Mamede Isadora, Silva Caroliny, Alves Ana Caroline, Oliveira Joao Pedro, Maia Melissa, Liz Caio Dabbous de, Oliveira Audrey Cabral de
Federal University of Sao Joao del-Rei, Divinopolis, Minas Gerais, Brazil.
Federal University of Rio Grande do Norte, Campus Universitario - Lagoa Nova, Natal, Rio Norte, Brazil.
Clin Genitourin Cancer. 2025 Feb;23(1):102288. doi: 10.1016/j.clgc.2024.102288. Epub 2024 Dec 4.
Neoadjuvant cisplatin-based chemotherapy followed by radical surgery is the standard treatment for muscle-invasive urothelial carcinoma (MIUC). The Checkmate-274 and AMBASSADOR trials have demonstrated improvements in disease-free survival (DFS) with adjuvant immunotherapy. Consequently, this meta-analysis aimed to assess the effectiveness of strategies involving checkpoint inhibitors in managing high-risk MIUC.
We searched PubMed, Embase, Cochrane, ClinicalTrials.gov, EAU24, and ASCO GU abstracts for randomized controlled trials (RCTs) comparing adjuvant PD-1 and PD-L1 inhibitors against control (placebo or observation) for MIUC. Outcomes included DFS, grade ≥3 adverse events (AEs), and overall survival (OS). Heterogeneity was assessed using I2 statistics, employing a random-effects model for analysis.
In a cohort of 2220 patients from three RCTs, 1,113 (50.14%) underwent adjuvant immunotherapy. This treatment significantly increased DFS (HR 0.76; 95% CI, 0.65-0.90; P < .01), particularly in lower tract tumors (HR 0.71; 95% CI, 0.56-0.91; P < .01). No substantial DFS improvement surfaced in the upper tract subgroup (P = .28) (p-interaction = .01). PD-L1 status (p-interaction = .83) and previous neoadjuvant chemotherapy (p-interaction = .11) did not significantly affect outcomes. However, immunotherapy correlated with higher grade ≥3 AEs (RR 1.47; P < .01), with no notable difference in OS (P = .07).
Adjuvant PD-1/PD-L1 inhibitors notably enhance MIUC DFS, particularly in lower tract tumors, regardless of PD-L1 status. These findings support immunotherapy, especially anti-PD1, as a valuable adjuvant treatment strategy for high-risk MIUC patients.
基于顺铂的新辅助化疗后行根治性手术是肌层浸润性尿路上皮癌（MIUC）的标准治疗方法。Checkmate - 274和AMBASSADOR试验已证明辅助免疫治疗可改善无病生存期（DFS）。因此，本荟萃分析旨在评估涉及检查点抑制剂的策略在管理高危MIUC中的有效性。
我们检索了PubMed、Embase、Cochrane、ClinicalTrials.gov、EAU24和ASCO GU摘要，以查找比较辅助性PD - 1和PD - L1抑制剂与对照（安慰剂或观察）用于MIUC的随机对照试验（RCT）。结果包括DFS、≥3级不良事件（AE）和总生存期（OS）。使用I²统计量评估异质性，采用随机效应模型进行分析。
在来自三项RCT的2220名患者队列中，1113名（50.14%）接受了辅助免疫治疗。这种治疗显著提高了DFS（HR 0.76；95% CI，0.65 - 0.90；P <.01），特别是在下尿路肿瘤中（HR 0.71；95% CI，0.56 - 0.91；P <.01）。在上尿路亚组中未出现显著的DFS改善（P =.28）（P交互作用 =.01）。PD - L1状态（P交互作用 =.83）和先前的新辅助化疗（P交互作用 =.11）对结果没有显著影响。然而，免疫治疗与更高的≥3级AE相关（RR 1.47；P <.01），OS无显著差异（P =.07）。
辅助性PD - 1/PD - L1抑制剂显著提高MIUC的DFS，特别是在下尿路肿瘤中，无论PD - L1状态如何。这些发现支持免疫治疗，尤其是抗PD1，作为高危MIUC患者的一种有价值的辅助治疗策略。
