This retrospective multicenter cohort study across three Mayo Clinic sites included 28 patients who underwent consolidative radical cystectomy or nephroureterectomy after enfortumab vedotin and immune checkpoint inhibitor therapy. Before receiving enfortumab vedotin and immune checkpoint inhibitors, 13 patients (46%) had stage IV disease. Nineteen patients received enfortumab vedotin in combination with pembrolizumab. Ten patients (36%) were cisplatin-ineligible, and 11 patients (39%) had received prior cisplatin-based chemotherapy, of whom eight (29%) experienced disease progression and three (11%) experienced adverse effects prompting chemotherapy cessation.
Pathologic downstaging at surgery was observed in 23 patients (82%), including 12 patients (43%) who experienced a pathologic complete response (ypT0 N0). No patients experienced pathologic upstaging. Within 90 days, 16 patients (57%) experienced any surgical complication, of which five (18%) were Clavien-Dindo grade 3 complications. Among the 26 patients who underwent consolidative surgery with curative intent, three experienced recurrences at 3.7, 5.1, and 19.7 months after surgery, with one patient dying of urothelial carcinoma. The remaining 23 of 26 patients (89%) remained disease-free at last follow-up. Notably, 22 patients (79%) had complete cessation of systemic therapy after surgery.
The median follow-up was 10 months (interquartile range 8-17.5) from the initiation of enfortumab vedotin and immune checkpoint inhibitors and 4.5 months (interquartile range 2-7) from surgery. Study limitations include selection bias, short follow-up precluding assessment of long-term outcomes, heterogeneous treatment indications and systemic therapy sequences, and lack of universal selection criteria. Despite these limitations, this represents the largest cohort to date of patients undergoing consolidative surgery after enfortumab vedotin and/or immune checkpoint inhibitor therapy for advanced urothelial carcinoma, demonstrating that this approach is safe and feasible with promising rates of pathologic downstaging and favorable early oncologic outcomes.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
References:
- Roberson DS, Sharma V, Boorjian SA, McLeay MT 2nd, Reitano G, Nguyen MV, Orme JJ, Childs DS, Pagliaro LC, Potretzke AM, Karnes RJ, Shah P, Zganjar A, Lyon T, Tyson MD, Khanna A. Consolidative Surgery for Advanced Urothelial Carcinoma Following Induction Enfortumab Vedotin and/or Immune Checkpoint Inhibitor Therapy: A Multicenter Analysis. Eur Urol. 2025;88(2):212-214. https://doi.org/10.1016/j.eururo.2025.05.015.