A new study concluded that some people with muscle-invasive bladder cancer can safely avoid bladder removal if blood and urine tumor DNA tests show no signs of lingering cancer, according to a study published recently in the Proceedings of the National Academy of Sciences.
Researchers found that measuring circulating tumor DNA in plasma and tumor DNA in urine can help identify which patients are most likely to remain cancer-free after chemotherapy and immunotherapy without undergoing radical cystectomy, the life-altering surgery that removes the bladder.
The findings come from the HCRN GU16-257 clinical trial (NCT03558087), which enrolled 76 patients with cT2-4aN0M0 urothelial bladder cancer. After tumor removal through cystoscopy, patients received four cycles of gemcitabine, cisplatin and nivolumab. Those with a clinical complete response, meaning no visible cancer on repeat cystoscopy, biopsies, urine cytology or imaging, could choose to keep their bladder and receive eight additional cycles of nivolumab followed by surveillance.
Of the 76 patients, 33 (or 43%) achieved a complete response. With a median follow-up of 47.3 months, the three-year metastasis-free survival rate was 90% for those with a complete response compared with 64% for those without. The three-year overall survival rate was 97% versus 72%. Among patients with a complete response, 69% maintained bladder-intact survival at three years.
Read more about the prognosis of bladder cancer
Tumor DNA testing provided important clues about risk. At baseline, circulating tumor DNA was detectable in 64% of patients but dropped to 20% after four treatment cycles. Only one of the 22 patients with undetectable baseline circulating tumor DNA developed metastatic disease. Patients with detectable circulating tumor DNA before treatment had a significantly higher risk of metastasis. Undetectable circulating tumor DNA before or after therapy was associated with extremely low metastatic risk.
Urine tumor DNA proved even more sensitive for detecting residual disease in the bladder. At restaging, 70% of patients had detectable urine tumor DNA. Among those with a complete response, detectable urine tumor DNA was linked to worse bladder-intact survival, with a hazard ratio of 6.47. High-grade bladder recurrences occurred in 70% of patients with detectable urine tumor DNA compared with 29% of those without. The median time to recurrence after a positive urine test was 12.9 months.
“Despite the need for further investigation, our results establish a framework for incorporating MRD [molecular residual disease] detection into response-guided bladder-sparing approaches in MIBC [muscle-invasive bladder cancer],” stated the study’s authors.
For patients, these results suggest that personalized DNA testing could reduce unnecessary bladder removal and its permanent effects on urinary function, sexual health and daily life. At the same time, positive DNA tests may signal the need for closer monitoring or earlier surgery. Larger randomized trials are still needed, but this approach may move care closer to truly individualized treatment.
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