Comprehensive modalities of kidney-sparing treatment in a carefully selected cohort of localized high-risk upper tract urothelial carcinoma: A potential paradigm shift.

794 Background: This study aims to assess the efficacy and safety of comprehensive modalities of kidney-sparing treatment in a carefully selected cohort of patients with localized high-risk upper tract urothelial carcinoma (UTUC). Methods: This study was initiated in January 2019 and is ongoing. Selected localized high-risk UTUC patients, characterized by conditions such as solitary kidney, bilateral tumors, impending renal insufficiency or patient refusal/ineligibility for radical nephroureterectomy (RNU), were included. Systemic therapy regimens were tailored to patient characteristics, tumor pathology and biomarkers, and included platinum-based chemotherapy, Disitamab Vedotin, and immune checkpoint inhibitors (ICIs). After endoscopic biopsy and attempted laser ablation, patients received four cycles of systemic induction therapy, followed by maximal endoscopic laser ablation or segmental ureterectomy. Postoperatively, a one-year course of immunotherapy maintenance was administered. The co-primary endpoints were disease-free survival (DFS) and conversion-free survival (CFS). Secondary endpoints included metastasis-free survival (MFS), renal function changes, ureteral stricture and treatment safety. Results: 68 patients were enrolled, with a follow-up of 18 months. 54 patients underwent endoscopic thulium laser tumor ablation, while 14 underwent segmental ureterectomy. The induction therapy comprised Disitamab Vedotin for 32 patients, platinum-based chemotherapy for 9, and immunotherapy for 37. Urothelial tract recurrence was observed in 28 patients with a 1-yr DFS rate was 58.82%, who subsequently underwent repeat endoscopic laser ablation. Salvage RNU was performed in 9 patients, yielding a 1-yr CFS rate of 93.7% and a 2-yr CFS rate of 88.9%. No distal metastasis was reported. Postoperative renal function impairment was noted in 15 patients (22.06%). Mean eGFR improvements were observed at various time points: 3.15 ml/min/1.73m 2 at 1 months, 5.07 ml/min/1.73m 2 at 3 months, 2.41 ml/min/1.73m 2 at 6 months, and 3.97 ml/min/1.73m 2 at 12 months. Ureteral stricture on the affected side was a common complication, which was more likely to occur in patients who underwent 3 or more times of ureteroscopy (9/27). Notably, no grade 3 or higher systemic toxicities were observed. Conclusions: Preliminary findings indicate that our comprehensive modalities of kidney-sparing treatment demonstrated promising tumor control and satisfactory renal function preservation in a carefully selected cohort of localized high-risk UTUC. Its definite application strategy and value should be further evaluated in future clinical practice.