Muscle-invasive bladder cancer (MIBC) has a high risk of recurrence following radical cystectomy. Neoadjuvant cisplatin-based chemotherapy has been used for decades to lower recurrence rates but a significant proportion of patients still have disease relapse. Recently, immune-checkpoint inhibitors (ICIs) have been evaluated for patients with MIBC, with some success. This has led to regulatory approval of adjuvant nivolumab, sandwich perioperative durvalumab and sandwich perioperative pembrolizumab with enfortumab vedotin. This review summarizes the history of practice-informing and practice-changing neoadjuvant, adjuvant and sandwich perioperative application of ICIs for MIBC, looks ahead to the promising developments in other ICI-based sandwich perioperative regimens, and highlights controversies surrounding overtreatment versus undertreatment and the need for predictive biomarkers.
This review discusses how immune-checkpoint inhibitors (ICIs), which are drugs that empower your own immune system to fight cancer, are being integrated into the treatment of muscle-invasive bladder cancer. The review assesses various clinical trials to see how these drugs work when given at different stages of the surgical process: before the operation, after the operation, or both. It also explores the next generation of treatments such as combining immunotherapy with antibody–drug conjugates (ADCs).
For decades, the standard treatment was chemotherapy followed by surgery. However, this approach has two major flaws:High recurrence: many patients still see their cancer return within a few years.Ineligibility: many patients are too frail or have kidney issues that prevent them from receiving standard chemotherapy (cisplatin).This article is important because it highlights a paradigm shift. New drug combinations are proving to be more effective and less toxic, offering hope to patients who previously had very limited options.The review breaks down the ‘new era’ of bladder cancer care into three main pillars: timing of treatment, antibody–drug conjugates and precision monitoring with ctDNA.
The medical community is testing the best time to use these drugs:Neoadjuvant (before surgery): shrinking the tumour to make surgery more successful. Trials like PURE-01 showed that some tumours disappeared entirely before surgery.Adjuvant (after surgery): cleaning up microscopic cancer cells. Nivolumab is now a standard option here to prevent the cancer from returning.Sandwich (perioperative): a ‘before-and-after’ achieving excellent results. The NIAGARA trial recently led to the approval of durvalumab, which is given both before and after surgery to maximize survival.
ADCs (like enfortumab vedotin) deliver chemotherapy directly to cancer cells while sparing healthy tissue. When combined with immunotherapy, these drugs are outperforming traditional chemotherapy.
Liquid biopsies (sensitive blood tests that look for circulating tumor DNA) are being used to test patients.If the test is positive: The patient likely needs aggressive immunotherapy.If the test is negative: In the future, these patients might be able to skip extra treatments, avoiding unnecessary side effects and costs.While surgery remains a cornerstone of treatment, the addition of immunotherapy and ADCs is significantly increasing survival rates and finally providing effective options for patients who cannot tolerate traditional chemotherapy.
Drugs in context. 2026 Jun 19*** epublish ***
Albert Jang, Abby L Grier, Iris Y Sheng, Shahla Bari, Pedro C Barata, Jorge A Garcia, Jason R Brown
Division of Solid Tumour Oncology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA., School of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.