Case Presentation of a 69-Year-Old Former Smoker with High-Grade Urothelial Carcinoma

Robert Dreicer, MD, MS, MACP, FASCO, Deputy Director and Associate Director of Clinical Research for the Cancer Center, Section Head of Solid Tumor Oncology, Hematology and Oncology, Professor of Medicine and Urology, and Co-Director of the Mellon Institute, University of Virginia, Charlottesville, Virginia, presents a case-based discussion highlighting real-world perioperative decision-making in muscle-invasive urothelial cancer, focusing on cisplatin eligibility, sequencing of systemic therapy, and the evolving role of circulating tumor DNA. The case involves a 69-year-old former smoker with high-grade urothelial carcinoma involving the muscularis propria, no radiographic metastases, and preserved performance status. Baseline renal function supports cisplatin eligibility. The patient receives four cycles of gemcitabine, cisplatin, and durvalumab and proceeds to cystectomy with lymph node dissection. Final pathology demonstrates no residual tumor in the bladder, but one microscopic positive lymph node. Postoperative imaging shows no evidence of disease, and circulating tumor DNA is initially undetectable. The panel discusses whether to continue adjuvant durvalumab and whether minimal residual disease testing should influence duration or modification of therapy. Some participants favor completing the planned durvalumab course regardless of minimal residual disease status, reflecting the trial’s design that led to approval. Others question whether serial circulating tumor DNA monitoring should alter management, particularly if conversion to positivity occurs in the absence of radiographic disease. A subsequent scenario describes conversion to circulating tumor DNA positivity six months after surgery, with imaging remaining negative. Opinions diverge regarding early therapeutic escalation versus observation, highlighting uncertainty about whether circulating tumor DNA is prognostic or predictive in this context and whether early intervention improves outcomes. An alternative case is presented with reduced renal function and an estimated glomerular filtration rate of 42 mL/min, prompting the selection of enfortumab vedotin plus pembrolizumab over cisplatin-based therapy. Similar postoperative findings raise comparable questions regarding adjuvant treatment and minimal residual disease monitoring. The discussion underscores unresolved questions regarding the duration of perioperative therapy, biomarker-guided escalation, and the balance between toxicity and potential benefit. Don't forget to join the GRU Community: https://grandroundsinurology.com/regi... Follow us on Twitter/X: https://x.com/GRUrology And like and subscribe to us here on YouTube!