Recurrent Invasive Clear Cell Subtype of Upper Tract Urothelial Carcinoma Responding to Enfortumab Vedotin and Pembrolizumab After Chemotherapy: A Case Report.

INTRODUCTION: Urothelial carcinoma (UC) with clear cell subtype is a malignant neoplasm characterized by a distinctive morphological pattern featuring a glycogen-rich cytoplasm. Due to its extremely rare occurrence in the upper urinary tract, an optimal treatment has not yet been established. CASE PRESENTATION: This study reports the case of an 81-year-old woman diagnosed with upper tract urothelial carcinoma (UTUC) with clear cell subtype located in the right renal pelvis. The patient underwent laparoscopic radical nephroureterectomy, and pathological findings showed that clear-cell morphology accounted for more than 90% of the tumor. Gemcitabine and carboplatin were administered as adjuvant chemotherapy. However, 3 months after completing adjuvant chemotherapy, the patient developed severe pain, and imaging examinations revealed metastasis to the para-aortic lymph nodes and retroperitoneum. Subsequently, the patient underwent systemic therapy with enfortumab vedotin (EV) and pembrolizumab (EV-P). Following a single cycle of EV-P, the patient exhibited substantial improvement in symptoms, and metastatic lesions decreased notably. Immunohistochemical testing confirmed strong expression of Nectin-4 in the tumor tissue. CONCLUSIONS: This is the first report to demonstrate the efficacy of EV-P for recurrent UTUC with clear cell subtype. In tumors exhibiting rare histological variants, the identification of biomarkers such as nectin-4 suggests their potential to guide effective treatment selections.