ABSTRACT 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.
Taniguchi et al. (Thu,) studied this question.