Upper Tract Urothelial Carcinoma

This is a two-stage, prospective, single-center observational diagnostic accuracy study evaluating noninvasive urine testing for the detection of urothelial carcinoma (UC). The study enrolls adult patients presenting with gross or microscopic hematuria and imaging evidence of a space-occupying lesion in the renal pelvis, ureter, or bladder, who are scheduled for diagnostic cystoscopy and/or surgical tissue sampling. Histopathological examination serves as the reference standard. Stage 1 (Completed, 8th October 2019 - 31st December 2023): A total of 113 participants have been enrolled. Owing to sufficient research funding, all participants in this stage underwent four urine-based tests: cytology, fluorescence in situ hybridization (FISH), DNA methylation, and a 17-gene mutation panel. Stage 2 (Ongoing, from 1st January 2024): The testing protocol was refined to focus on urine DNA methylation alone, owing to limited research funding and the lower cost of DNA methylation compared with the 17-gene mutation panel. As of registration (May 2026), approximately 330 participants have been enrolled. All enrolled participants are categorized into two groups based on histopathology: a UC group (including upper tract urothelial carcinoma \[UTUC\] and bladder cancer \[BC\]) and a non-UC control group. The primary outcome is the diagnostic accuracy (area under the receiver operating characteristic curve \[AUC\] with 95% confidence interval, sensitivity, and specificity) of the four urine-based tests in the Stage 1 cohort. The key secondary outcome is the diagnostic accuracy of urine DNA methylation in the Stage 2 cohort. Other secondary outcomes include paired comparisons of AUCs among the four tests in the Stage 1 cohort. Exploratory analyses will include the diagnostic performance of urine cytology in a subset of Stage 2 participants with UTUC, as well as subgroup analyses by tumor site (UTUC vs. BC). Because this study is purely observational and non-interventional, prospective registration was not a regulatory or institutional requirement when enrollment began in 2019. This record is being submitted prior to any data analysis to ensure consistency with current research transparency standards.

The goal of this clinical trial is to learn if adding a template lymph node dissection (TLND) to the standard surgery for upper tract urothelial cancer (UTUC) can improve patient survival and prevent the cancer from recurrence. The main questions it aims to answer are: Do patients who receive standard surgery with LND live longer without their cancer returning? Is adding LND safe, and how does it affect surgery-related complications? Researchers will compare the group receiving standard surgery plus LND to the group receiving standard surgery alone to see if adding LND is more effective. Participants will: Be randomly assigned to one of the two surgical groups. Undergo their assigned surgery and recover in the hospital. Attend regular follow-up visits for checkups and scans for 5 years to monitor for cancer recurrence, with the possibility of long-term follow-up extending to 10 years.

This is a prospective, multicentre, single-arm phase II study evaluating a response-adapted kidney-preserving strategy in patients with HER2-positive high-risk upper tract urothelial carcinoma (UTUC). Patients will receive neoadjuvant disitamab vedotin plus tislelizumab, followed by response-adapted local treatment, including kidney-sparing surgery or radical nephroureterectomy based on predefined criteria. The primary objective is to assess whether this multimodal strategy can achieve clinically meaningful oncologic control while preserving renal function, as measured by 1-year kidney-intact event-free survival (KI-EFS). Secondary and exploratory objectives include evaluation of clinical response, survival outcomes, safety, renal function preservation, and longitudinal dynamics of circulating and urinary tumor DNA.

It is a prospective single-arm pilot study to investigate the safety and feasibility of flexible ureteroscopy under local anaesthesia.

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.

This study is evaluating whether a medication called 5-aminolevulinic acid (5-ALA), approved by the FDA for use in brain surgery, can help improve the visibility of upper tract urothelial tumors during surgery. Patients undergoing ureteroscopic tumor resection will receive 5-ALA prior to surgery, and surgeons will use special blue light to help identify abnormal tissue that might not be seen under standard white light. The goal is to assess whether this technique can enhance tumor detection and removal.

This randomized, open-label, multicenter phase II study is designed to compare disitamab vedotin plus radiotherapy with gemcitabine plus carboplatin as adjuvant treatment in patients with HER2-expressing upper tract urothelial carcinoma after radical nephroureterectomy (RNU). Eligible patients must have postoperative pathologic stage pT3-pT4N0M0 or pTanyN+M0, HER2 expression defined as immunohistochemistry (IHC) 1+, 2+, or 3+, and be cisplatin-ineligible. Patients will be randomized in a 2:1 ratio to receive disitamab vedotin plus radiotherapy or gemcitabine plus carboplatin. The primary endpoint is 3-year disease-free survival. Secondary endpoints include overall survival, metastasis-free survival, local recurrence-free survival, bladder recurrence-free survival, incidence of adverse events, and patient-reported quality of life.

