Efficacy of Gemcitabine Submucosal Injection for Preventing Recurrence in Intermediate- and High-Risk Non-Muscle-Invasive Bladder Cancer: A Randomized Trial

Not Applicable

Not yet recruiting

• Conditions: Non Muscle Invasive Bladder Cancer
• Interventions: Drug: Gemcitabine Submucosal Injection; Drug: Gemcitabine Intravesical Instillation

• Registration Number: NCT07198451
• Lead Sponsor: Shanghai University of Traditional Chinese Medicine

Brief Summary

Bladder cancer is the most common malignant tumor of the urinary system in China, and its incidence has been increasing year by year. It is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). NMIBC accounts for 75% of newly diagnosed bladder cancer cases, and transurethral resection of bladder tumor (TURBT) followed by postoperative intravesical therapy is the standard treatment for NMIBC. However, the 5-year recurrence rate of NMIBC remains as high as 50%, with 20-30% of patients progressing to MIBC. MIBC is characterized by rapid progression and a high tendency for metastasis. The 5-year survival rate for patients with metastatic bladder cancer is only 5.4%. This study aims to investigate the efficacy of submucosal injection of the chemotherapeutic agent gemcitabine in preventing recurrence of intermediate- and high-risk NMIBC. Additionally, it seeks to develop software and devices related to submucosal injection to promote the clinical application of this new approach in the chemotherapeutic management of NMIBC. This research is expected to bring a revolutionary breakthrough in the standardisation of whole-process diagnosis and treatment of NMIBC, holding significant scientific value and major clinical translational importance for improving therapeutic outcomes and prognosis of bladder cancer.

Detailed Description

Bladder cancer is a common malignant tumor of the urinary system. Globally, in 2023, there were approximately 610,000 new cases of bladder cancer and about 220,000 deaths attributed to the disease. In China, over the past two decades, the age-standardized incidence and prevalence rates of bladder cancer in men have increased by 71.79% and 195.38%, respectively. Over the last 15 years, the average annual mortality rate for male bladder cancer has risen by 3.84%, posing a serious threat to public health.

Bladder cancer is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) based on whether the tumor invades the muscle layer. NMIBC accounts for approximately 75% of newly diagnosed bladder cancer cases. The standard treatment for NMIBC involves transurethral resection of bladder tumor (TURBT) followed by postoperative intravesical therapy. However, NMIBC often recurs within one year, with a recurrence rate as high as 60-70%, and 20-30% of cases progress to MIBC. Once bladder cancer advances to MIBC, it is characterized by rapid progression and a high tendency for metastasis. The standard treatment for MIBC is radical cystectomy with lymph node dissection, often accompanied by neoadjuvant or adjuvant chemotherapy. Traditional radical surgery for bladder cancer is highly invasive, associated with slow postoperative recovery and a high incidence of complications. The objective response rate for neoadjuvant or adjuvant chemotherapy is less than 50%. The 5-year survival rate for MIBC is below 60%, and for patients with distant metastasis, it drops significantly to just 5.4%.

In recent years, cancer immunotherapy, particularly immune checkpoint inhibitors, has advanced rapidly. However, immunotherapy also suffers from a low objective response rate, which is even below 30% in MIBC. Therefore, the high incidence, recurrence rate, and difficulty in curing bladder cancer remain significant challenges for both clinicians and patients.

TURBT is the standard surgical procedure for NMIBC. Intravesical therapy is a local adjuvant treatment used after TURBT to prevent recurrence. However, the efficacy of intravesical therapy is limited by inadequate drug absorption, resulting in insufficient local drug concentrations and suboptimal therapeutic outcomes. Moreover, postoperative intravesical therapy involves long-term, repeated invasive procedures, which often lead to complications such as urinary tract infections, bladder irritation, and urethral strictures. Improving the efficiency of drug utilization in intravesical therapy is a promising approach to address these issues. Enhancing drug absorption and prolonging the sustained-release effect of the agents could improve treatment efficacy while reducing the frequency of intravesical instillations, ultimately improving the prognosis of NMIBC, lowering recurrence rates, and reducing the risk of progression to MIBC. Submucosal injection of chemotherapeutic drugs offers a potential solution by increasing drug utilization efficiency and reducing complications associated with intravesical therapy.

