Fucosylation is an oligosaccharide modification that plays an important role in immune response and malignancy, and specific fucosyltransferases (FUTs) catalyze the three types of fucosylations: core-type, Lewis type, and H type. FUTs regulate cancer proliferation, invasiveness, and resistance to chemotherapy by modifying the glycosylation of signaling receptors. Oligosaccharides on PD-1/PD-L1 proteins are specifically fucosylated, leading to functional modifications. Expression of FUTs is upregulated in renal cell carcinoma, bladder cancer, and prostate cancer. Aberrant fucosylation in prostate-specific antigen (PSA) could be used as a novel biomarker for prostate cancer. Furthermore, elucidation of the biological function of fucosylation could result in the development of novel therapeutic targets. Further studies are needed in the field of fucosylation glycobiology in urological malignancies.

Urine-based assays currently have a limited role in the management of patients with upper tract urothelial carcinoma (UTUC), due to insufficient accuracy. This study evaluated a multiplex urine assay designed to accurately and non-invasively diagnose UTUC. Oncuria-Detect is a multiplex immunoassay capable of detecting urothelia cancer using a single voided urine specimen. In the current multi-institutional study, we tested the assay's utility in identifying UTUC in 60 subjects presenting for evaluation of upper tract mass compared with samples from 60 age-, sex-, and race-matched controls. Cancer status was confirmed via histopathological assessment of tissue specimens obtained during ureteroscopy/biopsy or at the time of definitive surgical intervention (nephroureterectomy or ureterectomy). For detecting UTUC, Oncuria-Detect provided an AUC of 0.77 (95% CI: 0.70-0.84) with an overall sensitivity of 93%, specificity of 55%, negative predictive value (NPV) 89%, and positive predictive value (PPV) 67%. Assay sensitivity values for low-grade, high-grade, non-invasive, and invasive UTUC were 94%, 93%, 93% and 92%, respectively. Voided urine cytology showed an overall sensitivity of 54%, specificity of 100%, NPV 31.0%, and PPV 100%. Selective (upper tract) cytology had a sensitivity of 80%. Oncuria-Detect outperformed both non-invasive voided urinary cytology and invasive selective cytology in overall assay performance. Oncuria-Detect accurately identified and categorized UTUC and discriminated patients with cancer from non-tumor bearing individuals. The Oncuria-Detect test provides a rapid, accurate, and non-invasive method for detecting UTUC.

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.