The clinical relevance of FGFR3 testing in bladder cancer

5 Aug 2024

Up to 20% of patients with advanced urothelial carcinoma may have FGFR alterations, with FGFR3 mutations and fusions being predominant in bladder and upper tract urothelial tumours.^1,2

The prevalence of FGFR3 mutations and fusions is approximately 80% in non-muscle-invasive bladder cancer (NMIBC) patients, compared to 20% in muscle-invasive bladder cancer (MIBC) patients.³ To ensure eligible patients receive targeted therapies specific to FGFR3 alterations, accurate testing of FGFR3 gene is essential.

FGFR3 alterations play a pivotal role in the development and progression of bladder cancer. Its frequent mutations and fusions make it a key biomarker for targeted therapy in bladder cancer patients.

FGFR inhibitors have shown efficacy in treating FGFR3-altered urothelial cancer⁴, but identifying patients who will benefit most from FGFR3-targeted therapies requires reliable and comprehensive molecular testing.

Diagnosing FGFR3 in bladder cancer

Gene mutations and fusions of FGFR3 are important for diagnosing bladder cancer. As such, RNA samples may be required. Tissue biopsy (TURBT - transurethral resection of urothelial tumour) is the gold standard for FGFR3 testing in metastatic urothelial carcinoma.⁵ However, TURBT can result in heterogeneous samples, thus impacting the tissue quality available for biomarker testing. If fresh biopsies are not feasible, tumor tissues archived via formalin fixed and paraffin embedded (FFPE), using fresh or flash frozen methods from diagnosis can be used.

Additionally, urine testing (urine cytology and tissue marker tests) has the potential to assist in clinical decision-making due to its ease of sampling, potentially reducing the need for invasive procedures.

There are 3 major diagnostic pitfalls that labs should consider when testing for FGFR3 in bladder cancer:

Test selection: The choice of test may depend on the clinical context, available resources, and specific FGFR3 alterations of interest. For instance, NGS provides comprehensive data but may not be necessary for detecting a known single mutation, where RT-PCR could suffice.
Sample quality: The accuracy of FGFR3 testing depends on the quality of the sample. Adequate tumor content in tissue biopsies or sufficient DNA/RNA quantity and quality from urine samples are essential.
Interpretation of results: Positive results for FGFR3 genetic alterations can help in prognostication and selecting patients for FGFR-targeted therapies. Negative results, particularly from highly sensitive methods like NGS or RT-PCR, mean a patient is not eligible for the targeted therapy.

Learn more in our upcoming Lab Talk

In September, Diaceutics will host a Lab Talk with Dr. Mike Hubank, Scientific Director, Royal Marsden Hospital, London entitled "FGFR3 testing in bladder cancer" discussing the clinical utility of FGFR3 alterations in bladder cancer patients, the patient diagnostic journey and technical challenges when testing for FGFR3 in bladder cancer.

^References:

^{1. Helsten T et al. Clin Cancer Res 2016;22(1):259–267. 2. Necchi A et al. Eur Urol Focus 2019;5(4):689–692. 3. Wang Z et al. npj Precis Onc 2023;7(70). 4. Benjamin DJ et al. Front Immunol. 2023;14:1258388. 5. Mazzucchelli R et al. Front Surg. 2021 Dec 2;8:754741.}

^{Approval code: EM-162587}