(UroToday.com) The 2026 European Association of Urology (EAU) annual meeting featured a session exploring the frontier of upper tract urothelial carcinoma and a presentation by Dr. Asaf Shvero discussing the efficacy and safety of padeliporfin VTP in the ENLIGHTED phase 3 study for low-grade upper tract urothelial carcinoma.
Padeliporfin VTP has demonstrated safety and efficacy for upper tract urothelial carcinoma treatment in a phase 1 study. Padeliporfin VTP is a combination product of a drug, padeliporfin administered IV, and an optical fiber coupled laser emitting near-infrared light endoluminally to upper tract urothelial carcinoma tumors:
Upon light activation, padeliporfin triggers a cascade of pathophysiological events that have a strong impact on tumor vasculature, and consists of the following consecutive steps:
At EAU 2026, Dr. Shvero and colleagues report the preliminary efficacy and safety outcomes of Padeliporfin VTP for treatment of low-grade upper tract urothelial carcinoma in ENLIGHTED.
This is an open-label phase 3 study conducted in the USA, the European Union, and Israel. The key inclusion criteria are (i) up to 2 biopsy-proven low-grade upper tract urothelial carcinoma with a tumor index ≤15 mm in the kidney (≤20 mm in the ureter), and (ii) absence of high-grade cytology. VTP is performed via retrograde upper tract endoscopy, under anesthetic and low-light conditions. Padeliporfin is injected IV, and an optical fiber, 20-40 mm diffuser length, is positioned in proximity to the tumor through the scope. After Padeliporfin injection, the laser is activated for 10 min. Patients are treated in two phases: induction and maintenance treatment phases. The induction treatment phase consists of 1-3 VTPs provided at 4-week intervals until achieving a complete response or treatment failure on the primary response evaluation visit. The primary endpoint is complete response on endoscopic evaluation and negative instrumental cytology at the time of primary response evaluation (28 ± 3 days post last treatment) during the induction treatment phase. Patients achieving complete response will proceed to maintenance treatment phases and be followed with endoscopic evaluation every 3 months, with VTP provided for recurrent tumors in the period up to 12 months. Patients completing the maintenance treatment phase will be followed for an additional 48 months for long-term outcomes:
A total of 100 patients are to be enrolled. As of October 19, 2025, 68 patients had been treated, and 61 completed the induction treatment phase. Response rates were: overall response 86.6%, complete response 71.6%, partial response 15.0%, disease recurrence 6.7%, progressive disease 5.0%, and stable disease 1.7%. The most frequent treatment-emerged adverse events were: hematuria 11.6%, flank pain 9.3%, nausea 5.6%, procedural pain 4.9%, abdominal pain 4.1%, vomiting 3.7%, dysuria 3.4%, fatigue 3.4%, UTI 2.6%, (all grade 1–2, median duration 5 days). There were 21 (7.7%) reported serious adverse events occurring in 16 patients (23.5%), and most were unrelated to VTP. One patient experienced a grade 3 serious adverse event (renal colic related solely to VTP), which resolved within 2 days.
Dr. Shvero concluded this presentation of updated safety and efficacy from the ENLIGHTED trial with the following concluding statements:
- Padeliporfin VTP has demonstrated a favorable safety and efficacy profile, with preliminary results consistent with prior clinical experience
- Recruitment for the ENLIGHTED phase 3 trial is ongoing
- The final study outcomes are expected to support regulatory approval of a novel, organ-preserving therapy for patients with low-grade upper tract urothelial carcinoma
Presented by: Asaf Shvero, MD, Sheba Medical Center, Ramat Gan, Israel
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2026 European Association of Urology (EAU) Annual Meeting, London, United Kingdom, Fri, Mar 13 – Mon, Mar 16, 2026.