Biomarkers of Bladder Cancer in Urine: Evaluation of Diagnostic and Prognostic Significance of Current and Potential Markers

The diagnosis of bladder cancer is generally made by cystoscopy and biopsy. Moreover, bladder cancer has a very high frequency of recurrence and therefore requires follow-up cystoscopy, along with urine cytology, as periodic surveillance to identify recurrence early. Cystoscopy is invasive and apt with complications like urine infection which sometimes lead to septicaemia with serious consequencies. Patient experience is most times not pleasant. Therefore, there needs to be a better way of surveillance for bladder cancer which is non-invasive and more acceptable to the patient experience. Consequently, urine biomarkers might be used to either supplement or supplant these tests. Urinary bladder carcinoma, the fourth most common cancer in men and ninth most common in women results in significant morbidity and mortality. Bladder cancer (urothelial carcinoma) typically presents as a tumour confined to the superficial mucosa of the bladder. The most common symptom of early bladder cancer is haematuria; however, urinary tract symptoms (i.e., urinary frequency, urgency and dysuria) may also occur. Most urologists follow the American Urological Association (AUA) guidelines for haematuria which recommend cystoscopic evaluation of all adults greater than 40 years old with microscopic haematuria and for those less than 40 years old with risk factors for developing bladder cancer. Confirmatory diagnosis of bladder cancer must by made by cystoscopic examination and biopsy which is considered to be the “gold standard.” At initial diagnosis, about 70 percent of patients have cancers confined to the epithelium or sub-epithelial connective tissue. Non-muscle invasive disease is usually treated with transurethral resection with or without intravesical therapy, depending on depth of invasion and tumour grade. However, there is a 75 percent incidence of recurrence in these patients with 10-15 percent progressing to muscle invasion over a five year period. Current follow-up protocols include flexible cystoscopy and urine cytology every three months for one to three years, every six months for an additional two to three years, and then annually, assuming no recurrence.