Evaluating a Kidney-sparing Strategy Combining Endoscopic Surgery, Adjuvant Radiotherapy, and HER2-targeted Antibody-Drug Conjugate in High-risk Upper Tract Urothelial Carcinoma: Study Protocol for a Prospective, Multicenter, Non-randomized Comparative Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- One-Year Disease-Free Survival
研究概览
简要总结
UTUC is a cancer that develops in the lining of the kidney or ureter. The standard treatment is radical nephroureterectomy, which removes the kidney and ureter. Although this surgery can control the cancer, it permanently reduces kidney function.
Endoscopic treatment can serve as a kidney-sparing approach for low-risk UTUC; however, in high-risk patients, the high rate of upper tract local recurrence after endoscopic treatment remains the primary failure pattern. This study aims to evaluate the efficacy and safety of radiotherapy-involved kidney-sparing treatment for UTUC.
The main questions this study aims to answer are: Can this multimodal kidney-sparing strategy reduce local recurrence of UTUC compared with endoscopic treatment alone? Participants in the kidney-sparing group will: Undergo endoscopic surgery to remove the tumor; Receive systemic therapy with disitamab vedotin and toripalimab; Receive targeted radiotherapy after surgery.
Participants will undergo regular follow-up visits, including imaging examinations and endoscopic evaluations, to monitor for recurrence or disease progression.
The results of this study may help determine whether a multimodal kidney-sparing treatment strategy could become a safe and effective option for selected patients with high-risk UTUC.
详细描述
Upper tract urothelial carcinoma (UTUC) is an uncommon malignancy arising from the urothelial lining of the renal pelvis or ureter. Radical nephroureterectomy (RNU) remains the standard treatment for high-risk disease. However, removal of the entire kidney and ureter leads to permanent loss of renal function and may negatively affect long-term quality of life and eligibility for future systemic therapies. Although kidney-sparing treatment is well established for low-risk UTUC, its role in patients with high-risk disease remains uncertain.
Recent advances in systemic therapy and radiotherapy have created opportunities to explore multimodal treatment strategies aimed at improving oncological control while preserving renal function. HER2 expression appears to be relatively frequent in UTUC, and HER2-targeted antibody-drug conjugates such as disitamab vedotin have demonstrated promising activity in urothelial carcinoma. In addition, immune checkpoint inhibitors have improved outcomes in advanced urothelial malignancies. Radiotherapy has also been reported to improve locoregional tumor control in selected patients. These developments provide the rationale for integrating endoscopic tumor management with systemic therapy and selective radiotherapy as part of a comprehensive kidney-sparing strategy.
This prospective multicenter study is designed to evaluate the feasibility, safety, and preliminary oncological outcomes of a multimodal kidney-sparing treatment pathway in patients with high-risk UTUC.
The findings of this study are expected to provide prospective evidence regarding the feasibility of a multimodal kidney-sparing strategy for selected patients with high-risk UTUC and may inform the design of future confirmatory clinical trials.
Sample size considerations Given the low incidence of UTUC and the fact that kidney-sparing treatment has not yet been established as a standard-of-care for high-risk disease, the sample size calculation was primarily based on a benchmark comparison against previously published outcomes from kidney-sparing treatment cohorts. According to available literature, the reported 1-year DFS rate following endoscopic tumor ablation combined with systemic therapy was approximately 58.82% [Chen Z, Ye J, Tu X, et al. Comprehensive modalities of kidney-sparing treatment in a carefully selected cohort of localized high-risk upper tract urothelial carcinoma: a potential paradigm shift. J Clin Oncol. 2025;43(5_suppl):794-794. doi:10.1200/JCO.2025.43.5_suppl.794]. In this study, we hypothesized that the incorporation of radiotherapy into a comprehensive kidney-sparing strategy would increase the 1-year DFS to 85%. Assuming a two-sided significance level of 0.05 and a statistical power of 80%, and accounting for a 20% dropout rate due to potential loss to follow-up and pathological heterogeneity at enrollment, the required sample size was estimated at 36 patients in the kidney-sparing group.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all of the following criteria:
- •Age 18 years or older Voluntary participation with written informed consent Pathology indicating upper tract urothelial carcinoma with HER2 at least 1+ expression Clinical stage cT1-T2N0M0 based on imaging evaluation Classified as high-risk upper tract urothelial carcinoma according to European Association of Urology (EAU) criteria Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Adequate renal function with split renal function of the affected kidney ≥10 mL/min on renal dynamic scintigraphy Expected life expectancy greater than 24 months Ability and willingness to comply with study procedures and follow-up schedule
排除标准
- •Participants will be excluded if any of the following conditions are present:
- •Inability to tolerate or refusal of kidney-sparing treatment Evidence of advanced disease (≥T3), lymph node metastasis, or distant metastasis Synchronous bladder urothelial carcinoma or other urological malignancies Previous systemic anticancer therapy, including chemotherapy, targeted therapy, immunotherapy, or antibody-drug conjugates Prior radiotherapy involving the urinary tract or retroperitoneal region Severe uncontrolled comorbidities such as cardiovascular, pulmonary, neurological, psychiatric, or systemic diseases Active severe infections requiring systemic antimicrobial therapy Known immune-related disorders requiring long-term immunosuppressive treatment Pregnancy or breastfeeding Known allergy to investigational drugs used in this study Concurrent participation in another therapeutic clinical trial Indeterminate postoperative pathological diagnosis
研究组 & 干预措施
Kidney-Sparing Multimodal Treatment
Participants undergo endoscopic tumor ablation or resection using thulium fiber laser techniques. Participants without confirmed complete tumor resection will receive selective hypofractionated radiotherapy approximately one month after surgery.Postoperative systemic therapy consists of disitamab vedotin administered every three weeks for eight cycles combined with toripalimab administered every three weeks for up to one year.
干预措施: SBRT (Radiation)
结局指标
主要结局
One-Year Disease-Free Survival
时间窗: 12 months after surgery
Disease-free survival is defined as the proportion of participants who remain alive without evidence of local recurrence, upper urinary tract recurrence, intravesical recurrence, disease progression, or distant metastasis.
One-Year kidney-sparing rate
时间窗: 12 months after surgery
One-Year kidney-sparing rate is defined as the proportion of participants who do not require conversion to radical nephroureterectomy due to disease progression after initial kidney-sparing treatment.
次要结局
- Overall Survival(Up to 5 years)
- Progression-Free Survival(Up to 5 years)
- Local Recurrence-Free Survival(Up to 5 years)
- Intravesical Recurrence-Free Survival(Up to 5 years)
- Metastasis-Free Survival(Up to 5 years)
- Treatment-Related Adverse Events(From treatment initiation to 12 months)
研究者
Xuesong Li
Professor and Chief Physician, Department of Urology, Peking University First Hospital
Peking University First Hospital