 Previous publications from this Urology Department have introduced the idea of a non-invasive, molecular-based assay for the detection and monitoring of bladder cancer Levesque et al. 1993; Fitzgerald et al. 1995. At the time of publication there was limited knowledge of molecular changes underlying the different clinical pathways outlined above and our assay was based on one gene c-H-ras-1. In the last few years, it has become clear that activation events associated with FGFR-3 can be found associated with 40-60 of low-grade, low-stage bladder tumors whilst p53 mutations are linked to a more aggressive phenotype progressing via the CIS pathway. Mutations found in the c-H-ras-1 gene can straddle both of these groups. We propose to assess the use of a multiple mutation-based assay, using DNA from exfoliated cells in the urine of patients, to establish the sensitivity and specificity in tumor detection compared to cystoscopy and cytology. In addition, we propose to isolate free-DNA for use in molecular assays. The remaining urine will be stored to evaluate biomarkers for the detection of tumor presence or progression using protein-based analyses. 