Abstract
Upper tract urothelial carcinoma (UTUC) is a rare but aggressive malignancy characterized by high rates of muscle-invasive and non-organ-confined disease at diagnosis, substantial postoperative renal function decline, and frequent intravesical recurrence. These clinical features complicate the use of cisplatin-based chemotherapy and limit the development of robust, disease-specific evidence. Most perioperative recommendations remain extrapolated from bladder cancer, and considerable uncertainty persists regarding the optimal integration of chemotherapy, immunotherapy, and emerging biomarkers. This review aims to synthesize contemporary evidence on neoadjuvant and adjuvant systemic therapy in UTUC, identify persistent gaps in clinical practice, and outline future research priorities in the era of biomarker-driven treatment.