Is Prolonged Systemic Immunotherapy Necessary After Achieving Tumor-free Status in Patients With Extensive Transurethrally Unresectable Very-high-risk NMIBC?

Randomized Trial of Active Surveillance Versus Continued Systemic Immunotherapy After Achieving Tumor-Free Status in Extensive Transurethrally Unresectable Very-High-Risk NMIBC

Patients with extensive transurethrally unresectable very-high-risk non-muscle-invasive bladder cancer (NMIBC) may achieve a tumor-free status after systemic immunotherapy-based bladder-sparing treatment combined with transurethral resection of bladder tumor (TURBT). However, the optimal duration of systemic immunotherapy after achieving a tumor-free status remains uncertain. Prolonged treatment may increase toxicity, treatment burden, and cost, while some patients may maintain durable disease control without continued therapy.

This randomized study aims to evaluate whether active surveillance after achieving tumor-free status is a feasible alternative to continued systemic immunotherapy in patients with extensive transurethrally unresectable very-high-risk NMIBC.

Patients will initially receive systemic immunotherapy-based treatment followed by disease evaluation using cystoscopy with biopsy and/or TURBT, urine cytology, urinary tumor DNA (utDNA), and imaging assessments. Patients who achieve tumor-free status after treatment and complete resection of visible disease will be randomized to either active surveillance or continued systemic immunotherapy.

The study will evaluate recurrence outcomes, bladder preservation, progression, safety, and patient management strategies following achievement of tumor-free status. The trial also aims to explore the role of urinary tumor DNA in identifying patients who may safely undergo treatment de-escalation and active surveillance.

Study Overview

• Status: Not yet recruiting
• Conditions: Non Muscle Invasive Bladder Cancer; Bladder (Urothelial, Transitional Cell) Cancer
• Intervention / Treatment: Behavioral: Active Surveillance; Drug: PD-1/PD-L1 Inhibitor-Based Systemic Immunotherapy

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hailong Hu, MD; Phone Number: +8619801518556; Email: huhailong@tmu.edu.cn
• Study Contact Backup: Name: Yunkai Qie, MD; Email: qieyunkai@tmu.edu.cn

Study Locations

• China
  • Tianjin, China
    • General Hospital of Tianjin Medical University
    • Contact: Liang Wang; Phone Number: +8615620530409; Email: wjlmnwk@163.com
  • Tianjin, China, 300000
    • The Second Hospital of Tianjin Medical University
    • Contact: Hailong Hu; Phone Number: +8619801518556; Email: huhailong@tmu.edu.cn
  • Tianjin, China
    • Tianjin Hospital
    • Contact: Guangbin Zhu; Phone Number: +8613903124399; Email: zgb2016@163.com
  • Xingtai, China
    • Xingtai People's Hospital
    • Contact: Junli Wei; Phone Number: +8617299180245; Email: wjluro@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Has histologically confirmed very-high-risk non-muscle-invasive urothelial carcinoma of the bladder.
• Has transurethrally unresectable bladder tumor, defined as visually incomplete TURBT and/or extensive high-volume disease considered unsuitable for complete and oncologically adequate transurethral resection.
• Has undergone cystoscopy and TURBT evaluation before study enrollment.
• Has received systemic PD-1/PD-L1 inhibitor-based bladder-sparing therapy before randomization.

• Has achieved tumor-free status before randomization, defined as:

  1. No visible bladder tumor on cystoscopy;
  2. Negative bladder biopsy and/or TURBT pathology;
  3. Negative urine cytology;
  4. Negative urinary tumor DNA (utDNA);
  5. No radiographic evidence of progression or metastasis.
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Has adequate organ function.
• Has provided written informed consent.

Cohort A Only

• Achieved tumor-free status at the initial response evaluation after induction systemic therapy.
• Maintained tumor-free status after additional systemic therapy before randomization.

Cohort B Only

• Did not achieve tumor-free status at the initial response evaluation because of residual non-muscle-invasive disease.
• Subsequently underwent complete TURBT/resection of residual disease followed by additional systemic therapy.
• Achieved tumor-free status at the second response evaluation before randomization.

