需要优化中风险非肌层侵犯性膀胱癌（IR-NMIBC）的治疗策略。本试验旨在比较使用COMBAT膀胱循环系统在43℃下进行30和60分钟的辅助膀胱内丝裂霉素C（MMC）治疗正常温度或高温下的无复发幸存率（RFS）。该前瞻性开放标签III期随机对照试验（HIVEC-1）在2014年至2020年期间在西班牙的13个中心开展。完全经尿道切除后立即进行MMC灌注的IR-NMIBC患者进行随机分组（1：1：1），分别进行四周后随三个月共40毫克MMC灌注正常体温（对照组；n = 106），43℃进行30分钟（n = 107）或60分钟（n = 106）的治疗。治疗依从性定义为实施四次或更多次灌注。 主要结果为意图治疗（ITT）和按照方案治疗（PP）人群在24个月RFS。次要结果包括24个月无进展生存率、安全性结果措施和健康相关生命质量的改变。采用log-rank、Fisher、χ2和方差分析等检验方法。 ITT 24个月RFS对照组为77％，43℃-30分钟组为82％，43℃-60分钟组为80％（p = 0.6）。PP 24个月RFS对照组为77％，43℃-30分钟组为83％，43℃-60分钟组为80％（p = 0.59）。6名患者在ITT人群中发展为肌层侵犯性疾病（对照组、43℃-30分钟组和43℃-60分钟组各有四名），而PP人群中有四例（全部为对照组）。有26名患者发生了严重不良事件（8.1％），我们未能在组间证明有差异（p = 0.5）。124名患者（对照组33％，43℃-30分钟组35％和43℃-60分钟组48％）发生了不良事件，主要为排尿困难和痉挛（p = 0.05）。总前列腺症状评分恶化了1.2 ± 7.3分，各组差异不大（p = 0.29）。癌症治疗功能评估-膀胱领域和指数未显示出明显改变。 在中风险非肌层侵犯性膀胱癌患者中，使用COMBAT系统进行四个月的辅助高温MMC治疗30和60分钟耐受性良好，但我们未能证明其在24个月的功效优于常温MMC。需要进一步评估长期复发和进展以及维持治疗方案。版权所有©2022欧洲泌尿外科学会。由Elsevier B.V.出版保留所有权利。

Optimising therapeutic strategies of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC) is needed.To compare recurrence-free survival (RFS) with adjuvant intravesical mitomycin C (MMC) at normothermia or hyperthermia using the COMBAT bladder recirculation system at 43 °C for 30 and 60 min.A prospective open-label, phase 3 randomised controlled trial (HIVEC-1) accrued across 13 centres between 2014 and 2020 in Spain. After complete transurethral resection of the bladder and immediate postoperative MMC instillation, patients with IR-NMIBC were randomised (1:1:1) to four weekly followed by three monthly 40-mg MMC instillations at normothermia (control; n = 106), 43 °C for 30 min (n = 107), or 43 °C for 60 min (n = 106) were investigated. Therapeutic compliance was defined as four or more instillations.The primary outcome was RFS at 24 mo in the intention-to-treat (ITT) and per-protocol (PP) populations. The secondary outcomes included progression-free survival at 24 mo, safety outcome measures, and changes in health-related quality of life. Log-rank, Fisher, χ2, and analysis of variance tests were used.The ITT 24-mo RFS was 77% for control, 82% for 43 °C-30 min, and 80% for 43 °C-60 min (p = 0.6). The PP 24-mo RFS was 77% for control, 83% for 43 °C-30 min, and 80% for 43 °C-60 min (p = 0.59). Six patients progressed to muscle-invasive disease in the ITT population (four in the control, 43 °C-30 min, and 43 °C-60 min groups each) and four in the PP population (all controls). Serious adverse events occurred in 26 patients (8.1%), and we were unable to demonstrate a difference between groups (p = 0.5). Adverse events, mainly dysuria and spasms, occurred in 124 patients (33% in control, 35% in 43 °C-30 min, and 48% in 43 °C-60 min; p = 0.05). The total International Prostate Symptom Score worsened by 1.2 ± 7.3 points, similarly across groups (p = 0.29). The Functional Assessment of Cancer Therapy-Bladder domains and indexes showed no significant change.Four-month adjuvant hyperthermic MMC using the COMBAT system for 30 and 60 min in IR-NMIBC is well tolerated, but we did not find it to be superior to normothermic MMC at 24 mo.We were unable to demonstrate the effectiveness of hyperthermia using the COMBAT system in intermediate-risk non-muscle-invasive bladder cancer. Further evaluation of long-term recurrence and progression, and maintenance regimens appears mandatory.Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.