Clinical trial NCT05123625: Relationship Between Lymph Node Dissection and Prognosis in High-risk NMIBC
Official title: Prognostic Effect of Whether Doing Lymph Node Dissection During Radical Cystectomy for High-risk Non-muscular Invasive Bladder Cancer: a Prospective Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bladder Cancer
Keywords: High-risk
Lymphadenectomy
Non-muscular invasive bladder cancer
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: The Second Affiliated Hospital of Kunming Medical University
name: Tianjin Medical University Second Hospital
name: RenJi Hospital
name: First Affiliated Hospital Xi'an Jiaotong University
First posted: 2021-11-17
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: There is no consensus on the need for lymph node dissection in radical cystectomy (RC) for high-risk non-muscular invasive bladder cancer (NMIBC). Investigators divided participants at high risk of NMIBC without enlarged lymph nodes as indicated by pelvic MRI into two groups 1:1. One group of participants underwent RC combined with lymph node dissection and the other group of participants only underwent RC. The incidence of complications and PFS/OS at 1, 3, and 5 years were compared.

Detailed description: Bladder cancer is highly prevalent worldwide and approximately 75% of these are non-muscle invasive bladder cancer (NMIBC). For high-risk NMIBC, postoperative intravesical chemotherapy combined with full-dose BCG for 3 years is recommended. Radical cystectomy (RC) is also one of the treatment options, and is recommended for patients with BCG-naïve, BCG-refractory, and recurrent high-grade or carcinoma-in-situ (CIS) bladder cancer after BCG perfusion.

RC combined with pelvic lymph node dissection is the standard treatment for MIBC. Currently, there is no conclusion on the radical treatment of NMIBC, most of NMIBC patients refer to MIBC and also perform pelvic lymph node dissection. However, long operation time, high incidence of lymphatic cyst, lymphatic leakage and other complications, and long recovery time, increase the psychological and economic burden. At present, many studies have showed that the positive rate of lymph nodes in NMIBC patients is low. Investigators also analyzed the data of patients who underwent RC in investigators' center from 2013 to 2019, and found that the positive rate of lymph nodes in 163 NMIBC patients was only 3.07%.

MRI can effectively predict pelvic metastatic lymph nodes, and its sensitivity and negative predictive values have been reported as high as 76.4% and 71.4%. VI-RADS score can effectively judge the muscularity of bladder tumor. Therefore, Investigators proposed whether it is necessary to perform pelvic lymph node dissection in NMIBC patients without enlarged lymph nodes indicated by pelvic MRI. Investigators intended to divide participants at high risk of NMIBC without enlarged lymph nodes as indicated by pelvic MRI into two groups 1:1. One group underwent RC combined with lymph node dissection and the other group only underwent RC. The incidence of complications and PFS/OS at 1, 3, and 5 years were compared.

Eligibility criteria: Inclusion Criteria:

1. Patients who did not undergo diagnostic transurethral resection of bladder tumor (TURBT): biopsy suggestive of G3/high grade or with CIS or cystoscopic findings of multiple, tumor diameter greater than 3 cm; and VI-RADS score of 1 or 2; and no enlarged lymph nodes detected by MRI.
2. Patients undergoing diagnostic TURBT: pathologically confirmed high-risk NMIBC, a) stage T1; b) G3 or high-grade; c) CIS; d) multiple, recurrent TaG1G2/low-grade bladder cancer patients with \>3 cm in diameter. And no enlarged lymph nodes detected on MRI.
3. Benefit from radical cystectomy as assessed by the investigator.
4. Meeting the indications for the procedure: a) absolute neutrophil count ≥ 1.5 \*109/L; b) platelets ≥ 100 \*109/L; c) hemoglobin ≥ 90 g/L; d) international normalized ratio or activated partial thromboplastin time ≤ 1.5 upper limit of normal (ULN); e) calculated creatinine clearance ≥ 1 ml/s f) serum total bilirubin ≤ 1.5 \* ULN; g) AST, ALT and alkaline phosphatase ≤ 2.5 \* ULN; h) cardiopulmonary function suggestive of tolerance to major abdominal surgery.
5. No previous history of tumor, lymph node dissection, or immune system-related disease.
6. Age 18 to 75 years.
7. No neoadjuvant therapy.
8. ECOG physical status 0 or 1.
9. Voluntary participation in this trial, ability to provide written informed consent, and understanding and agreement to comply with the requirements of this study and the evaluation schedule.

Exclusion Criteria:

1. Patients with bladder cancer ≥ T2N0M0 confirmed by pathology or assessed by imaging, or with pelvic lymph node enlargement indicated by MRI;
2. The investigator assessed patients who could not tolerate radical cystectomy;
3. Previous systemic chemotherapy or immunotherapy;
4. The presence of active autoimmune diseases requiring systemic treatment or other diseases requiring long-term use of large amounts of hormones and other immunosuppressants;
5. Had undergone major surgery or major trauma within 28 days before enrollment;
6. Received live vaccine within 28 days before enrollment;
7. Severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy within 14 days prior to enrollment;
8. Received any Chinese herbal medicine or proprietary Chinese medicine for cancer control within 14 days before enrollment;
9. Participating in other clinical studies.

Primary outcomes:
measure: PFS
timeFrame: 5 years after surgery
Secondary outcomes:
measure: OS
timeFrame: 5 years after surgery
Other outcomes:
measure: Complication rate
timeFrame: through study completion, an average of 1 year
Locations:
city: Nanjing
country: China
facility: The first affiliated hospital of Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Qiang Lu, PhD
role: STUDY_CHAIR
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