Comprehensive Bladder Preservation Therapy on Patients With Muscle Invasive Bladder Cancer

This study aims to investigate the efficacy and safety of a comprehensive immunotherapy-based bladder preservation treatment strategy (neoadjuvant immunotherapy + TURBT + adjuvant radiation therapy (RT) combined with immunotherapy) by implementing a prospective, single-arm, single-center, open clinical trial.

It aims to: 1) assess pCR (pathological complete remission rate) and pathological stage reduction rate of patients with MIBC after neoadjuvant immunotherapy. 2) assess relative risk factors that have an impact on pathological stage reduction rate and pCR. 3) assess bladder preservation rate of MIBC patients after the immunotherapy-based integrated bladder preservation therapy. 4) assess tumor recurrence-free survival, progression-free survival, and tumor-specific and overall survival rates after treatment. 5) To assess the safety of this treatment. 6) To collect tumor tissues from TURBT and study genetic variations as well as the expression of relevant biomarkers.

• Tislelizumab Injection (Drug), also known as BGB-A317, BeiGene: After patient recruitment, every patient first receives a regimen of tislelizumab injection 200 mg every time , q3w, 4 times in total. Then all patients, if operable, undergo TURBT. The first day after TURBT, patients again start to receives a regimen of tislelizumab Injection 200 mg every time , q3w, 4 times in total. Meanwhile, on the eighth day after TURBT, patients start to receive radiotherapy. The total radiation dosage is 50.4 Gy (patients receive radiotherapy 28 times, dosage being 1.8 Gy every time), with the total radiation dosage on pelvis area being 45 Gy and total radiation dosage on bladder area being 50.4 Gy.
• Transurethral resection of bladder tumor (Procedure): After the initial tislelizumab injection regimen, patients undergo clinical assessment and receive transurethral resection of bladder tumor if operable.
• Adjuvant radiotherapy (Radiation): On the eighth day after TURBT, patients start to receive radiotherapy. The total radiation dosage is 50.4 Gy (patients receive radiotherapy 28 times, dosage being 1.8 Gy every time), with the total radiation dosage on pelvis area being 45 Gy and total radiation dosage on bladder area being 50.4 Gy.

Primary outcomes

• Bladder preservation rate within 1 year, % [1 year after neoadjuvant immunotherapy (Tislelizumab Injection) started]: The percentage of enrolled patients who didn't receive radical cystectomy 1 year after neoadjuvant immunotherapy (Tislelizumab Injection) started
• Pathological complete response rate after neoadjuvant immunotherapy, % [right after TURBT and pathological examination of surgical specimen has concluded.]: the percentage of enrolled patients who demonstrated pathological complete response after neoadjuvant immunotherapy, confirmed by pathological results of specimen extracted from TURBT.

Secondary outcomes

• Overall survival time, day [from the start of neoadjuvant immunotherapy to 1) death of the patients by any cause; 2) the end of followup if patients are still alive by that time; 3) last follow up date if patients are lost, whichever comes first, assessed up to 156 weeks]: the time from the start of neoadjuvant immunotherapy to 1) death of the patients by any cause; 2) the end of followup if patients are still alive by that time; 3) last follow up date if patients are lost, whichever comes first
• Adverse event [from the start of neoadjuvant immunotherapy to the last followup check, assessed up to 156 weeks]: all adverse events ever occurred to enrolled patients from the start of neoadjuvant immunotherapy to the last followup check, coded by MedDra. The severity of adverse effect will be evaluated by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.0.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age ≥ 18 years
* Voluntary participation in this trial, able to provide a written version of informed consent, and able to understand and agree to comply with the requirements of this study.
* BC patients with cT2-T4aN0M0 tumor/ lymph node/ metastasis (TNM) (AJCC 8th edition) staging based on histopathological confirmation by biopsy specimen and CT/MRI assessment.
* ECOG performance status grade less than or equal to 1

Exclusion Criteria:

* Cancer in situ (CIS) confirmed by biopsy pathology.
* Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4(CTLA)-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways (excluding BCG treatment).
* Received other approved systemic anticancer therapy or systemic immunomodulators within 28 days prior to enrollment.
* Severe chronic or active infection requiring systemic antibacterial, antifungal or antiviral therapy within 14 days prior to enrollment
* Received herbal or proprietary Chinese medicine for cancer inhibition within 14 days prior to admission.
* Received live vaccination within 28 days prior to admission.
* Has need for long-term heavy use of hormones or other immunosuppressive drugs.
* Potassium, sodium, or calcium abnormalities affecting treatment, interstitial lung disease, non-infectious pneumonia, or other uncontrolled systemic diseases, including diabetes, hypertension, or active heart disease.
* Patients with chronic hepatitis B, hepatitis B virus carriers, or active hepatitis C.
* Active, known or suspected autoimmune disease requiring systemic therapy.
* Patients with end-stage renal disease (GFR <15 mL/min) or requiring dialysis.
* Other active neoplastic disease.
* Uncontrolled severe physical or mental illness.
* Pregnant or lactating women.

• Jinhai Fan, MD, Principal investigator, First affiliated hospital of Xian jiaotong university