JU INSIGHT Phase I Trial of Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma

By: Wesley Yip, MD, Memorial Sloan Kettering Cancer Center, New York, New York; Daniel D. Sjoberg, PhD, Memorial Sloan Kettering Cancer Center, New York, New York; Lucas M. Nogueira, MD, Memorial Sloan Kettering Cancer Center, New York, New York; Andrew T. Tracey, MD, Memorial Sloan Kettering Cancer Center, New York, New York; Ricardo G. Alvim, MD, Memorial Sloan Kettering Cancer Center, New York, New York; Peter A. Reisz, MD, Memorial Sloan Kettering Cancer Center, New York, New York; Quinlan Demac, BS, Memorial Sloan Kettering Cancer Center, New York, New York; Nicole E. Benfante, BS, Memorial Sloan Kettering Cancer Center, New York, New York; Rand W. Vanden Berg, MD, Memorial Sloan Kettering Cancer Center, New York, New York; Kwanghee Kim, PhD, Memorial Sloan Kettering Cancer Center, New York, New York; Hikmat Al-Ahmadie, MD, Memorial Sloan Kettering Cancer Center, New York, New York; Oscar Lin, MD, Memorial Sloan Kettering Cancer Center, New York, New York; Bernard H. Bochner, MD, Memorial Sloan Kettering Cancer Center, New York, New York; Guido Dalbagni, MD, Memorial Sloan Kettering Cancer Center, New York, New York; S. Machele Donat, MD, Memorial Sloan Kettering Cancer Center, New York, New York; Eugene J. Pietzak, MD, Memorial Sloan Kettering Cancer Center, New York, New York; A. Ari Hakimi, MD, Memorial Sloan Kettering Cancer Center, New York, New York; David B. Solit, MD, Memorial Sloan Kettering Cancer Center, New York, New York; Avigdor Scherz, PhD, Weizmann Institute of Science, Rehovot, Israel; Dean F. Bajorin, MD, Memorial Sloan Kettering Cancer Center, New York, New York; Jonathan A. Coleman, MD, Memorial Sloan Kettering Cancer Center, New York, New York | Posted on: 18 May 2023

Yip W, Sjoberg DD, Nogueira LM, et al. Final results of a phase I trial of WST-11 (TOOKAD Soluble) vascular-targeted photodynamic therapy for upper tract urothelial carcinoma. J Urol. 2023;209(5):863-871.

Study Need and Importance

Radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) is associated with significant morbidity and risk of renal dysfunction, and so organ-sparing strategies are highly compelling when appropriate. Existing endoscopic management techniques with laser ablation or electrocautery fulguration often require repeated procedures with increased cumulative risks of serious complications and high rates of recurrence. Thus, there is compelling rationale to improve upon the current management strategies for patients with UTUC. Vascular-targeted photodynamic therapy (VTP), which causes nonthermal tissue destruction, has demonstrated efficacy in other tumor types and preclinical models, with potential for use as an endoluminal treatment in the urinary tract.

What We Found

This trial demonstrates the safety and preliminary efficacy of VTP for UTUC, with an initial 30-day treatment response rate of 94% (50% complete, 44% partial; see Figure). The trial results have established the supporting evidence for a recently initiated multi-center Phase 3 trial (ENLIGHTED), evaluating the efficacy of VTP in low-grade UTUC, as well as a future trial for high-grade UTUC.

Figure. Endoscopic appearance of tumor before and after 1 vascular-targeted photodynamic therapy treatment.

Limitations

Our study is limited by the small sample size, follow-up duration, and broad patient selection criteria, which did not limit tumor size or grade. The majority of patients in this trial had previously failed other local ablative therapies as well.

Interpretation for Patient Care

The results of this trial suggest that VTP may be a safe alternative to current kidney-sparing treatment options in select patients with both low- and high-grade UTUC, which warrants further study in a larger prospective trial setting.