Management and Treatment Strategies for Upper Tract Urothelial Carcinoma: Current Insights

Abstract: Upper tract urothelial carcinoma (UTUC) is a relatively uncommon urologic malignancy that has historically a worse prognosis than urothelial carcinoma of the bladder due to higher rate of invasion and worse morbidity in patients. However, recent developments in treatment possess great potential for improved outcomes in these patients. This review compiles the most recent practices in treating this disease, and avenues for future modalities. Risk stratification of UTUC guides treatment and surveillance, with neoadjuvant chemotherapy employed in higher stage, to improve oncologic outcome. Surgical management for UTUC includes endoscopic management (EM) and kidney-sparing surgery (KSS) for low risk (LR) disease, and radical nephroureterectomy (RNU) for high risk (HR) disease. EM may follow a retrograde or antegrade approach, preserving renal function at the cost of increased risk of recurrence. Topical therapies provide great potential for low-cost, outpatient procedures for LR disease, but their efficacy is poorly characterized. While RNU remains the gold standard, robot-assisted nephroureterectomy is the dominant modality, with lower rates of perioperative complications while maintaining comparable outcomes with respect to the open approach. Perioperative intravesical therapy is universally incorporated to reduce the risk of intravesical recurrence. The POUT trial demonstrated improved disease-free survival with adjuvant platinum-based chemotherapy following RNU, establishing it as standard of care in locally advanced disease, while enfortumab vedotin in combination with pembrolizumab has demonstrated significant improvements in progression-free and overall survival in the metastatic setting. Future implementation of biomarker technologies discloses the potential for improved screening and surveillance at low-cost. Treatment strategies for UTUC are rapidly expanding due to advances in diagnostic technologies and the emergence of novel systemic agents, including antibody-drug conjugates and immune checkpoint inhibitors. Proper management requires accurate risk stratification, with EM suitable for LR disease and RNU for HR disease. Keywords: carcinoma, urothelial, chemotherapy, upper tract urothelial carcinoma, immunotherapy, endoscopic, nephroureterectomy, ureteral neoplasms