肌浸润性膀胱癌的两次每日放射联合5-氟尿嘧啶/顺铂或每日放射联合吉西他滨的长期疗效——NRG/RTOG 0712的更新报告：一项随机第二阶段试验

Long-Term Results of Bladder Preservation With Twice-Daily Radiation Plus 5-Fluorouracil/Cisplatin or Daily Radiation Plus Gemcitabine for Muscle-Invasive Bladder Cancer-Updated Report of NRG/RTOG 0712: A Randomized Phase 2 Trial

INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS

影响因子:6.5

分区:医学1区 Top / 肿瘤学2区核医学2区

发表日期:2025 Jan 01

作者: John J Coen, Joseph P Rodgers, Philip J Saylor, Cheryl T Lee, Chin-Lee Wu, William Parker, Tim Lautenschlaeger, Anthony L Zietman, Jason Efstathiou, Ashesh B Jani, Omer Kucuk, Luis Souhami, Stephanie L Pugh, Howard M Sandler, William U Shipley

DOI: 10.1016/j.ijrobp.2024.08.007

摘要

肌浸润性膀胱癌的保膀治疗中，5-氟尿嘧啶/顺铂联合两次每日放射（FCT）或吉西他滨联合每日放射（GD）是有效的化放疗（CRT）方案。该试验评估了这两种方案，均在3年内表现出疗效。随访时间延长后，报告更长期的结果。患者为cT2至cT4a肌浸润性膀胱癌，随机分配接受FCT或GD，接受经尿道切除术和40 Gy的诱导CRT。完全缓解者接受64 Gy的巩固CRT，其余者进行膀胱切除。所有患者均接受辅助吉西他滨/顺铂化疗。主要终点为远处转移无疾病生存（FDM）。此次更新报告了7年的数据。毒性和疗效指标，包括膀胱完整的远处转移无疾病生存（BI-DMFS），也被评估。2008年12月至2014年4月，共入组70例，符合条件的分析病例66例，每组33例。中位随访9.1年。7年时FDM分别为65%（FCT）和73%（GD），差异无统计学意义（hazard比0.75，95%CI，0.37-1.55，P = 0.44）。膀胱完整的远处转移无疾病生存率分别为58%（95%CI，41-76）和68%（95%CI，51-84）。总生存率为48%和59%。两组中分别进行了4例和5例膀胱切除。FCT组有5例（16%）和GD组有7例（23%）患者出现3级及以上晚期毒性反应，无5级毒性。两组均保持较高的远处转移无疾病生存率，膀胱保存率低，整体存活率高，晚期毒性反应率低。吉西他滨联合每日放疗或顺铂为基础方案均为有效的膀胱保留治疗。

Abstract

For bladder-sparing treatment of muscle-invasive bladder cancer, 5-fluorouracil/cisplatin with twice-daily radiation (FCT) or gemcitabine plus daily radiation (GD) are effective chemoradiation (CRT) regimens. This trial evaluated these regimens and demonstrated efficacy with either regimen at 3 years. With further follow-up, longer-term results are reported here.Patients with cT2 to cT4a muscle-invasive bladder cancer were randomized to FCT or GD. Patients had a transurethral resection and induction CRT to 40 Gy. Patients with a complete response received consolidation CRT to 64 Gy. Others had cystectomy. Adjuvant gemcitabine/cisplatin chemotherapy was administered. The primary endpoint was freedom from distant metastasis (FDM). This updated analysis reports 7-year data. Toxicity and efficacy endpoints, including bladder-intact distant metastasis-free survival (BI-DMFS) were also assessed.From December 2008 to April 2014, 70 patients were enrolled; 66 were eligible for analysis, 33 per arm. Median follow-up was 9.1 years for eligible living patients. At 7 years, FDM was 65% and 73% for FCT and GD, respectively. Bladder-intact distant metastasis-free survival was 58% (95% CI, 41-76) and 68% (95% CI, 51-84), respectively. The post hoc hazard ratio of 0.75 (95% CI, 0.37-1.55) showed no difference between treatments (P = .44). Overall survival at 7 years was 48% and 59%. There were 4 and 5 cystectomies performed for FCT and GD, respectively. In the FCT arm, there were 5 (16%), 1 (3%), and 0 grade 3, 4, and 5 late toxicities reported, respectively. In the GD arm, there were 7 (23%), 0, and 0 grade 3, 4, and 5 late toxicities reported, respectively.Both regimens maintained high FDM rates at 7 years. Cystectomy rates were low and overall survival rates were high on both arms. Late toxicity rates were low. Either gemcitabine and daily radiation or a cisplatin-based regimen are effective bladder-sparing therapies.