Remodeling of MHC-related Immune Microenvironment in MIBC After Neoadjuvant Therapy

An Exploratory Study on the Remodeling of MHC-related Tumor Immune Microenvironment in Patients With Muscle-invasive Bladder Cancer After Neoadjuvant Therapy

In this study, the relevant biomarkers for predicting the efficacy of neoadjuvant therapy in patients with MIBC were further explored. Meanwhile, the dynamic molecular monitoring of neoadjuvant therapy in MIBC patients and the treatment guidance based on the MHC tumor immune microenvironment were also explored to select the treatment plan based on relevant biomarkers for subsequent immunotherapy in MIBC patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Muscle-invasive Bladder Cancer
• Intervention / Treatment: Drug: Immunotherapy plus chemotherapy

Detailed Description

Bladder cancer is one of the most common malignant tumors of the urinary system. Although approximately 70% of newly diagnosed cases are non-muscle-invasive bladder cancer (NMIBC), nearly 90% of them will recur within five years. Once the disease progresses to muscle-invasive bladder cancer (MIBC), the five-year survival rate drops to about 47%, and the rate for distant metastasis is as low as 5%.

Radical cystectomy (RC) is the standard surgical treatment for MIBC. However, Zehnder et al., in a review of surgical cases over 30 years, found that it did not significantly improve survival rates. Over the past two decades, cisplatin-based neoadjuvant chemotherapy has accumulated substantially stronger evidence compared to adjuvant chemotherapy after surgery. One of the largest case studies indicated that neoadjuvant chemotherapy significantly improves the 10-year survival rate. Since May 2016, the U.S. FDA has approved five PD-1/PD-L1 inhibitors for the second-line treatment of advanced urothelial carcinoma, as well as Atezolizumab (IMvigor210, cohort 1) and Pembrolizumab (KEYNOTE-052) for first-line treatment in patients ineligible for cisplatin-based chemotherapy, marking the beginning of a new era in systemic therapy for advanced urothelial carcinoma. With growing understanding of immune mechanisms, clinical research on immunotherapy for bladder cancer has gradually expanded to include combinations with chemotherapy, radiotherapy, targeted therapy, and preoperative neoadjuvant applications. Among these, the results of the PURE-01 and ABACUS studies on neoadjuvant immunotherapy prior to RC are particularly encouraging.

This study prospectively plans to enroll 30 patients with muscle-invasive bladder cancer. These patients will receive standard systemic therapy combined with immunotherapy. The research aims to explore the correlation between the remodeling of the tumor immune microenvironment and patient prognosis and treatment efficacy. Furthermore, there remains a lack of biomarkers for predicting the efficacy of neoadjuvant therapy in MIBC patients. This study will further investigate potential biomarkers for predicting treatment response to neoadjuvant therapy in MIBC patients. It will also explore dynamic molecular monitoring during neoadjuvant treatment and treatment guidance based on the MHC-related tumor immune microenvironment. The ultimate goal is to facilitate treatment selection for MIBC patients receiving immunotherapy based on relevant biomarkers.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Xiongjun Ye; Phone Number: 13910380916; Email: yexiongjun@cicams.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Muscle-invasive bladder cancer

Description

Inclusion Criteria:

• Male or female, aged ≥18 years.
• Expected survival ≥12 weeks.
• Diagnosed by histopathology as muscle-invasive bladder urothelial carcinoma (MIBC) without upper urothelial carcinoma.
• Clinical stage (cT2-T4a, N0-1, M0) and no distant metastasis as evaluated by imaging.
• The subjects were assessed by urologists as tolerable and planned radical cystectomy.
• ECOG Physical Condition 0-2.

Exclusion Criteria:

• Patients with previous malignant tumors were not eligible to participate in the study unless they had achieved complete remission for at least 5 years prior to enrollment and did not require additional treatment or did not require additional treatment during the study.
• Combined with serious internal medical diseases including but not limited to: uncontrolled diabetes, active peptic ulcer, active bleeding, etc.
• Patients with insufficient communication, understanding and cooperation, or poor compliance, cannot be guaranteed to complete follow-up as required.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR	The pathological complete response (pCR) rate evaluated by the pathological laboratory	immediately after the intervention/procedure/surgery

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Study Chair: Xiongjun Ye, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: September 16, 2025
• First Submitted That Met QC Criteria: February 25, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics; Biological Therapy; Immunomodulation; Drug Therapy; Immunotherapy
• Other Study ID Numbers: NCC4928

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No