Exclusion Criteria

• Has muscle-invasive bladder cancer (≥T2), locally advanced unresectable disease, nodal disease, or distant metastasis.
• Has concurrent upper tract urothelial carcinoma.
• Has persistent visible tumor, positive bladder pathology, positive urine cytology, or positive utDNA before randomization.
• Has received prior systemic immunotherapy for metastatic urothelial carcinoma.
• Has active autoimmune disease requiring systemic treatment.
• Is receiving systemic immunosuppressive therapy.
• Has uncontrolled infection requiring systemic therapy.
• Has another active malignancy requiring systemic treatment.
• Has known active hepatitis B, hepatitis C, human immunodeficiency virus infection, or active tuberculosis.
• Has pregnancy or breastfeeding.
• Has any medical or psychiatric condition that, in the investigator's judgment, would interfere with study participation or interpretation of results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A-1 (Cohort A Active Surveillance); Patients in Cohort A who achieve early tumor-free status after initial systemic immunotherapy-based treatment will undergo active surveillance with protocol-defined cystoscopy, urine cytology, urinary tumor DNA testing, biopsy as clinically indicated, and imaging assessments.	Behavioral: Active Surveillance; Patients undergo protocol-defined surveillance after achieving tumor-free status, including cystoscopy, biopsy as clinically indicated, urine cytology, urinary tumor DNA testing, and imaging assessments, without continued systemic PD-1/PD-L1 inhibitor therapy unless disease recurrence or progression occurs.
Active Comparator: Arm A-2 (Cohort A Continued Systemic Immunotherapy); Patients in Cohort A who achieve early tumor-free status after initial systemic immunotherapy-based treatment will continue systemic immunotherapy for a protocol-defined duration with ongoing disease surveillance.	Drug: PD-1/PD-L1 Inhibitor-Based Systemic Immunotherapy; Patients continue protocol-defined systemic PD-1/PD-L1 inhibitor therapy after achieving tumor-free status for up to approximately 1 year, with ongoing surveillance including cystoscopy, urine cytology, urinary tumor DNA testing, and imaging assessments.
Experimental: Arm B-1 (Cohort B Active Surveillance); Patients in Cohort B who do not achieve tumor-free status at initial evaluation but subsequently achieve tumor-free status after complete TURBT/resection and additional systemic immunotherapy will undergo active surveillance with protocol-defined surveillance assessments.	Behavioral: Active Surveillance; Patients undergo protocol-defined surveillance after achieving tumor-free status, including cystoscopy, biopsy as clinically indicated, urine cytology, urinary tumor DNA testing, and imaging assessments, without continued systemic PD-1/PD-L1 inhibitor therapy unless disease recurrence or progression occurs.
Active Comparator: Arm B-2 (Cohort B Continued Systemic Immunotherapy); Patients in Cohort B who subsequently achieve tumor-free status after complete TURBT/resection and additional systemic immunotherapy will continue systemic immunotherapy for a protocol-defined duration with ongoing disease surveillance.	Drug: PD-1/PD-L1 Inhibitor-Based Systemic Immunotherapy; Patients continue protocol-defined systemic PD-1/PD-L1 inhibitor therapy after achieving tumor-free status for up to approximately 1 year, with ongoing surveillance including cystoscopy, urine cytology, urinary tumor DNA testing, and imaging assessments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bladder-intact event-free survival (BI-EFS)	Time from randomization to the first occurrence of high-risk NMIBC recurrence, progression to muscle-invasive bladder cancer, distant metastasis, radical cystectomy, or death from any cause.	Up to 2 years from randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free survival (RFS)	Time from randomization to the first documented recurrence of bladder cancer or death from any cause.	Up to 2 years from randomization
Progression-free survival (PFS)	Time from randomization to progression to muscle-invasive, locally advanced, or metastatic bladder cancer, or death from any cause.	Up to 2 years from randomization
Radical cystectomy-free survival (RCFS)	Time from randomization to radical cystectomy or death from any cause.	Up to 2 years from randomization
Overall survival (OS)	Time from randomization to death from any cause.	Up to 2 years from randomization
Incidence of treatment-related adverse events	Proportion of patients experiencing treatment-related adverse events, graded according to CTCAE.	Up to 2 years from randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-Free Survival According to Urinary Tumor DNA Status	Recurrence-free survival will be evaluated according to urinary tumor DNA status after achieving tumor-free status. Urinary tumor DNA status will be assessed using a urine-based tumor DNA assay and categorized as positive or negative.	Up to 2 years from randomization
utDNA conversion during surveillance	Proportion of patients with conversion from urinary tumor DNA negative to positive during follow-up.	Up to 2 years from initial systemic administration
Bladder-Intact Event-Free Survival According to Response Cohort in the Active Surveillance Arm	Bladder-intact event-free survival will be compared between participants assigned to active surveillance in Cohort A and Cohort B.	Up to 2 years from randomization
Recurrence-Free Survival According to Response Cohort in the Active Surveillance Arm	Recurrence-free survival will be compared between participants assigned to active surveillance in Cohort A and Cohort B.	Up to 2 years from randomization
Bladder-Intact Event-Free Survival According to Response Cohort in the Continued Systemic Immunotherapy Arm	Bladder-intact event-free survival will be compared between participants assigned to continued systemic immunotherapy in Cohort A and Cohort B.	Up to 2 years from randomization
Recurrence-Free Survival According to Response Cohort in the Continued Systemic Immunotherapy Arm	Recurrence-free survival will be compared between participants assigned to continued systemic immunotherapy in Cohort A and Cohort B.	Up to 2 years from randomization

Collaborators and Investigators

• Sponsor: Tianjin Medical University Second Hospital
• Investigators: Principal Investigator: Hailong Hu, MD, Department of Urology, The Second Hospital of Tianjin Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): March 30, 2029
• Study Completion (Estimated): May 30, 2032

Study Registration Dates

• First Submitted: May 21, 2026
• First Submitted That Met QC Criteria: May 28, 2026
• First Posted (Actual): June 4, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Liquid biopsy; Non-muscle-invasive bladder cancer (NMIBC)
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms; Neoplasms; Health Services Administration; Quality of Health Care; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Watchful Waiting
• Other Study ID Numbers: Truce-LB03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No