Upper Tract Urothelial Carcinoma (UTUC) accounts for approximately 5–10% of urothelial cancers and develops in the renal pelvis or ureter. These tumours respond poorly to systemic chemotherapy and often recur, making radical nephroureterectomy or partial bladder resection the current standard of care. However, surgery is frequently not feasible or can severely reduce patient quality of life due to complications. UTUC patients are typically older, with an average age of 73 at diagnosis, and often have co-morbidities that compound health risks. Up to 50% of patients already have impaired renal function, and surgery can worsen this, limiting future use of cisplatin-based chemotherapy for metastatic disease. Currently, there are few effective systemic treatments for UTUC, leaving clinicians unable to treat patients who are ineligible for surgery or for whom surgery would be excessively harmful. Even when treatment options exist, morbidity and toxicity remain high, leading to complications, reduced quality of life, and diminished future treatment possibilities due to renal failure.
In 2019, EU inpatient care spending represented about 3.1% of GDP (€432.52 billion), while overall health spending was 7% (€983 billion). Current UTUC treatment protocols often require multiple hospitalizations. A retrospective study reported excess costs of $252,272 (~€220,840) per patient over five years, largely due to the high incidence of end-stage renal failure following surgery. Most low-grade UTUC patients undergo radical nephroureterectomy within a year of diagnosis, underscoring the need for alternatives.
Padeliporfin VTP (Vascular Targeted Photodynamic Therapy) offers a novel, minimally invasive oncology platform for treating solid tumours. It combines an intravenous drug, Padeliporfin-dipotassium, with a proprietary laser and fibre device for localized, non-thermal light delivery. Padeliporfin is derived from bacteriochlorophyll and remains inactive until illuminated. After administration, it binds to serum albumin and circulates for a short time before elimination. When activated by laser light, it reacts with oxygen to produce radicals that block tumour blood vessels, causing tumour necrosis within hours. This process triggers immunogenic cell death and immune activation, enhancing efficacy while sparing healthy tissue. The treatment is repeatable in the same area, preserves the organ, and minimizes side effects. The innovation consists of two elements: the drug and the device enabling precise photoactivation. The therapy eliminates tumours efficiently, preserves renal function, and avoids surgical morbidity. It also activates the immune system, improving outcomes beyond local control. The technology has reached TRL7 and has been validated in operational settings, including EMA approval for low-grade prostate cancer and a Ph1 trial for low-grade UTUC. Current efforts focus on qualifying and validating drug efficacy in a Phase 3 pivotal study under the EIC framework, preparing for market entry after trial completion and regulatory approval.
