Mantia Charlene M, Jegede Opeyemi A, McDermott David F, Heng Daniel Y C, Xie Wanling, Choueiri Toni K, Atkins Michael B, Regan Meredith M
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA.
Department of Medicine, Harvard Medical School, Boston, MA.
JCO Oncol Pract. 2025 Jul 14:OP2500089. doi: 10.1200/OP-25-00089.
In the era of prolonged survival for advanced renal cell carcinoma (aRCC) with standard-of-care first-line therapy now including immune checkpoint inhibitor, re-evaluation of the Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic RCC Database Consortium (IMDC) prognostic models is overdue.
Data from 1,052 patients with aRCC treated on the CheckMate-214 phase III randomized trial with first-line nivolumab + ipilimumab or sunitinib were analyzed after minimum 5 years of follow-up. The end point was overall survival (OS). To investigate long-term prognostication with each treatment approach, model performance based upon continuous risk score was assessed in a time-dependent manner of increasing 6-month intervals and globally over full follow-up, using discrimination concordance (c)-indices.
With time-dependent assessment, the IMDC and MSKCC models maintained their performance over approximately 2 years from sunitinib initiation (c ≥0.69 through 18-24 months); thereafter, the models' performances with long-term OS attenuated. Over full follow-up, the models' discrimination was c = 0.66 (95% CI, 0.658 to 0.664) and c = 0.64 (95% CI, 0.640 to 0.645), respectively, for the sunitinib group. After nivolumab + ipilimumab initiation, the IMDC and MSKCC models' global discrimination was c = 0.63 (95% CI, 0.628 to 0.634) and c = 0.61 (95% CI, 0.607 to 0.614), respectively. The models' performances were attenuated in the short term (c ranging 0.64-0.69 through 18-24 months) and the long term.
This retrospective analysis of the CheckMate-214 trial, in which nivolumab + ipilimumab improved survival versus sunitinib with 48% and 37% of patients, respectively, surviving beyond 5 years, confirmed the strength of the models' prognostication for the early years after first-line sunitinib initiation continuing to stratify three prognostic categories, but also diminished discrimination among long-term survivors and with initiation of nivolumab + ipilimumab. As novel treatments are developed and patients with aRCC live longer, new models to estimate long-term prognosis are needed.
在晚期肾细胞癌（aRCC）长期生存的时代，目前标准一线治疗包括免疫检查点抑制剂，对纪念斯隆凯特琳癌症中心（MSKCC）和国际转移性肾细胞癌数据库联盟（IMDC）预后模型进行重新评估已迫在眉睫。
对CheckMate-214 III期随机试验中接受一线纳武利尤单抗+伊匹木单抗或舒尼替尼治疗的1052例aRCC患者的数据进行分析，随访时间至少5年。终点为总生存期（OS）。为了研究每种治疗方法的长期预后，基于连续风险评分的模型性能以6个月为间隔逐步增加的时间依赖性方式进行评估，并在整个随访期间进行整体评估，使用鉴别一致性（c）指数。
通过时间依赖性评估，IMDC和MSKCC模型在舒尼替尼开始使用后的大约2年内保持其性能（18至24个月内c≥0.69）；此后，模型在长期OS方面的性能减弱。在整个随访期间，舒尼替尼组模型的鉴别能力分别为c = 0.66（95%CI，0.658至0.664）和c = 0.64（95%CI，0.640至0.645）。在开始使用纳武利尤单抗+伊匹木单抗后，IMDC和MSKCC模型的整体鉴别能力分别为c = 0.63（95%CI，0.628至0.634）和c = 0.61（95%CI，0.607至0.614）。模型性能在短期（18至24个月内c范围为0.64 - 0.69）和长期均减弱。
对CheckMate-214试验的这项回顾性分析中，纳武利尤单抗+伊匹木单抗与舒尼替尼相比改善了生存率，分别有48%和37%的患者存活超过5年，证实了模型在一线舒尼替尼开始使用后的早期预后预测能力，继续将患者分为三个预后类别，但在长期幸存者之间以及开始使用纳武利尤单抗+伊匹木单抗后鉴别能力有所下降。随着新治疗方法的开发以及aRCC患者寿命延长 需要新的模型来估计长期预后。
