确定性。
本研究报告了根据 CN 状态对 mRCC 伴 S/R 去分化患者进行 ICT 的结果。
设计、地点和参与者：对在两个癌症中心接受基于 ICT 的治疗方案的 157 名具有肉瘤样、横纹肌样或肉瘤样加横纹肌样去分化的患者进行了回顾性研究。
任何时间点进行 CN；排除根治性肾切除术。
记录 ICT 治疗持续时间（TD）和 ICT 开始后的总生存期（OS）。为了解决不朽时间偏差，生成了一个时间依赖性 Cox 回归模型，该模型考虑了由有向无环图确定的混杂因素以及时间依赖性肾切除术变量。
共有 118 名患者接受了 CN，其中 89 名患者接受了 upfront CN。结果并未反驳 CN 不会改善 ICT TD（风险比[HR]0.98，95%置信区间[CI]0.65-1.47，p=0.94）或 ICT 开始后的 OS（HR 0.79，95% CI 0.47-1.33，p=0.37）的假设。与未接受 CN 的患者相比， upfront CN 的患者与 ICT 持续时间或 OS 无关（HR 0.61，95% CI 0.35-1.06，p=0.08）。提供了 49 名 mRCC 伴横纹肌样去分化患者的详细临床总结。
在本项多中心研究中，对接受 ICT 治疗的 mRCC 伴 S/R 去分化患者进行了分析，在考虑到领先时间偏差的情况下，CN 与 ICT TD 或 OS 的改善无关。似乎有一部分患者从 CN 中获得了显著的益处，因此需要改进术前分层工具以优化结果。
免疫疗法改善了具有肉瘤样和/或横纹肌样（S/R）去分化的转移性肾细胞癌（mRCC）患者的预后，这是一种侵袭性强且罕见的特征；然而，在这种情况下肾切除术的作用尚不清楚。我们发现，对于这些 mRCC 伴 S/R 去分化患者，肾切除术并未显著改善其生存或免疫治疗时间；然而，可能有一部分患者受益于这种手术方法。
