Risk stratification for upper tract urinary carcinoma

Upper tract urinary carcinoma (UTUC) is a heterogeneous group of rare tumors. The aim of this article is to critically review current therapeutic strategies and to propose a change in the risk-stratification of the disease. A non-systematic review of the literature was performed using the Medline database with the search terms: “upper tract urothelial carcinoma” together with “prognostic factor”, “risk stratification”, “risk factor”, “recurrence”, “predictive tool”, “nomograms” and “treatment”. Preoperative risk factors can be viewed as patient-related risk factors (gender, age, ethnicity, body mass index, smoking status, or genetic factors), or tumor-related risk factors (stage, grade, size, architecture, multifocality, ureteric obstruction). Several biomarkers, available either in blood, urine, or the tumor itself have also been proposed. However, many of these prognostic factors lack accuracy and validation in predicting oncological outcomes, despite their use in predictive tools. After risk stratification, kidney-sparing strategies should be considered (endoscopic management and segmental ureterectomy) and could benefit from new diagnostic tools and technical improvements in in situ adjuvant endocavitary instillations. Radical nephroureterectomy remains the first choice therapy for high-grade disease and will probably be associated with other treatments in the future (lymphadenectomy, perioperative chemotherapy, or immunotherapy). In view of the major recent improvements in UTUC treatment strategies, a new classification should be proposed, including low-, intermediate-, high- and very high-risk disease. Subgroup analysis of good quality trials and better understanding of UTUC risk factors will help validate this new approach toward more personalized medicine.