Metastatic urothelial carcinoma: the drug is reimbursed, but the test is not
FGFR3 mutations are present in 20–60 per cent of cases: for this cancer too, molecular profiling is not yet covered by the National Health Service, pending the new LEAs list
Key points
Urothelial carcinoma is the fifth most commonly diagnosed cancer in Italia and accounts for 90 per cent of bladder cancers, with 28,000 new cases in 2024, 7,500 deaths in 2022 and 5,000 patients with metastatic disease.
Urothelial carcinoma, depending on the tumour stage, can be classified as: non-muscle-invasive (NMIBC), accounting for 75 per cent of cases at diagnosis, which is confined to the mucosa or lamina propria without invasion of the detrusor muscle; muscle-invasive (MIBC), accounting for 20 per cent of cases, which has invaded the muscular layer of the bladder wall; and metastatic disease, accounting for 5 per cent of cases.
The role of molecular profiling
For patients with metastatic urothelial carcinoma (MUC), both first-line and subsequent-line treatments have changed radically in recent years, thanks to new and more potent drugs. Furthermore, the introduction of genomic analysis has enabled the identification of certain molecular alterations, including those in the FGFR3 gene, which plays an important role in cell proliferation, angiogenesis and metastasis.
It is estimated that alterations (mutations or fusions) in FGFR3 are present in 20 per cent of MUC cases; however, their prevalence is considerably higher in carcinomas arising in the upper urinary tract, where it reaches 50–60 per cent. Since October 2025, the drug erdafitinib has been reimbursed by our National Health Service (SSN) for the treatment of patients with MUC who have FGFR3 alterations, whilst the profiling test to identify these alterations and determine eligibility for treatment is not currently included in the LEA list.
In particular, the detection of FGFR3 alterations requires the use of methods capable of both detecting mutations through DNA analysis and identifying gene fusions through RNA analysis. This assessment can be carried out using numerous commercially available NGS panels, generally comprising 50–52 genes, or by means of specific RT-PCR tests.
