Active Surveillance Versus Adjuvant Intravesical Chemotherapy in Liquid Biopsy-Defined Low-Shedding Intermediate-Risk NMIBC

NCT07749924 | Not Yet Recruiting DMC

• 1 other identifier: Truce-LB04
• Study Type: interventional
• Target: 670
• Locations: 1 country
• Sites: 5

Brief Summary

This study will evaluate whether adjuvant intravesical chemotherapy can be safely omitted under active surveillance after complete transurethral resection in selected patients with EAU intermediate-risk non-muscle-invasive bladder cancer. Patients with intermediate-risk non-muscle-invasive bladder cancer are commonly treated with transurethral resection followed by adjuvant intravesical chemotherapy to reduce the risk of recurrence. However, not all patients may derive the same benefit from additional intravesical treatment. Some tumors may have a low-shedding phenotype, meaning that they show no detectable tumor-associated signals in urine despite the presence of visible bladder tumors. In this study, preoperative urine-based liquid biopsy will be used to identify patients with a low-shedding profile. This profile is defined by negative results across urine cytology, NMP22, urinary DNA methylation, and urinary tumor DNA testing before transurethral resection. Eligible patients with EAU intermediate-risk non-muscle-invasive bladder cancer, a negative preoperative urine-based liquid biopsy profile, and complete tumor resection will be randomly assigned to active surveillance or standard adjuvant intravesical chemotherapy. The study will compare recurrence-free survival between the two groups and assess whether active surveillance can avoid immediate intravesical chemotherapy without compromising oncologic safety. Secondary outcomes will include high-grade recurrence, disease progression, need for subsequent bladder cancer treatment, safety, patient-reported outcomes.

Conditions

Bladder Cancer; Non-Muscle-Invasive Bladder Cancer (NMIBC)

Keywords

Non-muscle-invasive bladder cancer (NMIBC); Active surveillance; Liquid biopsy

Outcome Measures

Primary Outcomes (1)

• Recurrence-free survival

  Recurrence-free survival is defined as the time from randomization to the first histologically confirmed intravesical recurrence or death from any cause, whichever occurs first.

  Up to 24 months after randomization

Secondary Outcomes (6)

• High-grade recurrence-free survival

  Frame: Up to 24 months after randomization

• Progression-free survival

  Up to 24 months after randomization

• Overall Survival

  Up to 24 months after randomization

• European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire Core-30 items (EORTC-QLQ-C30) Scores

  Baseline, Weeks 6, 12, 24, 36, and 48

• European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire for Non muscle Invasive Bladder Cancer (EORTC-QLQ-NMIBC24) Scores

  Baseline, Weeks 6, 12, 24, 36, and 48

Study Arms (2)

Active Surveillance

EXPERIMENTAL

Participants assigned to this arm will undergo active surveillance after complete transurethral resection of bladder tumor. No adjuvant intravesical chemotherapy will be given. Surveillance will include scheduled cystoscopy, urine cytology, urine-based liquid biopsy testing, and other assessments according to the study protocol. Further diagnostic evaluation or treatment will be performed if recurrence or progression is suspected or confirmed.

Other: Active Surveillance

Adjuvant Intravesical Chemotherapy

ACTIVE COMPARATOR

Participants assigned to this arm will receive one year of adjuvant intravesical chemotherapy after complete transurethral resection of bladder tumor. The preferred agent is gemcitabine; mitomycin C or epirubicin may be used as protocol-allowed alternatives when gemcitabine is unavailable, contraindicated, or not routinely used at the participating center. The planned agent will be specified before randomization. Treatment will consist of an induction course of weekly intravesical instillations followed by maintenance instillations for up to 12 months, according to the study protocol.

Drug: Adjuvant Intravesical Chemotherapy

Interventions

Active Surveillance OTHER

Participants assigned to active surveillance will not receive adjuvant intravesical chemotherapy after complete transurethral resection of bladder tumor. They will undergo scheduled follow-up assessments, including cystoscopy, urine cytology, urine-based liquid biopsy testing, imaging when clinically indicated, and other evaluations according to the study protocol. Further diagnostic evaluation or treatment will be initiated if recurrence or progression is suspected or confirmed.

Active Surveillance

Adjuvant Intravesical Chemotherapy DRUG

Participants assigned to this intervention will receive one year of adjuvant intravesical chemotherapy after complete transurethral resection of bladder tumor. Gemcitabine is the preferred protocol-specified agent. Mitomycin C or epirubicin may be used as protocol-allowed alternatives when gemcitabine is unavailable, contraindicated, or not routinely used at the participating center. Treatment will include an induction course followed by maintenance intravesical instillations for up to 12 months.

Also known as: Gemcitabine, Mitomycin C, Epirubicin

Adjuvant Intravesical Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• Histologically confirmed urothelial carcinoma of the urinary bladder, including tumors with divergent differentiation, provided that the urothelial carcinoma component accounts for \>50% of the tumor
• Non-muscle-invasive bladder cancer classified as intermediate-risk according to the 2021 European Association of Urology (EAU) NMIBC prognostic risk-group definition. Intermediate-risk disease is defined as NMIBC without concomitant carcinoma in situ that does not meet the criteria for the EAU low-, high-, or very-high-risk groups.
• Complete transurethral resection of all visible bladder tumors performed within 6 weeks before randomization, with no macroscopically visible residual disease.
• Negative multi-urinary liquid biopsy results after complete TURBT and before randomization.
• Eastern Cooperative Oncology Group performance status of 0-2.
• Adequate clinical condition to undergo protocol-specified intravesical therapy, cystoscopic surveillance, and study-related procedures.
• Ability to understand the study requirements and provide written informed consent.

You may not qualify if:

• EAU low-risk, high-risk, or very-high-risk NMIBC.
• Any current or previous concomitant carcinoma in situ associated with the qualifying tumor episode.
• Muscle-invasive bladder cancer, locally advanced urothelial carcinoma, lymph-node involvement, or metastatic urothelial carcinoma.
• Incomplete TURBT, macroscopically visible residual tumor, or inability to achieve complete endoscopic resection before randomization.
• Urothelial carcinoma involving the prostatic stroma or prostatic ducts, or carcinoma in situ of the prostatic urethra.
• Severe lower urinary tract dysfunction, bladder capacity considered insufficient for intravesical treatment, or another clinically significant urological condition that may interfere with treatment or outcome assessment.
• Another active malignancy requiring systemic treatment or likely to interfere with the assessment of study endpoints, except adequately treated non-melanoma skin cancer, localized prostate cancer under surveillance, or another malignancy with a negligible risk of recurrence, as determined by the investigator.
• Pregnant or breastfeeding women.
• Any serious uncontrolled medical, psychiatric, or social condition that, in the investigator's judgment, would compromise participant safety, protocol adherence, or interpretation of study results.

Sponsors & Collaborators

• Tianjin Medical University Second Hospital: lead

Study Sites (5)

Daqing Oil General Hopital

Daqing, China

Location

Nanchang Second People's Hospital

Nanchang, China

Location

The Second Hospital of Tianjin Medical University

Tianjin, 300000, China

Location

General Hospital of Tianjin Medical University

Tianjin, China

Location

Tianjin Hospital

Tianjin, China

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms

Interventions

Watchful Waiting; Gemcitabine; Mitomycin; Epirubicin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Central Study Contacts

Hailong Hu, MD

CONTACT

+8619801518556; huhailong@tmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2026
• First Posted: August 6, 2026
• Study Start (Estimated): August 10, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2032
• Last Updated: August 6, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

CN (5)