Pathologic complete response to enfortumab vedotin plus pembrolizumab in node-positive urothelial carcinoma: a case...

Patients with advanced nodal involvement (cN2 or cN3) in urothelial carcinoma (UC) typically have poor outcomes after radical surgery. Clinical evidence on how to manage these patients following immunotherapy is limited. Major neoadjuvant trials such as KEYNOTE-B15 and NIAGARA excluded patients with multiple or bulky nodal metastases, leaving a significant gap in evidence. We present a case of a 76-year-old man with cT1 bladder cancer, concomitant distal ureteral UC (≤ cT2), and multiple enlarged right pelvic lymph nodes (cN2). After six cycles of enfortumab vedotin plus pembrolizumab (EVP), he achieved a radiologic complete response (CR) and resolution of hydronephrosis. He then underwent robot-assisted right nephroureterectomy with extended pelvic lymph node dissection using the da Vinci Xi surgical system. Pathology revealed no residual cancer in either the primary site or lymph nodes (ypT0, ypN0), with marked fibrosis suggesting a strong treatment response. There were no surgical complications, and systemic therapy was stopped after surgery. To our knowledge, this is the first reported case of pathologic complete response following EVP and robotic nephroureterectomy in a patient with node-positive UC. This case supports the potential role of surgery in select patients with excellent responses to systemic therapy who were initially considered unresectable.

The online version contains supplementary material available at 10.1007/s13691-025-00785-8.