Kidney-sparing approach for selected localized high-risk upper tract urothelial carcinoma: A pilot study combining endoscopic thulium laser ablation with perioperative disitamab vedotin and immune checkpoint inhibitors.

Abstract

791 Background: Radical nephroureterectomy (RNU) is the standard treatment for localized high-risk upper tract urothelial carcinoma (UTUC). However, the predominance of UTUC in elderly populations with significant comorbidities necessitates alternative treatment strategies that prioritize functional nephron preservation. This pilot study aims to assess the efficacy and safety of a comprehensive modality of kidney-sparing approach, comprising endoscopic Thulium laser ablation and perioperative systemic therapy (Disitamab vedotin [DV] and immune checkpoint inhibitors [ICIs]), in a carefully selected cohort of localized high-risk UTUC. Methods: This ongoing study, initiated in November 2021 at West China Hospital of Sichuan University, included selected patients with localized UTUC patients (cT≤2N0M0) characterized by conditions such as solitary kidney, bilateral tumors, impending/already renal insufficiency and individual refusal/ineligibility for RNU. The treatment protocol consisted of endoscopic biopsy and initial laser ablation, followed by 3-4 cycles of DV and ICIs administered every three weeks as induction therapy. Subsequently, patients underwent maximal endoscopic laser ablation. Those exhibiting efficient response received a 6-month course of DV and a 12-month course of ICIs as maintenance therapy. Co-primary endpoints were 1-yr disease-free survival (DFS) and conversion-free survival (CFS). Secondary endpoints included clinical complete response (cCR) rate, renal function benefits, and treatment safety. Results: Thirty-two patients were enrolled, with a median follow-up of 15 months. The majority of patients (26/32, 81.25%) were diagnosed with HER2-positive in biopsy-related IHC, including 3 cases of HER2 3+ and 23 cases of HER2 2+. During the follow-up, 17 local recurrences were observed in 10 patients and the 1-yr DFS rate was 68.75%. HER2 status was a significant predictive factor for local recurrence (OR, 0.15; 95% CI, 0.03, 0.91). Salvage RNU was performed in 2 patients, yielding a 1-yr CFS rate was 93.75%. The cCR rate is 78.13% (25/32). Postoperative renal function impairment was noted in 6 patients (18.75%). Mean eGFR improvements (ml/min/1.73m2) were observed with 3.15 at 1 month, 5.07 at 3 months, 2.41 at 6 months, and 3.97 at 12 months. Notably, no grade 3 or higher systemic toxicities were observed. Conclusions: Preliminary findings indicate that the combination of endoscopic Thulium laser ablation with perioperative systemic therapy (DV and ICIs) demonstrated promising efficacy and manageable safety in selected patients with localized high-risk UTUC. These results provide a solid foundation for the ongoing phase 2 trial (WUTSUP-03) and suggest a potential paradigm shift in the management of this challenging patient population.