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

Muscle-invasive Bladder Cancer

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.

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.

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