Upper Tract Urothelial Carcinoma (UTUC) Diagnosis and Risk Stratification: A Comprehensive Review

SIMPLE SUMMARY: To choose the appropriate treatment for patients with upper tract urothelial carcinoma (UTUC), proper diagnosis and risk assessment of the disease is mandatory. This study reviews some of the diagnostic tools, and the patient- and disease-related prognostic factors that affect the outcome. Predictive tools designed by these factors help determine which patients should undergo radical nephroureterectomy. Other tools help post-operative decisions regarding the use of chemotherapy and planning follow-up sessions. The available pre-operative predictive tools and post-operative nomograms are discussed. A revision of the current classification of patients to low- and high-risk groups is recommended, to expand the number of patients benefiting from kidney-sparing surgeries. ABSTRACT: Diagnosis and risk stratification are cornerstones of therapeutic decisions in the management of patients with upper tract urothelial carcinoma (UTUC). Diagnostic modalities provide data that can be integrated, to provide nomograms and stratification tools to predict survival and adverse outcomes. This study reviews cytology, ureterorenoscopy and the novel tools and techniques used with it (including photodynamic diagnosis, narrow-band imaging, optical coherence tomography, and confocal laser endomicroscopy), and biopsy. Imaging modalities and novel biomarkers are discussed in another article. Patient- and tumor-related prognostic factors, their association with survival indices, and their roles in different scores and predictive tools are discussed. Patient-related factors include age, sex, ethnicity, tobacco consumption, surgical delay, sarcopenia, nutritional status, and several blood-based markers. Tumor-related prognosticators comprise stage, grade, presentation, location, multifocality, size, lymphovascular invasion, surgical margins, lymph node status, mutational landscape, architecture, histologic variants, and tumor-stroma ratio. The accuracy and validation of pre-operative predictive tools, which incorporate various prognosticators to predict the risk of muscle-invasive or non-organ confined disease, and help to decide on the surgery type (radical nephroureterectomy, or kidney-sparing procedures) are also investigated. Post-operative nomograms, which help decide on adjuvant chemotherapy and plan follow-up are explored. Finally, a revision of the current stratification of UTUC patients is endorsed.