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

## TL;DR

A rare case of upper tract urothelial carcinoma with neuroendocrine features was successfully treated with a combination of enfortumab vedotin and pembrolizumab.

## Contribution

This case demonstrates the potential effectiveness of enfortumab vedotin plus pembrolizumab in treating a rare and aggressive cancer subtype.

## Key findings

- Enfortumab vedotin plus pembrolizumab achieved a complete response in a patient with UC-NE.
- Nectin-4 expression was strong in the urothelial component but weak in the neuroendocrine component.
- The treatment combination maintained remission after three cycles.

## Abstract

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.

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.

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.

Upper tract urothelial carcinoma with neuroendocrine differentiation is exceedingly rare and associated with unclear treatment strategies.Although the neuroendocrine component demonstrated weak to moderate nectin‐4 expression, enfortumab vedotin plus pembrolizumab induced a complete response.This case indicates that enfortumab vedotin plus pembrolizumab may be effective for urothelial carcinoma with neuroendocrine differentiation.

Upper tract urothelial carcinoma with neuroendocrine differentiation is exceedingly rare and associated with unclear treatment strategies.

Although the neuroendocrine component demonstrated weak to moderate nectin‐4 expression, enfortumab vedotin plus pembrolizumab induced a complete response.

This case indicates that enfortumab vedotin plus pembrolizumab may be effective for urothelial carcinoma with neuroendocrine differentiation.