On preoperative systemic treatment of muscle-invasive bladder cancer

Dorp, J. van (2025)

Doctoral Thesis

Treatment with neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy is the default treatment for muscle-invasive bladder cancer. However, with the encouraging results of immune checkpoint inhibitiors directed against PD-1/PD-L1 and CTLA-4 in recent years, the treatment landscape of bladder cancer is rapidly changing. In Chapter 2 we review the recent advancements in treatment with immune checkpoint inhibitors in bladder cancer and the relation with the tumor immune micro-environment. In Chapter 3 we aim to predict pathological response after neoadjuvant platinum-based chemotherapy based on the genomic biomarkers ERCC2, ERBB2, ATM, FANCC and RB1. In Chapter 4 we retrospectively investigate the effects of neoadjuvant platinum-based chemotherapy on the tumor-immune microenvironment in muscle-invasive bladder cancer patients. In Chapter 5 we describe the results of cohort 2 of the NABUCCO trial, where patients were randomized to receive either of two different dosing regimens of ipilimumab and nivolumab. In addition, we set out to predict pathological response and clinical outcome based on circulating tumor DNA in plasma and urine. In Chapter 6 we retrospectively assess the prostate tissue that was part of the radical cystoprostatectomy specimens from NABUCCO cohort 1.

• Bladder cancer
• Systemic therapy
• Chemotherapy
• Immunotherapy
• Immune checkpoint inhibition
• Tumor immune micro-environment
• Circulating tumor-DNA

• All authors: Dorp, J. van
• Supervisor: Haanen, J.B.A.G.
• Co-supervisor: Heijden, M.S. van der
• Committee: Pelger, R.C.M.; Zuur, C.L.; Blank, C.; Boormans, J.L.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2025-01-10
• ISBN (print): 9789464962437