"Bladder cancer is a recurrent and very prevalent cancer and it generates the highest cost per patient in Europe. New genomic methods have allowed identifying new markers with potential clinical application. However, due to the use of single-marker assays and poor study design, none of these markers has made it to the clinic. FGFR3 and PIK3CA mutations, expression profiles, and microsatellite alterations in tumor tissue and urine, as well as polymorphisms in immune response genes, are very promising biomarkers that predict a tumor being present in the bladder and its likelihood of progression to invade the muscle. Here, we propose to combine the best markers of bladder cancer outcome in a prospective multicenter validation study in Spain, the Netherlands, Sweden and Denmark as genetic predictors. Pre-validation of markers has been or will be made utilizing the world’s largest bladder cancer biobank (60,000 samples from 2500 patients). To achieve enough power to rapidly generate conclusive results, 2000 patients will consecutively be enrolled, and subjected to analysis, as well as follow-up for 2-4 years. The approach is a pre-defined, standard operating procedure based, prospective study with fixed end-points and testing relatively few independent variables on tumor tissue, urine and blood. To obtain a seamless introduction into the clinic we will use a mathematical approach in which the best markers are weighted based on disease models and nomogram construction, leading to a risk score applied to each patient at each visit. The team has a very strong track record in bladder cancer research, micro-array application, nomogram construction, and bio-banking. The validated biomarkers will lead to specific recommendations for changes in patient management based on the risk scores. We estimate saving of more than 40 mill Euros annually based on a reduced frequency of cystoscopies, as well as an increased survival and a better quality of life for the patients."