2018P - Nephron-sparing surgery combined with perioperative systemic therapy in select high-risk upper tract urothelial carcinoma (UTUC) Patients: A pilot study for a prospective phase II trial

Background

The standard treatment for localized high-risk upper tract urothelial carcinoma (LHR-UTUC) is radical nephroureterectomy (RNU). However, reduced tolerability and risk of renal insufficiency highlight the need for altered strategies that preserve functional nephron. This study aims to assess the efficacy and safety of a kidney-sparing surgery, with systemic therapy, in LHR-UTUC patients.

Methods

This study started in January 2019 and is ongoing. LHR-UTUC patients with solitary kidney, bilateral tumors, renal function insufficiency or ineligiblity for RNU, were included. Systemic therapy regimens were tailored based on pathology and biomarkers, including platinum-based chemotherapy (PC), Disitamab Vedotin (DV) and immune checkpoint inhibitors (ICIs). After endoscopic biopsy and laser ablation, patients received four cycles of systemic induction therapy, followed by endoscopic laser ablation or segmental ureterectomy. A 1-year course of immunotherapy was administered. The primary endpoints were metastasis and clinical complete response (cCR). Secondary endpoints were progression, renal function (estimated glomerular filtration rate, eGFR ml/min/1.73m²), and side effects.

Results

36 patients were enrolled. 30 underwent endoscopic thulium laser tumor ablation, 6 underwent segmental ureterectomy. The induction therapy comprised DV for 13 patients, PC for 3, and ICIs for 16. Recurrence was observed in 8 patients, repeat endoscopic laser ablation was performed. Salvage RNU was performed in 5 patients. Of those not achieving cCR, 2 underwent salvage RNU within 3 months, while the remaining 3 maintained their nephrons. Postoperative renal function impairment was noted in 5 patients, with a median pre-surgery eGFR of 61.54 (20.26, 113.77) and a median post-surgery eGFR of 56.28 (23.25, 117.04). No grade 3 or higher systemic toxicities were observed.

Conclusions

Preliminary findings indicate that our strategy demonstrated promising tumor control and satisfied renal function preservation. These results provide a foundation for further investigating nephron-sparing therapy in a select group of patients with localized high-risk UTUC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Ethics Committee on Biomedical Research, West China Hospital of Sichuan University.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.