Keynote-045试验表明，治疗的长期益处（LTB）并不总是能够转化为改善无进展生存期（PFS）。里程碑生存和带有治愈期的灵活参数生存模型（FPCM）被提出作为补充统计方法，以更全面地评估治疗的LTB。本研究比较里程碑生存和FPCM分析来评估免疫检查点抑制剂（ICI）III期试验的治疗效果。从Keynote-045（尿路癌）和Checkmate-214（晚期肾细胞癌）的初步和随访分析中重建了每位患者的数据，用于PFS。每个试验都重新分析了Cox比例风险回归和两种补充方法（里程碑生存和FPCM），以估计治疗对LTB的影响。每个试验都有非比例风险的证据。对于Keynote-045试验的长期分析，FPCM鉴定了对PFS的时间依赖性影响，但Cox模型没有发现PFS有统计学差异（风险比为0.90，95％置信区间为0.75-1.08）。里程碑生存和FPCM确定了LTB分数的改善。这与基于较短随访的Keynote-045重新分析的结果一致，尽管LTB分数未被保留。Checkmate-214的PFS增加均由Cox模型和FPCM鉴定。使用里程碑生存和FPCM证明了实验性治疗依赖于LTB分数的改善。使用FPCM估计的LTB分数与较短随访期的重新分析结果一致。虽然ICI在PFS方面显示出相当大的LTB转变，但基于传统的Kaplan-Meier或Cox模型分析，我们的方法为新的治疗提供了一种替代的利益风险比评估方法，并有助于向患者传达风险。接受ICI治疗的肾脏患者可以被告知他们有潜在的治愈可能，但未来的研究需要明确证实这个结论。尽管免疫检查点抑制剂治疗在无进展生存期方面显示出相当大的LTB转变，但有必要更严格地尝试量化这种转变，而不仅仅使用Kaplan-Meier估计值或使用经典Cox模型比较无进展生存曲线。我们的结果表明，先前未接受过治疗的晚期肾细胞癌患者，通过尼伯替尤单抗和伊匹利莫（nivolumab and ipilimumab）的治疗可以实现治愈，而对于二线泌尿上皮癌则不是这种情况。Copyright © 2023欧洲泌尿器科协会。Elsevier B.V.保留所有版权。

The Keynote-045 trial illustrates that the long-term benefit (LTB) of treatment does not always translate to improved progression-free survival (PFS). Milestone survival and flexible parametric survival model with cure (FPCM) have been proposed as complementary statistical approaches to more comprehensively evaluate LTBs of treatments.The current study compares milestone survival and FPCM analyses to evaluate treatment effects of immune checkpoint inhibitor (ICI) phase III trials.Individual patient data, from initial and follow-up analyses of Keynote-045 (urothelial cancer) and Checkmate-214 (advanced renal cell carcinoma), were reconstructed for PFS.Each trial was reanalyzed using the Cox proportional hazard regression and two complementary methods (milestone survival and FPCM) to estimate treatment impact on the LTB.For each trial, there was evidence of nonproportional hazards. For the long-term analysis of the Keynote-045 trial, FPCM identified a time-dependent effect on PFS, but the Cox model found no statistical difference in PFS (hazard ratio, 0.90; 95% confidence interval, 0.75-1.08). Milestone survival and FPCM identified improvements in the LTB fractions. This was consistent with the results from the reanalysis of Keynote-045, based on the shorter follow-up, although the LTB fraction was not retained. The increase in PFS in Checkmate-214 was identified by both Cox model and FPCM. Experimental treatment-dependent improvement in the LTB fraction was demonstrated using milestone survival and FPCM. The LTB fraction estimated with FPCM was consistent with the results from the reanalysis of the shorter follow-up period.Although ICIs show substantial shifts toward LTBs in terms of PFS, based on a conventional Kaplan-Meier or Cox model analysis, our approach provides an alternative assessment of benefit-risk ratios for new therapeutics and facilitates communicating risk to patients. Kidney patients treated with ICIs can be counseled that they are potentially cured, but future work will need to definitively validate this conclusion.Although immune checkpoint inhibitor treatments show substantial shifts toward long-term benefits in terms of progression-free survival, a more rigorous attempt to quantify this shift, rather than simply using a Kaplan-Meier estimate or comparing progression-free survival curves using the classic Cox model, is warranted. Our results suggest that advanced renal cell carcinoma patients who had not received a previous treatment are functionally cured by nivolumab and ipilimumab, which is not the case for second-line urothelial carcinoma.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.