Urine cell-free DNA multi-omics to detect molecular residual disease and predict survival in bladder cancer patients

Bladder cancer is the sixth most commonly diagnosed cancer in the US and the most expensive malignancy by lifetime cost per patient due to the significant cost associated with its diagnosis, treatment and surveillance. Treatment of muscle invasive bladder cancer typically involves chemotherapy followed by radical cystectomy, a morbid surgery that lowers the quality of life and could potentially be foregone altogether based on the observation of a pathologic complete response observed in some patients. Unfortunately, we have no way to know a priori who will achieve a pathological complete response to neoadjuvant treatment. Given this deficiency in the field, we developed a liquid biopsy modality to sensitively detect minimal residual disease following physicians choice chemotherapy, which we applied just prior to radical cystectomy, and correlated our results with pathological complete response. Bladder cancer patients whose urine harbored evidence of minimal residual disease based on multi modal urine tumor DNA analysis using urine Cancer Personalized Profiling by deep Sequencing and ultra low pass whole genome sequencing had significantly lower rates of pathologic complete response and significantly worse progression free and overall survival.