A case of remarkable response to combined radiation therapy, enfortumab vedotin, and pembrolizumab in metastatic urothelial carcinoma.

Abstract

Enfortumab Vedotin (EV), an antibody-drug conjugate targeting Nectin-4, combined with pembrolizumab (Pem), has become a first-line therapy for locally advanced or metastatic urothelial carcinoma (la/mUC). However, the concurrent use of EV + Pem with radiotherapy (RT) remains underexplored. We report the case of a 74-year-old man with a history of robot-assisted radical cystectomy for muscle-invasive bladder cancer. Nine months post-cystectomy, the patient presented with a symptomatic calcified recurrence in the left obturator internus muscle, causing left leg numbness. The patient underwent concurrent EV + Pem therapy and RT (50 Gy in 25 fractions). Treatment was well-tolerated, with only grade 2 alopecia, grade 2 dysgeusia, and grade 1 pruritus observed. Notably, the leg numbness resolved completely by the end of RT, and imaging revealed substantial tumor shrinkage with residual calcification after two cycles of EV + Pem. This case demonstrates that concurrent administration of RT with EV + Pem can achieve significant tumor reduction and symptomatic relief without severe toxicities in la/mUC. This approach may provide a promising therapeutic strategy for managing symptomatic, radiotherapy-accessible lesions in la/mUC, warranting further investigation.