This hypothetical first-in-human study is designed to evaluate the safety, feasibility, and preliminary anti-tumor activity of an allogeneic dual-target Nectin-4/HER2 CAR-NK cell product in adults with relapsed/refractory locally advanced or metastatic urothelial carcinoma. Based on public urothelial-cancer evidence, Nectin-4 was selected as the lead antigen because it has the strongest disease-specific clinical validation; HER2/ERBB2 was chosen as the secondary co-target to broaden tumor coverage and reduce antigen-escape risk. EpCAM is not selected as a therapeutic co-target in this example because of broader normal epithelial expression and weaker tumor specificity in urothelial carcinoma.

Prehabilitation refers to the process of improving a patient's functional capabilities prior to a surgical procedure with the goal of decreasing post-surgical inactivity and physical decline. This clinical trial evaluates the utility of a personalized home-based prehabilitation exercise intervention for the improvement of physical function and surgical outcomes in patients with urothelial carcinoma undergoing definitive or consolidative surgery of the bladder (radical cystectomy) or upper tract (nephroureterectomy, ureterectomy) with or without preceding neoadjuvant/systemic therapy. The exercise intervention includes at-home exercise sessions focused on the improvement of core strength and balance as well as personalized step count goals, delivered to patients remotely via a smart-device-based application (ExerciseRx). Encouraging physical activity before surgery may improve physical function and surgical outcomes in patients who are scheduled to undergo surgery for their bladder or urothelial cancer.

The NECTAR study is a multicenter, open-label, randomized phase II clinical trial designed to evaluate a neoadjuvant treatment strategy in patients with localized upper tract urothelial carcinoma (UTUC). In this study, eligible participants will be randomly assigned to receive either neoadjuvant treatment with toripalimab plus the investigational drug 9MW2821 followed by radical nephroureterectomy with or without lymph node dissection, or upfront radical nephroureterectomy with or without lymph node dissection as standard of care. The purpose of the study is to compare the pathologic response at the time of surgery between the two treatment approaches and to assess treatment safety. Participants will be monitored throughout treatment and follow-up for treatment response, adverse events, and other clinical outcomes. The information obtained from this study may help improve future treatment strategies for patients with localized UTUC.

A Prospective Phase II Study of Adjuvant Cisplatin-Based Chemotherapy followed by Maintenance Avelumab in Upper Tract Urothelial Carcinoma

This is a a prospective single-arm pilot study to investigate the safety and feasibility of flexible ureteroscopy under local anaesthesia. All consecutive patients who have undergone kidney-sparing surgery for managing upper tract urothelial carcinoma will be screened for study eligibility. The primary outcome is the procedural technical success rate. Secondary outcomes include the 30-day complication rate following flexible ureteroscopy, readmission rates, cost analysis, and patient-reported outcomes. Ureterorenoscopy will be conducted in the recruited patients under local anaesthesia in the ambulatory urology centre. Procedural details, technical success rates, adverse events and patient reported outcomes will be documented. The anticipated risks of this intervention are not expected to exceed those associated with the standard of care, that is ureterorenoscopy under anaesthesia. This pilot study aims to recruit a total of 10 subjects to assess the safety and feasibility of flexible ureterorenoscopy in an ambulatory care setting.

This study is designed as an open-label, single-arm, single center, phase II clinical trial, aiming to evaluate the efficacy of neoadjuvant Tislelizumab combined with Nab-Paclitaxel for patients with non-metastatic upper tract urothelial carcinoma (UTC). Patients enrolled will receive 2-3 cycles of Tislelizumab in combination with Nab-Paclitaxel every 3 weeks and then undergo radical nephroureterectomy (RNU). The assessment of efficacy is based on the histology of specimen from RNU, and treatment-related adverse events (TRAEs) will be recorded and evaluated according to CTCAE 5.0.

This multicenter, real-world study introduces a novel Hematoxylin-eosin staining(H\&E)-based four tumor microenvironment (TME) system (HEFTME system) assisting in prognostic prediction and precise adjuvant treatment selection for laUTUC postoperatively.

This study will evaluate the efficacy and safety of intravenous RC48-ADC combined with JS001 in postoperative adjuvant therapy for HER2-positive upper tract urothelial carcinoma.