Urine DNA test may help predict BCG response in non-muscle invasive bladder cancer

A study published in Cell suggests that a simple urine test may help identify which people with bladder cancer are likely to benefit from BCG immunotherapy and those who will not. The new urine-based test can detect minimal residual bladder cancer after surgery and BCG treatment by analyzing tumour DNA in urine. The findings could mark a step toward more personalized treatment.

Approximately 70 to 75% of newly diagnosed bladder cancers are non-muscle invasive bladder cancer (NMIBC). Standard treatment for NMIBC typically involves surgical removal of tumours using a procedure called transurethral resection of bladder tumour (TURBT). For higher risk NMIBC, a person may receive Bacillus Calmette-Guérin (BCG) immunotherapy.

Although effective, BCG therapy can be poorly tolerated and it is difficult to predict how people may respond. There is currently no reliable way to predict who truly needs additional therapy after surgery, or who will still experience recurrence despite receiving it. This uncertainty can expose patients to side effects, contribute to treatment shortages, and delay more effective interventions for those whose cancer persists.

The test can distinguish between those likely to be cured by surgery alone, those who could benefit from BCG immunotherapy, and those who do not respond and are at high risk of recurrence. Participants with detectable tumour DNA after completing BCG were highly likely to experience cancer recurrence, while those whose tumour DNA cleared had excellent outcomes. These tests may offer a noninvasive way to monitor disease at a molecular level, and could detect signs of remaining cancer after treatment for NMIBC.

The research explores the potential of urine-based liquid biopsies, which detect tumour DNA fragments shed into bodily fluids. In bladder cancer, urine is particularly useful because it comes into direct contact with tumour cells in the bladder lining. The method was designed to focus on mutations that are unique to tumor cells and not found in non-cancer cells affected by the field effect.

The researchers identified an important complication in that healthy bladder tissue can accumulate cancer-like genetic alterations with age. The researchers describe this phenomenon as clonal cystopoiesis. Clonal cystopoiesis poses a major challenge for urine DNA-based tests because these assays detect mutations without distinguishing their source, and mutations arising from normal cells could be misinterpreted as tumor-derived, leading to false-positive results.