Organ-Specific Tumor Response to Enfortumab Vedotin for Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study

•This study is the first to explore the impact of organ-specific tumor response to enfortumab vedotin in patients with metastatic urothelial carcinoma.•The most prominent organ-specific response rate was found in liver metastasis, and the least in bone metastasis.•Tumor burden reduced by 50% or more in lymph node, lung, and liver metastases.•No prognostic differences were found with respect to the organ-specific overall survival. To evaluate the organ-specific therapeutic effect of enfortumab vedotin (EV) after chemotherapy and immunotherapy failed for advanced urothelial carcinoma. At 6 institutions between December 2021 and July 2023, we retrospectively analyzed patients with metastatic upper and lower urinary tract cancer who received EV monotherapy after platinum-based chemotherapy and immune checkpoint blockade therapy. Objective response rate (ORR) and organ-specific response rate (OSRR) were evaluated according to the Response Evaluation Criteria in Solid Tumors, version 1.1. This study analyzed 58 patients with 210 tumor lesions, of which 24% were females and 48% had upper urinary tract cancer. The ORR and disease control rate were 53.5% and 74.1%. Moreover, we found 15 target lesions in the primary site, 7 in local recurrence, 93 in the lymph nodes, 46 in the lung, 29 in the liver, and 20 in the bone, with OSRRs of 40%, 71.4%, 61.1%, 70.6%, 90.9%, and 18.2%, respectively. Over time from baseline, the reduction rate (median) in tumor burden was 50% or more in the lymph node, lung, and liver metastases. The organ-specific tumor response to EV in patients with metastatic urothelial carcinoma was almost favorable. The antitumor activity of EV monotherapy may be less in bone metastasis than in other organ sites. Conversely, EV showed remarkably high efficacy against liver metastasis. Advanced urothelial carcinoma with metastasis is clinically aggressive. We evaluated the organ-specific response to enfortumab vedotin treatment after platinum-based chemotherapy and immune checkpoint blockade therapy failed in patients with metastatic bladder and upper urinary tract cancer. A promising antitumor activity was observed regardless of the organ involved.