Study Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-22
• Study First Submitted QC: 2025-09-22
• Last Update Submitted: 2025-09-22
• Study First Posted: 2025-09-30
• Last Update Posted: 2025-09-30
• Study Start: 2025-10-01
• Primary Completion: 2028-05
• Study Completion: 2028-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 320

Inclusion Criteria

1. Patients aged 18 to 80 years (inclusive) with radiologically confirmed bladder tumor and scheduled to undergo transurethral resection of bladder tumor (TURBT).
2. Postoperative pathological confirmation of intermediate- or high-risk non-muscle-invasive bladder cancer (NMIBC).
3. Voluntarily participate in the study and sign the informed consent form, ensuring the patient fully understands the trial purpose, risks, and right to withdraw.

Exclusion Criteria

1. Preoperative comorbidities including detrusor overactivity, urethral stricture, urge incontinence, stress incontinence, or overflow incontinence.
2. Concurrent urogenital infectious diseases (e.g., acute urethritis, acute cystitis).
3. History of pelvic radiotherapy.
4. Receiving systemic anti-tumor therapy for any malignant tumor.
5. Severe cardiovascular disease, hepatic or renal insufficiency, or coagulation dysfunction.
6. Presence of mental illness or psychological disorders that impair normal communication.
7. Any other situation deemed by the investigator as unsuitable for participation in this clinical study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Gemcitabine Submucosal Injection Arm	Gemcitabine Submucosal Injection	Patients in this arm will receive submucosal injections of gemcitabine following transurethral resection of bladder tumor (TURBT). The regimen consists of one injection immediately after TURBT, followed by additional injections once every three months, for a total of four injections. Each injection uses 1000mg of gemcitabine. Injection sites are planned based on bladder area and common tumor locations, administered using a specialized injection gun.
Gemcitabine Intravesical Instillation Arm	Gemcitabine Intravesical Instillation	Patients in this arm will receive standard intravesical instillation of gemcitabine following TURBT. The regimen consists of one instillation immediately after surgery, followed by an induction phase of once-weekly instillations for eight weeks, and then a maintenance phase of once-monthly instillations for ten months. Each instillation uses 2000mg of gemcitabine dissolved in 50mL of normal saline, retained for 30-60 minutes.

Primary Outcome Measures

Name	Time	Method
24-month Bladder Tumor Recurrence Rate	24 months post-operation	The proportion of patients with bladder tumor recurrence confirmed by cystoscopy and tissue biopsy within 24 months after transurethral resection of bladder tumor (TURBT). The recurrence rate is calculated as: (Number of patients with confirmed recurrence in the group / Total number of analyzed patients in that group) × 100%.

Secondary Outcome Measures

Name	Time	Method
Proportion of Pathological Grade Upgrading upon Recurrence	Through study completion, up to 60 months	The proportion of patients with recurrent tumor whose pathological grade (e.g., from low-grade to high-grade) is worse than at initial diagnosis among all patients with recurrence.
Tumor Complete Response (CR) Rate	Through study completion, up to 60 months	The proportion of patients with no evidence of tumor recurrence, metastasis, or progression as confirmed by regular cystoscopy, biopsy, urinary cytology, and imaging.
Incidence of Bladder Irritation Symptoms and Gross Hematuria	Through study completion, up to 60 months	Record and compare the proportion of patients in both groups experiencing bladder irritation symptoms (e.g., frequency, urgency, dysuria) and gross hematuria post-operation.
Change in Quality of Life Core Questionnaire (QLQ-C30) Score	Through study completion, up to 60 months	Assessed using the EORTC QLQ-C30 questionnaire. It includes 5 functional scales, 3 symptom scales, and a global health status item. The change from baseline in scores will be used to evaluate the change in quality of life.
Change in Bladder Cancer-Specific Module (QLQ-BLM30) Score	Through study completion, up to 60 months	Assessed using the EORTC QLQ-BLM30 module. It evaluates bladder cancer-specific quality of life dimensions such as urinary symptoms, physical function, and psychological state. The change from baseline in scores will be used for evaluation.