Phase II Trial of Risk-Enabled Therapy After Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer (RETAIN 1).

IF 42.1 1区 医学 Q1 ONCOLOGY Journal of Clinical Oncology Pub Date : 2025-03-20 Epub Date: 2024-12-16 DOI:10.1200/JCO-24-01214
Daniel M Geynisman, Philip H Abbosh, Eric Ross, Matthew R Zibelman, Pooja Ghatalia, Fern Anari, James R Mark, Lambros Stamatakis, Jean H Hoffman-Censits, Rosalia Viterbo, Richard E Greenberg, Thomas M Churilla, Eric M Horwitz, Mark A Hallman, Marc C Smaldone, Robert Uzzo, David Y T Chen, Alexander Kutikov, Elizabeth R Plimack
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Abstract

Purpose: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy is the standard of care for patients with muscle-invasive bladder cancer (MIBC). Mutations in DNA damage repair genes are associated with pathologic downstaging after NAC. We hypothesized that a combination of biomarker selection and clinical staging would identify patients for cystectomy-sparing active surveillance (AS).

Patients and methods: We conducted a single-arm, phase II, noninferiority trial to evaluate a risk-adapted approach for MIBC. Patients with cT2-T3N0M0 MIBC underwent NAC with accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC). Pre-NAC transurethral bladder tumor specimens were sequenced for mutations in ATM, ERCC2, FANCC, and RB1. Patients with ≥1 mutation and cT0 post-NAC began AS. The primary end point was metastasis-free survival (MFS) at 2 years for the entire cohort with the null hypothesis rejected if the lower bound exact one-sided 95% CI exceeds 64%.

Results: Seventy patients were enrolled, 33 (47%) had a mutation, and 25 (36%) began per-protocol AS. With a median follow-up of 40 months, the 2-year MFS for all patients was 72.9% (lower bound exact one-sided 95% CI, 62.8). The 2-year MFS was 76.0% in the AS group (95% CI, 54.2 to 88.4) and 71.1% (95% CI, 55.5 to 82.1) in the remaining patients. In the AS group, 17 patients (68%) had some recurrence and 12 (48%) were metastasis-free with an intact bladder. The 2-year overall survival (OS) was 84.3% (95% CI, 73.4 to 91.0); OS was 88.0% (95% CI, 67.3 to 96.0) and 82.2% (95% CI, 67.6 to 90.7) in the AS and not-AS groups, respectively.

Conclusion: Patients with MIBC treated with AMVAC followed by a risk-adapted approach to local consolidation achieved a 2-year MFS rate of 73%. The primary end point was not met, but 17% of all enrolled patients and 48% of the AS group avoided cystectomy without metastatic disease.

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肌肉浸润性膀胱癌新辅助化疗后风险激活治疗的II期试验(RETAIN 1)。
目的:以顺铂为基础的新辅助化疗(NAC)后进行膀胱切除术是肌层浸润性膀胱癌(MIBC)患者的标准治疗方法。DNA 损伤修复基因突变与 NAC 后的病理分期有关。我们假设,将生物标志物选择与临床分期相结合,可以确定哪些患者可以接受保留膀胱切除术的主动监测(AS):我们进行了一项单臂、II 期、非劣效试验,以评估 MIBC 的风险适应方法。cT2-T3N0M0 MIBC患者接受了加速甲氨蝶呤、长春新碱、多柔比星和顺铂(AMVAC)的NAC治疗。对NAC前经尿道膀胱肿瘤标本进行测序,以检测ATM、ERCC2、FANCC和RB1的突变。突变≥1且NAC后cT0的患者开始接受AS治疗。主要终点是整个队列的2年无转移生存期(MFS),如果下界精确的单侧95% CI超过64%,则拒绝零假设:70名患者入组,其中33人(47%)有突变,25人(36%)开始按协议进行AS治疗。中位随访时间为 40 个月,所有患者的 2 年 MFS 为 72.9%(下限精确单侧 95% CI,62.8)。AS组的2年MFS为76.0%(95% CI,54.2至88.4),其余患者的2年MFS为71.1%(95% CI,55.5至82.1)。在AS组中,有17名患者(68%)复发,12名患者(48%)无转移且膀胱完整。2年总生存率(OS)为84.3%(95% CI,73.4至91.0);AS组和非AS组的OS分别为88.0%(95% CI,67.3至96.0)和82.2%(95% CI,67.6至90.7):结论:MIBC患者接受AMVAC治疗后,采用风险适应方法进行局部巩固治疗,2年MFS率达到73%。虽然未达到主要终点,但在所有入组患者中,有17%的患者和48%的AS组患者避免了膀胱切除术,且未出现转移性疾病。
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来源期刊
Journal of Clinical Oncology
Journal of Clinical Oncology 医学-肿瘤学
CiteScore
41.20
自引率
2.20%
发文量
8215
审稿时长
2 months
期刊介绍: The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.
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