[Perioperative Treatment with Durvalumab in Combination with Neoadjuvant Chemotherapy in Cisplatin-Eligible Patients...

Since July 2025, perioperative durvalumab combined with neoadjuvant gemcitabine/cisplatin chemotherapy followed by radical cystectomy has been approved in Germany for the treatment of muscle-invasive bladder cancer. This approval was based on the phase III NIAGARA trial, which demonstrated that the combination led to a significant improvement in event-free survival compared with neoadjuvant chemotherapy alone. Furthermore, the rate of complete pathological responses was higher with the addition of perioperative durvalumab to neoadjuvant chemotherapy. This benefit was also reflected in overall survival, which was significantly prolonged in the durvalumab combination arm. Importantly, the combination did not compromise the completion rate of cystectomy or increase surgical complication rates. This article aims to present the perioperative durvalumab-based treatment regimen in the context of the available evidence and to critically discuss its clinical benefit and limitations. A particular focus is placed on defining appropriate criteria for patient selection and characterizing the safety profile. In this context, therapy-related grade 3-4 adverse events reported in the NIAGARA trial are specifically considered, including anemia (14% in the durvalumab arm), neutropenia (14%), urinary tract infections (14%), and decreased neutrophil counts (7%). The potential role of circulating tumor DNA (ctDNA) as a prognostic biomarker is also addressed, without questioning the indication for radical cystectomy or adjuvant therapy. Finally, the article provides an outlook on novel perioperative therapeutic concepts involving the antibody-drug conjugate enfortumab vedotin and pembrolizumab for muscle-invasive bladder cancer.