Blood Test May Help Detect Bladder Cancer Recurrence Earlier
Bladder preserving trimodality therapy offers patients with muscle-invasive bladder cancer a chance to avoid radical surgery, but it comes with a challenge: detecting cancer spread early enough to intervene. A new study from Moffitt Cancer Center suggests that circulating tumor DNA testing could provide an important tool to fill that gap. Findings from the study were presented at the 2025 American Society for Radiation Oncology annual meeting.
Muscle-invasive bladder cancer is an aggressive disease with a high risk of spreading to distant sites. Circulating tumor DNA, or ctDNA, refers to small fragments of DNA that are released into the bloodstream when cancer cells die and break apart. Because these fragments carry the same genetic mutations as the tumor, they serve as a kind of molecular fingerprint of the cancer.
Dekuang Zhao, DO, PhD
“It is estimated that nearly a quarter of patients with muscle-invasive bladder cancer will eventually develop distant metastases after definitive treatment with either radical cystectomy or bladder preserving trimodality therapy,” said Dekuang Zhao, DO, PhD, a radiation oncology resident at Moffitt and lead author of the study. “Currently, monitoring relies on cystoscopy, urine cytology and CT scans. While imaging detects larger tumors, it has limitations in finding early micro metastatic disease. Given that metastatic disease is the main contributor of bladder cancer-related death, early recognition before imaging detection remains a major clinical challenge.”
Circulating Tumor DNA as an Early Signal
G. Daniel Grass, MD, PhD
To address this, researchers studied ctDNA by analyzing blood samples from patients who had completed trimodality therapy. The team found that ctDNA positivity often signaled cancer progression weeks before conventional imaging. On average, ctDNA identified metastasis 57 days earlier than standard scans.
“Early detection of metastatic spread by ctDNA may provide a window of opportunity for surveillance intensification or a change in imaging approach, such as performing a PET/CT instead of a standard CT scan,” said G. Daniel Grass, MD, PhD, section head of genitourinary radiation oncology at Moffitt and senior author of the study. “This may give us the chance to initiate salvage therapy before the disease becomes more advanced.”
Potential to Ease Patient Burden
The study also highlights the potential of ctDNA to streamline posttreatment monitoring. Patients who choose bladder preserving therapy currently undergo frequent invasive cystoscopies and whole-body imaging. Zhao says ctDNA could someday serve as a less burdensome marker of recurrence.
Following his oral presentation at #ASTRO25, Dekuang Zhao, DO (@DK_18621), summarizes results on ctDNA in bladder-preserving TMT.
— Moffitt Cancer Center (@MoffittNews) September 28, 2025
👉 ctDNA positivity predicted metastatic progression with high accuracy, preceded clinical detection by a median of 57 days and up to 139 days, and… pic.twitter.com/llYoasuymv
“Like PSA testing in prostate cancer, a drop in ctDNA after trimodality therapy may indicate a successful response and reassure the patient and their physicians,” Zhao said. “Though our data is preliminary, sustained negative ctDNA values during surveillance may eventually allow for fewer imaging scans or cystoscopies. Since ctDNA comes from a simple blood draw, it can be performed easily with little risk.”
Expanding Options Beyond Surgery
The study focused on trimodality therapy because while radical cystectomy has long been the standard of care for muscle-invasive bladder cancer, bladder preservation is now a viable alternative for carefully selected patients.
“A growing amount of data suggests ctDNA can help stratify risk after cystectomy,” Zhao said. “We wanted to know if the same held true for trimodality therapy, and our results suggest it does.”
This research adds to growing evidence that ctDNA could play a central role in tailoring cancer surveillance. Larger prospective trials are still needed to validate the approach, but Zhao believes the potential is clear.
“CtDNA monitoring may one day allow for more personalized surveillance programs based on a patient’s risk,” he said.
