Non-muscle invasive bladder cancer (NMIBC) can be treated with the BCG vaccine, an old vaccine for tuberculosis. But not all patients respond to this unique immunotherapy and there is no way to predict who these responders might be. Analysis of tumor DNA in urine (utDNA) from patients could help but liquid biopsies are confounded by the “field effect”, or mutations in noncancerous cells around the tumor. Researchers co-led by Ludwig Stanford’s Max Diehn and Ash Alizadeh with a Stanford colleague reported in a Cell paper in January that such mutations increase with age—as does the incidence of bladder cancer. They also described a method to identify and remove field effect mutations in utDNA analysis to improve the accuracy of such prediction in patients who have undergone surgery and are being considered for adjuvant BCG therapy. Analyzing 261 samples from NMIBC patients who received BCG following surgery, Max and his colleagues identified three classes of patients: nonresponders, BCG responders and surgery responders. They found that BCG responders show evidence of pre-existing immune activation and tumors with a higher burden of mutations than patients who did not respond to BCG. They also identified potential biomarkers for the identification of patients most likely to benefit from either surgery alone or BCG therapy and, by elimination, those who are likely to need alternative therapies.
Field-effect-informed urine liquid biopsy for bladder cancer
Cell, 2026 January 27