RT-PCR assay for the diagnosis and surveillance of bladder cancer from urine
It addresses the need for a cost-effective non-invasive assay for diagnosis and surveillance of bladder cancer. It is based on a clinically validated signature of ten differentially-expressed genes and displays superior performance (sensitivity 80%; specificity 94%; AUC 0.91) to other molecular markers in the market. The validation study also demonstrated the excellent performance of additional of 2, 5 and 12-gene panels.
Bladder cancer is among the five most common malignancies worldwide being responsible for 3% of all cancer deaths in males and 1% in females. If detected early, 5-year survival is high (94%), but >70% of diagnosed patients will relapse within this period, with 20% progressing to muscle invasive cancer (T2 or higher). High prevalence, survival and relapse rates combine to make BC one of the most expensive cancers to treat and monitor.
The gold standard diagnostic tool is combined cystoscopy and cytology which is costly and highly invasive requiring transurethral access and presenting the risk of important complications and discomfort to patients. Because clinical symptoms are not useful in predicting progression, surveillance requires frequent cystoscopies, on average in excess of 13 per patient following initial diagnosis and treatment.
A clear opportunity exists to replace suveillance, and eventually initail examinations, with a cost-effective and non-invasive procedure.
Format and clinical performance
The current assay is based on a validated panel of 10 differentially expressed genes employing RT-qPCR on spontaneous urine samples [1-4].
Clinical results on 525 patients after a prospective multinational validation demonstrated that our single non-invasive test yields 80% sensitivity and 94% specificity vs. 80% sensitivity and 90% specificity for combined invasive and costlier cystoscopy and cytology . This performance is superior to that of competing biomarkers in the market (NMP22, Alere or BTA Stat, Polymedco) as well as being significantly cheaper than FISH-based tests (UroVysion, Abbott).
Biofina Diagnostics holds the commercial exploitation rights of the patent families protecting the diagnostic method. The first one has been granted in the EU, USA, Canada and Japan. Additional gene-signatures have been claimed in a new EU patent application filed in January 2013 that entered the PCT phase in January 2014 and Regional phases in August 2015 (See IP status below).
Biofina Diagnostics S.L. is currently seeking a licensing/distribution partner with capacity to support the company in taking this assay into the market.
- Mengual L, Burset M, Ars E, Ribal MJ, Lozano JJ, Miñana B, Sumoy L, Alcaraz A. Partially degraded RNA from bladder washing is a suitable sample for studying gene expression profiles in bladder cancer. Eur Urol 2006, 50(6);1347-56. PMID: 16815626.
- Mengual L, Burset M, Marin-Aguilera M, Ribal MJ, Alcaraz A. Multiplex preamplification of specific cDNA targets prior to gene expression analysis by TaqMan Arrays. BMC Research Notes 2008, 1:21. PMID: 18710479.
- Mengual L, Burset M, Ars E, Lozano JJ, Villavicencio H, Ribal MJ, Alcaraz A. Expression profiling of bladder cancer by DNA microarrays allows the identification of non-invasive diagnostic markers. J Urol 182:741-8,2009. PMID: 19539325.
- Mengual L, Burset M, Ribal MJ, Ars E, Marín-Aguilera M, Fernández M, Ingelmo-Torres M, Villavicencio H, Alcaraz A. Gene expression signature in urine for diagnosis and aggressiveness assessment of bladder urothelial carcinoma. Clin Can Res. 2010 May 1;16(9):2624-33. PMID: 20406841.
- Mengual L, Ribal MJ, Lozano JJ, Ingelmo-Torres M, Burset M, Fernandez PL, Alcaraz A. Validation Study of a Noninvasive Urine Test for Diagnosis and Prognosis Assessment of Bladder Cancer: Evidence for Improved Models. J Urol. Vol. 191, 1-9, January 2014.
- Family PCT/ES/2007/000330, priority 20/03/2007: Protects the method, use and kit containing specific genetic signatures for the diagnosis and/or prognosis of bladder cancer. The patent has been granted in the EU, USA, Canada and Japan. The patent is pending in India.
- Family PCT/EP2014/051939, priority 31/01/2013: Protects new genetic signatures with higher diagnostic performance. Applied to in the European Patent Office (EPO), the patent was extended to PCT phase on 31/01/2014. The entrance in Regional Phase took place in August 2015 in the following territories: Europe, EEUU, Canada, China, Australia and Israel.