Modern management of locally advanced urothelial carcinoma of the upper urinary tract.

purposeUpper tract urothelial carcinoma (UTUC) is a rare malignancy arising from the renal pelvis or ureter and is often diagnosed at an advanced stage. Prognosis depends strongly on tumor stage and grade, but remains poorer than that of bladder urothelial carcinoma.

methodsThis review article summarizes current evidence on the management of locally advanced but resectable UTUC, focusing on perioperative systemic therapy, clinical guideline recommendations, and emerging therapeutic strategies.

resultsIn high risk cases, radical nephroureterectomy (RNU) with bladder cuff excision is the surgical state of the art. To reduce relapse rates, perioperative systemic therapy is gaining increasing importance. Neoadjuvant platinum-based chemotherapy (+/- durvalumab) has shown promising rates of pathological downstaging, however, high level evidence is still lacking. In contrast, evidence for adjuvant therapy is stronger. Adjuvant platinum-based chemotherapy should be offered to patients with pT2-pT4 or pN+ disease within 90 days after RNU. Immune checkpoint inhibitors show activity in perioperative settings, but potential benefits in UTUC subgroups remain unclear. There are ongoing trials combining immunotherapy, chemotherapy, or targeted agents. Molecular profiling and novel strategies, such as mRNA vaccines and antibody-drug conjugates, may enable more personalized approaches and reshape the therapeutic landscape of UTUC.

conclusionManagement of locally advanced but resectable UTUC is evolving rapidly, driven by advances in perioperative systemic therapies and a growing understanding of the disease's molecular biology. However, prognosis remains poor, underscoring the need to further improve treatment options.