(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Annual Symposium held in San Francisco, CA between February 13–15, 2025 was host to a urothelial carcinoma poster session. Dr. Jianjun Ye presented the results of a pilot study combining endoscopic thulium laser ablation with perioperative disitamab vedotin and immune checkpoint inhibitors as a kidney-sparing approach for select patients with localized, high-risk upper tract urothelial carcinoma (UTUC).
Radical nephroureterectomy (RNU) is the standard-of-care treatment for localized high-risk 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 multimodal kidney-sparing approach, comprising endoscopic Thulium laser ablation plus perioperative systemic therapy (Disitamab vedotin [DV] and immune checkpoint inhibitors [ICIs]), in a carefully selected cohort of patients with localized, high-risk UTUC.
This ongoing study, initiated in November 2021 at West China Hospital of Sichuan University, included select patients with localized UTUC (≤cT2N0M0) and who had ‘complicating’ conditions precluding an RNU, such as a solitary kidney, bilateral tumors, impending/pre-existing renal insufficiency, and refusal/ineligibility for RNU.
Additional eligibility criteria included:
- Tumor diameter <20mm
- Expected survival time > 2years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Estimated glomerular filtration rate (eGFR) ≥ 15 ml/min
- Adequate hepatic and hematological function.
Exclusion criteria comprised HER2 expression by immunohistochemistry (IHC), previous history of radical cystectomy, ureteral stricture, or other conditions precluding ureteroscopy.
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.
The co-primary endpoints were 1-year disease-free survival and conversion-free survival. Secondary endpoints included:
- Overall survival
- Cancer specific survival
- Metastasis-free survival
- Intravesical recurrence-free survival
- Renal function benefits
- TRAEs
Between June 2021 and August 2024, 33 patients with localized UTUC were included. The median patient age was 73 years. 15% had a solitary kidney. 9% had bilateral UTUC. 70% had CKD stage 3 or worse disease. The median tumor size was 1.87 cm, and the location was the ureter in 55% and renal pelvis in 45%.
The median follow-up was 23 months (IQR: 16–28 months). 19 local recurrences were observed in 12 patients and the 1-year DFS rate was 69.7%. HER2 status was a significant predictor of local recurrence odds (OR: 0.15; 95% CI: 0.03–0.91). Salvage RNU was performed in two patients, yielding a 1-yr CFS rate was 93.75%.
Post-operative renal function impairment was noted in 6 patients (18.8%). Mean eGFR (ml/min/1.73m2) improvements were noted pre-operatively with a 3.2 unit improvement at 1 month, 5.1 at 3 months, 2.4 at 6 months, and 4.0 at 12 months.
Eleven patients (33.3%) developed ureteral strictures that required management with either double J ureteral stent placement or extra endoscopic management. No grade ≥3 systemic toxicities were observed.
Dr. Ye concluded that these preliminary findings suggest that the combination of endoscopic Thulium laser ablation combined with perioperative systemic therapy (DV and ICIs) demonstrates promising efficacy and manageable safety in select patients with localized, high-risk UTUC. These results provide a solid foundation for the ongoing phase II trial (WUTSUP-03) and suggest a novel treatment approach to the management of UTUC who are poor candidates for an RNU.
Presented by: Jianjun Ye, MD, Department of Urology and Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.