Current status of genetic urinary biomarkers for surveillance of non-muscle invasive bladder cancer: a systematic review

BACKGROUND: Genetic biomarkers are a promising and growing field in the management of bladder cancer in all stages. The aim of this paper is to understand the role of genetic urinary biomarkers in the follow up of patients with non muscle invasive bladder cancer where there is increasing evidence that they can play a role in avoiding invasive techniques. METHODS: Following PRISMA criteria, we have performed a systematic review. The search yielded 164 unique articles, of which 21 articles were included involving a total of 7261 patients. Sixteen of the articles were DNA based biomarkers, analyzing different methylations, microsatellite aberrations and gene mutations. Five articles studied the role of RNA based biomarkers, based on measuring levels of different combinations of mRNA. QUADAS2 critical evaluation of each paper has been reported. RESULTS: There are not randomized control trials comparing any biomarker with the gold standard follow-up, and the level of evidence is 2B in almost all the studies. Negative predictive value varies between 55 and 98.5%, being superior in RNA based biomarkers. CONCLUSIONS: Although cystoscopy and cytology are the gold standard for non muscle invasive bladder cancer surveillance, genetic urinary biomarkers are a promising tool to avoid invasive explorations to the patients with a safe profile of similar sensitivity and negative predictive value. The accuracy that genetic biomarkers can offer should be taken into account to modify the paradigm of surveillance in non muscle invasive bladder cancer patients, especially in high-risk ones where many invasive explorations are recommended and biomarkers experiment better results.