A systematic review of the diagnostic and prognostic value of urinary protein biomarkers in urothelial bladder cancer

For over 80 years, cystoscopy has remained the gold-standard for detecting tumours of the urinary bladder. Since bladder tumours have a tendency to recur and progress, many patients are subjected to repeated cystoscopies during long-term surveillance, with the procedure being both unpleasant for the patient and expensive for healthcare providers. The identification and validation of bladder tumour specific molecular markers in urine could enable tumour detection and reduce reliance on cystoscopy, and numerous classes of biomarkers have been studied. Proteins represent the most intensively studied class of biomolecule in this setting.
As an aid to researchers searching for better urinary biomarkers, we report a comprehensive systematic review of the literature and a searchable database of proteins that have been investigated to date. Our objective was to classify these proteins as: 1) those with robustly characterised sensitivity and specificity for bladder cancer detection; 2) those that show potential but further investigation is required; 3) those unlikely to warrant further investigation; and 4) those investigated as prognostic markers. This work should help to prioritise certain biomarkers for rigorous validation, whilst preventing wasted effort on proteins that have shown no association whatsoever with the disease, or only modest biomarker performance despite large-scale efforts at validation.