<![CDATA[Upper tract urothelial carcinoma (UTUC) is an uncommon malignancy, accounting for only 5–10% of urothelial tumors, and often presents with invasive disease. Consequently, radical nephroureterectomy remains the standard treatment despite its substantial impact on renal function. Padeliporfin vascular‑targeted photodynamic therapy (VTP) is a novel kidney‑sparing modality in which intravenously administered padeliporfin is activated by endoluminal near‑infrared laser, selectively occlude tumor microvasculature and inducing coagulative necrosis while preserving surrounding tissues. This review synthesizes evidence from a Phase I study and the Phase III ENLIGHTED trial involving adults with low‑grade, non–muscle‑invasive UTUC suitable for kidney-sparing management, focusing on complete response (CR), durability of response, renal preservation, and safety outcomes. A search of PubMed, the Cochrane Library, and Web of Science identified seven reports arising from these two single‑arm study programs. In the Phase I trial, which predominantly included patients with residual or recurrent UTUC following unsuccessful endoscopic treatment, the 30‑day CR rate was 50%,, increasing to 68% after retreatment of partial responders, with an overall response rate of 94% and preservation of both renal function and kidneys at 6 months. In the ENLIGHTED trial, which enrolled patients with one or two small, biopsy‑confirmed low‑grade lesions, padeliporfin VTP achieved a CR rate of 73% at first assessment, overall response rates exceeding 86%, and local recurrence rates ranging from 3.2 to 10.8%. Among complete responders, 88% maintained CR for at least 12 months, and the median duration of response was not reached after more than 23.9 months of follow-up. Adverse events were predominantly transient Grade 1–2 urinary or flank symptoms; Grade 3 events were infrequent and short-lived, and no phototoxicity or ureteral strictures were reported. Padeliporfin VTP appears to be a promising kidney‑sparing treatment for selected patients with low‑grade UTUC, although confirmation in randomized controlled trials is needed. Keywords: Padeliporfin, Photodynamic Therapy, Upper Tract Urothelial Carcinoma, Kidney-Sparing Surgery, Endoscopic Ablation]]>
