Urine tests for bladder cancer (cytology, FISH, RNA and methylation)

What they measure. Bladder tumours shed cells and nucleic acids straight into urine, so urine is the natural sample. The oldest test is cytology, a pathologist looking for malignant cells, which is very specific for high-grade cancer but misses most low-grade tumours. Protein tests (NMP22, BTA) are cheap but give false positives with infection, stones and haematuria. UroVysion uses fluorescence in situ hybridisation to spot the chromosome gains and 9p21 loss typical of bladder cancer. Cxbladder measures five messenger RNAs; Xpert Bladder Cancer measures five others on a cartridge; Bladder EpiCheck reads a panel of methylation markers; and research tests sequence urine DNA for the FGFR3, TERT promoter and other mutations found in most tumours.

Who should have them. Two settings. In the work-up of blood in the urine, a very sensitive test with a high negative predictive value can let a patient with low risk avoid cystoscopy. In follow-up of treated non-muscle-invasive bladder cancer, where patients face cystoscopy every three to twelve months for years, a negative urine test can lengthen the interval or replace alternate examinations. European Association of Urology guidelines currently allow urine tests to complement cystoscopy and cytology but not to replace them, and the FDA-approved tests (UroVysion, NMP22, BTA) are for monitoring known cancer and for haematuria work-up alongside cystoscopy.

What changes. A positive test prompts cystoscopy, upper tract imaging and, if nothing is seen, a closer look with blue-light cystoscopy or repeat testing. A negative high-sensitivity test in a low-risk patient can defer cystoscopy, which is the cost and comfort argument. Costs range from a few pounds for cytology to a few hundred for RNA or methylation tests; cytology and UroVysion are widely available, the newer tests through their makers' laboratories. Randomised trials of replacing surveillance cystoscopy with urine testing are in progress.