Comprehensive Bladder Preservation Therapy on Patients With Muscle Invasive Bladder Cancer

Summary

Nowadays, Immune Checkpoint Inhibitor (ICI) has become one of the new drugs for the treatment of advanced uroepithelial carcinoma. The Food and Drug Administration (FDA) approved ICI for bladder cancer (BC) patients who cannot tolerate cisplatin chemotherapy and whose tumors express programmed cell death protein ligand-1 (PD-L1). However, the efficacy of ICI in bladder preservation therapy for muscular invasive bladder cancer (MIBC) is unknown.

With the progressive clinical confirmation of the efficacy of immunotherapy, ICI has moved from second-line to first-line treatment in the indication of advanced unresectable BC. It even has been used in the neoadjuvant and postoperative adjuvant therapy for MIBC and non-muscle invasive bladder cancer (NMIBC) where Bacillus Calmette-Guérin (BCG) therapy has failed. Available studies have shown that neoadjuvant immunotherapy can achieve a pathological complete response (pCR) of 31%-42% for MIBC, regardless of using a single drug or combination, which is higher than that of neoadjuvant chemotherapy, and the incidence of side effects associated with neoadjuvant immunotherapy is lower than that of neoadjuvant chemotherapy, providing an effective treatment option for cisplatin-intolerant patients.

Studies have shown that radiotherapy leads to immunogenic cell death, which results in the release and presentation of tumor antigens and directs the recruitment and activation of T cells. It also induces increased expression of PD-L1 in tumor cells, which in turn improves the efficacy of immunotherapy. Thus ICI combined with radiotherapy has a synergistic antitumor effect and does not produce serious toxic side effects similar to those associated with chemotherapeutic agents.

This study proposes a novel neoadjuvant immunotherapy-based integrated bladder preservation therapy (neoadjuvant immunotherapy + TURBT + postoperative adjuvant radiotherapy combined with immunotherapy) and investigates the effectiveness and safety of this strategy in bladder preservation treatment strategy.

Conditions

• Urinary Bladder Neoplasms

Interventions

DRUG

Tislelizumab Injection

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.

PROCEDURE

Transurethral resection of bladder tumor

After the initial tislelizumab injection regimen, patients undergo clinical assessment and receive transurethral resection of bladder tumor if operable.

RADIATION

Adjuvant radiotherapy

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.

Sponsors & Collaborators

• BeiGene

  collaborator INDUSTRY

• First Affiliated Hospital Xi'an Jiaotong University

  lead OTHER

Principal Investigators

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

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-02-28

Primary Completion

2024-02-29

Completion

2026-02-28

Countries

• China

Study Locations