Radical Surgical Approaches to Bladder Cancer - Experts Discuss

This expert panel explores controversial and rapidly evolving questions across non–muscle-invasive and muscle-invasive urothelial cancer, including trial design, immune therapy toxicity, ctDNA-guided management, perioperative sequencing, radiation integration, and mechanisms of resistance to antibody-drug conjugates. The discussion begins with intermediate-risk non–muscle-invasive bladder cancer and whether surveillance is an appropriate control arm in phase III trials. Panelists emphasize the heterogeneity of the intermediate-risk category and note that many patients in real-world practice undergo observation alone. Regulatory requirements now mandate randomized trials rather than single-arm chemoablation studies, with observation accepted as a control in settings lacking a universally applied standard of care. Debate then shifts to immune checkpoint combinations in non–muscle-invasive disease. Panelists express concern that modest reductions in high-grade non-progressive recurrences do not justify systemic immune toxicity, particularly given the continued effectiveness of Bacillus Calmette-Guérin (BCG) in appropriately selected patients. The need to avoid overtreatment of the majority who respond to BCG is emphasized. In muscle-invasive disease, ctDNA-guided adjuvant therapy generates substantial discussion. Questions include whether to escalate therapy based on positive ctDNA in the absence of radiographic disease, the binary versus quantitative interpretation of ctDNA results, and the uncertainty regarding lead time and false negatives. Clinical judgment remains central. The panel also addresses mechanisms of resistance to enfortumab vedotin and antibody-drug conjugates, including payload resistance, linker technology, and HER2 expression thresholds. Dual-payload ADCs and improved biomarker selection are highlighted as future directions. Challenges in integrating FGFR inhibitors, targeted therapies, and radiation strategies are discussed, particularly the logistical barriers to molecular testing and treatment selection in acutely ill patients. The session underscores the tension between innovation, toxicity, biomarker uncertainty, and the need for better patient selection. 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!