|Project outline
BLADE – Bladder Cancer Detection using Metabolomic Evaluation of Urine and Blood
Objective:
Development and Evaluation of a metabolite constellation for the diagnosis of bladder cancer in patients with persistent microhaematuria.
Study Manager Clinical Development, numares AG
Urinary bladder cancer (BCa) is a malignant tumour that usually develops in the mucous membrane (urothelial carcinoma) of the bladder. The symptoms are relatively unspecific. One of the earliest cardinal symptoms of BCa is microscopically detectable haematuria, so-called microhaematuria, [1]. However, microhaematuria commonly has benign causes, such as infection, benign prostate enlargement or kidney stones, and is caused by malignant tumors only in 2 - 5 % of cases [2]. The key issue in the management of microhaematuria is therefore to reliable detect rare malignant bladder tumors among common benign diseases [3]. Since urinary cytology and current available urinary markers lack sufficient clinical reliability, cystoscopy in combination with biopsy and trans-urethral resection of the bladder (TURB) are considered the gold standard for the diagnosis of bladder tumors [4,5] and frequently used for urologic evaluation of persistent microhaematuria. However, these examinations are invasive, expensive [1] and unnecessary for the majority of patients with microhaematuria. Those would greatly benefit from a non-invasive, metabolomics-based test that reliable detects bladder cancer in microhaematuria and – when used as triage to cystoscopy – would help reduce unnecessary diagnostic procedures.
Study design:
BLADE is a multicentre, two-step adaptive prospective observational study
Material:
Urine and serum samples from patients scheduled for cystoscopy or TURB due to persistent microhaematuria
Reference standard:
Bladder cystoscopy in combination with biopsy or trans-urethral resection of the bladder (TURB)
Approach:
Over the past 20 years, a variety of molecular markers has been proposed for the detection of BCa in patients with persistent microhaematuria to meet the medical need for a triage test to reduce unnecessary cystoscopies [3]. None of the new markers is currently well established in clinical routine. Transferred to a heterogeneous patient population with multiple causes of microhaematuria, only a pattern with multiple markers is likely to provide sufficient diagnostic accuracy to exclude bladder cancer as a cause of microhaematuria. With the AXINON® platform, numares has a reliable, fast and flexible analysis system for the simultaneous acquisition of several hundred metabolites in a single analytical step. The metabolomics approach will now provide initial insights into the processes and metabolic changes in in bladder cancer. This will be the basis for developing a non-invasive, metabolomics-based test for bladder detection in microhaematuria.
Success:
In-house preliminary work identified a metabolite constellation that allows detection of BCa by NMR analysis of urine.
References:
1. Schwartz, G.L., Proper evaluation of asymptomatic microscopic hematuria in the era of evidence-based medicine--progress is being made. Mayo Clin Proc, 2013. 88(2): p. 123-5.
2. Elias, K., et al., High-risk patients with hematuria are not evaluated according to guideline recommendations. Cancer, 2010. 116(12): p. 2954-9.
3. Schmitz-Drager, B.J., et al., Immunocytology in the assessment of patients with asymptomatic hematuria. World J Urol, 2008. 26(1): p. 31-7.
4. Babjuk, M., et al. EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder. Eur Urol. 2017 Mar;71(3):447-461
5. Davis, R., et al. Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline. J Urol. 2012. 188:2473-81
numares’ products are not yet available for sale within the United States; they have not yet been approved or cleared by the U.S. Food and Drug Administration.
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