近日，英国伦敦玛丽女王大学Thomas Powles团队研究了ctDNA引导的Atezolizumab辅助治疗肌肉浸润性膀胱癌。这一研究成果发表在2025年10月20日出版的《新英格兰医学杂志》上。

肌肉浸润性膀胱癌患者膀胱切除术后的预后各不相同。基于循环肿瘤DNA （ctDNA）的分子残留疾病检测可以识别出膀胱切除术后复发风险高的患者，这些患者可以从辅助免疫治疗中获益，从而使风险较低的患者免于不必要的治疗负担。

在一项3期、双盲、随机试验中，研究组使用连续ctDNA检测来监测（长达1年）手术后无疾病影像学证据的肌肉侵袭性膀胱癌患者。在监测期间检测ctDNA阳性的符合条件的患者以2:1的比例随机分配，每4周接受静脉注射atezolizumab或安慰剂，为期1年。主要终点是研究者评估的无病生存期。总生存率是次要终点，以分级方式评估以控制α。持续检测ctDNA为阴性的患者不接受阿特唑单抗或安慰剂。

研究组共招募761名患者；250名ctDNA检测呈阳性的合格患者接受了随机分组（167名接受atezolizumab组，83名接受安慰剂组）。Atezolizumab组的中位无病生存期为9.9个月，而安慰剂为4.8个月（首次疾病复发或死亡的风险比为0.64；95%置信区间[CI]为0.47至0.87；P=0.005）。Atezolizumab组的中位总生存期为32.8个月，而安慰剂为21.1个月（死亡风险比为0.59；95%置信区间为0.39至0.90；P=0.01）。共有28%接受atezolizumab治疗的患者和22%接受安慰剂治疗的患者出现3级或4级不良事件（7%与4%与atezolizmab或安慰剂有关）；分别有3%和2%的患者发生了致命的不良事件（2%与0%的患者与atezolizumab或安慰剂有关）。在357名持续ctDNA阴性状态的患者中，1年监测期结束时的无病生存率为95%，2年时为88%。

研究结果表明，在肌肉浸润性膀胱癌患者中，ctDNA引导的atezolizumab辅助治疗比安慰剂显著延长无病生存期和总生存期。

附：英文原文

Title: ctDNA-Guided Adjuvant Atezolizumab in Muscle-Invasive Bladder Cancer

Author: Thomas Powles, Ariel G. Kann, Daniel Castellano, Marine Gross-Goupil, Hiroyuki Nishiyama, Sergio Bracarda, Jrgen Bjerggaard Jensen, Lydia Makaroff, Shusuan Jiang, Ja Hyeon Ku, Se Hoon Park, Oscar Reig Torras, Dingwei Ye, Marco Maruzzo, Andrea Necchi, Rafael Morales-Barrera, Emilio Francesco Giunta, Jae Lyun Lee, Giampaolo Tortora, Yüksel ürün, Lukasz Dolowy, Dilek Erdem, Alvaro Pinto, Fabricio Grando, Wei Zou, Zoe June Assaf, Jacqueline Vuky, Viraj Degaonkar, Elizabeth E. Steinberg, Joaquim Bellmunt, Jürgen E. Gschwend

Issue&Volume: 2025-10-20

Abstract:

BACKGROUND

Patients with muscle-invasive bladder cancer have varied outcomes after cystectomy. Circulating tumor DNA (ctDNA)–based detection of molecular residual disease may identify patients at high risk for recurrence after cystectomy who can benefit from adjuvant immunotherapy, thus sparing patients at lower risk from unnecessary treatment burden.

METHODS

In a phase 3, double-blind, randomized trial, we used serial ctDNA testing to monitor (for up to 1 year) patients with muscle-invasive bladder cancer and no radiographic evidence of disease after surgery. Eligible patients who tested ctDNA-positive during surveillance were randomly assigned in a 2:1 ratio to receive intravenous atezolizumab or placebo every 4 weeks for up to 1 year. The primary end point was investigator-assessed disease-free survival. Overall survival was a secondary end point that was assessed in a hierarchical fashion to control for alpha. Patients who persistently tested ctDNA-negative did not receive atezolizumab or placebo.

RESULTS

A total of 761 patients were enrolled; 250 eligible patients who tested ctDNA-positive underwent randomization (167 to the atezolizumab group and 83 to the placebo group). The median disease-free survival was 9.9 months with atezolizumab, as compared with 4.8 months with placebo (hazard ratio for first event of disease recurrence or death, 0.64; 95% confidence interval [CI], 0.47 to 0.87; P=0.005). The median overall survival was 32.8 months with atezolizumab, as compared with 21.1 months with placebo (hazard ratio for death, 0.59; 95% CI, 0.39 to 0.90; P=0.01). A total of 28% of the patients who received atezolizumab and 22% of those who received placebo had adverse events of grade 3 or 4 (related to atezolizumab or placebo in 7% vs. 4%); 3% and 2% of the patients, respectively, had fatal adverse events (related to atezolizumab or placebo in 2% vs. none). Among 357 patients with persistent ctDNA-negative status, disease-free survival was 95% at the end of the 1-year monitoring period and 88% at 2 years.

CONCLUSIONS

Among patients with muscle-invasive bladder cancer, ctDNA-guided adjuvant therapy with atezolizumab led to significantly longer disease-free survival and overall survival than placebo.

DOI: NJ202510200000016

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2511885