上尿路尿路上皮癌根治性手术前膀胱内化疗：REBACARE试验
Intravesical Instillation of Chemotherapy Before Radical Surgery for Upper Urinary Tract Urothelial Carcinoma: The REBACARE Trial.
作者信息
van Doeveren Thomas, Remmers Sebastiaan, Boevé Egbert R, Cornel Erik B, van der Heijden Antoine G, Hendricksen Kees, Cauberg Evelyne C C, Jacobs Rens, Kroon Bin K, Leliveld Annemarie M, Meijer Richard P, van Melick Harm, Merks Bob, Oddens Jorg R, Pradere Benjamin, Roelofs Luc A J, Somford Diederik M, de Vries Peter, Wijsman Bart, Windt Willemijn A K M, Yska Marit, Zwaan Peter J, Aben Katja K H, van Leeuwen Pim J, Boormans Joost L
机构信息
Department of Urology Erasmus MC Cancer Institute University Medical Center Rotterdam Rotterdam The Netherlands.
Department of Urology Erasmus MC Cancer Institute University Medical Center Rotterdam Rotterdam The Netherlands.
出版信息
Eur Urol. 2025 Apr;87(4):444-452. doi: 10.1016/j.eururo.2024.12.006. Epub 2025 Jan 22.
BACKGROUND AND OBJECTIVE
Intravesical instillation of chemotherapy (IIC) after radical surgery for upper urinary tract urothelial carcinoma (UTUC) reduces the risk of intravesical recurrence (IVR). However, compliance is low because of possible extravesical leakage after bladder cuff excision. The aim of this study was to evaluate the efficacy of preoperative IIC in reducing the risk of IVR.
METHODS
In this prospective, single-arm, multi-institutional, phase 2 clinical trial, 190 chemonaïve patients with primary UTUC without prior or concurrent bladder cancer received a single intravesical instillation of mitomycin C for 1-2 hr within 3 h before surgery. The primary endpoint was the 2-yr histologically confirmed IVR rate, with a target reduction of >40% (from 33.2% according to literature data to <20%). A historical cohort of 247 patients with UTUC who did not receive perioperative IIC served as the reference. Secondary endpoints included compliance, toxicity, and IVR-free survival, which was analyzed via multivariable Cox regression and stratified by previous diagnostic ureteroscopy (d-URS).
KEY FINDINGS AND LIMITATIONS
The 2-yr IVR rate was 24% (95% confidence interval [CI] 18-31%) on intention-to-treat analysis and 23% (95% CI 13-32%) on per-protocol analysis. Multivariable analysis revealed that d-URS was associated with higher IVR risk. In the REBACARE cohort, patients without d-URS had threefold lower IVR risk (hazard ratio 0.33, 95% CI 0.12-0.87) in comparison to the reference cohort. Compliance with preoperative instillation was 96% and no grade >2 toxicity occurred.
CONCLUSIONS AND CLINICAL IMPLICATIONS
Preoperative IIC with mitomycin C was feasible and well tolerated and significantly reduced IVR risk for patients without d-URS. These findings suggest that preoperative IIC is a viable strategy for this subset of UTUC patients and that d-URS should be performed judiciously.
背景与目的
上尿路尿路上皮癌（UTUC）根治性手术后膀胱内灌注化疗（IIC）可降低膀胱内复发（IVR）风险。然而，由于膀胱袖口切除术后可能发生膀胱外渗漏，依从性较低。本研究的目的是评估术前IIC在降低IVR风险方面的疗效。
方法
在这项前瞻性、单臂、多机构的2期临床试验中，190例未经化疗的原发性UTUC患者，且无既往或同时存在的膀胱癌，在手术前3小时内接受单次膀胱内灌注丝裂霉素C 1 - 2小时。主要终点是2年组织学证实的IVR率，目标降低>40%（从文献数据中的33.2%降至<20%）。247例未接受围手术期IIC的UTUC患者的历史队列作为对照。次要终点包括依从性、毒性和无IVR生存期，通过多变量Cox回归分析，并根据既往诊断性输尿管镜检查（d - URS）进行分层。
主要发现与局限性
意向性分析的2年IVR率为24%（95%置信区间[CI] 18 - 31%），符合方案分析为23%（95% CI 13 - 32%）。多变量分析显示，d - URS与较高的IVR风险相关。在REBACARE队列中，与对照队列相比，未进行d - URS的患者IVR风险降低了三倍（风险比0.33，95% CI 0.12 - 0.87）。术前灌注的依从性为96%，未发生>2级毒性。
结论与临床意义
术前使用丝裂霉素C进行IIC是可行的，耐受性良好，并且显著降低了未进行d - URS患者的IVR风险。这些发现表明，术前IIC是这部分UTUC患者的可行策略，并且应谨慎进行d - URS。
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