A Case of Upper Tract Urothelial Carcinoma With Neuroendocrine Differentiation Successfully Treated With Enfortumab Vedotin and Pembrolizumab

Introduction: Upper tract urothelial carcinoma with neuroendocrine differentiation (UC-NE) is extremely rare and generally associated with aggressive behavior and poor prognosis. Optimal treatment strategies remain unclear, particularly regarding the role of nectin-4-targeted therapy. Case Presentation: A 61-year-old man was diagnosed with UC-NE of the renal pelvis. Laparoscopic nephroureterectomy revealed invasive UC-NE with lymphatic invasion (pT1, G2) and carcinoma in situ of the ureter (pTis, G1). Immunohistochemistry showed strong nectin-4 expression in the urothelial component but only weak to moderate expression in the neuroendocrine component. Ten months after surgery, para-aortic and bilateral pelvic lymph node recurrence developed. Treatment with enfortumab vedotin (EV) plus pembrolizumab achieved a complete response after 3 cycles, and remission was maintained with continued therapy. Conclusion: This case suggests that EV plus pembrolizumab may be effective for UC-NE and highlights the importance of evaluating nectin-4 and the tumor immune microenvironment when considering treatment strategies for this rare subtype.