Minimizing overtreatment and maximizing oncologic outcomes in upper tract urothelial carcinoma

An update on the latest advances in the management of upper tract urothelial carcinoma (UTUC), with an emphasis on strategies to optimize oncologic outcomes while minimizing overtreatment.

Recent high-quality trials have changed the landscape of UTUC treatment. Emerging tools including 3D histology and measurement of cell free tumor DNA may improve diagnostic accuracy of disease grading and staging, and be used in monitoring treatment response. Novel therapies show promise of reducing low-grade UTUC disease recurrence at the cost of significant side-effects. Platinum-based neoadjuvant chemotherapy in high-grade/muscle-invasive disease showed complete pathological response in a subset of patients, but difficult to predict responders. Adjuvant platinum-based chemotherapy exhibited a clear survival benefit, but immunotherapy did not, suggesting possible overtreatment with these agents. Molecularly-targeted therapies in metastatic UTUC have shown the greatest recent oncologic advances, but exhibit a high adverse event-rate.

Low-grade UTUC has the potential for overtreatment, as it exhibits low metastatic-potential and excellent survival. For high-grade and advanced-stage UTUC, these carry high mortality rates and require more aggressive treatment, but studies are limited by inaccurate grading and staging which can lead to overtreatment especially in the neoadjuvant setting. Emerging technologies will help improve diagnostic accuracy and noninvasive monitoring of treatment response.