(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL between May 30th and June 3rd, 2025, was host to a kidney and bladder cancers poster session. Ilana Epstein presented the results of a correlative analysis of circulating tumor DNA (ctDNA) dynamics with clinical response in muscle-invasive bladder cancer (MIBC) patients undergoing trimodality therapy (TMT).
Plasma circulating tumor DNA (ctDNA) dynamics have been shown to be associated with treatment response and clinical outcomes following radical cystectomy for MIBC. TMT is another standard of care treatment option for select MIBC patients. The association of plasma ctDNA with treatment response and clinical outcomes in MIBC patients treated with TMT remains poorly understood. The study investigators hypothesized that ctDNA dynamics are correlated with clinical outcomes in MIBC patients treated with TMT.
This study included select patients with non-metastatic MIBC who received TMT with definitive treatment intent at the Dana-Farber/Brigham and Women's Cancer Center or Massachusetts General Hospital. All patients had demographic and clinical data collected. The commercially available Signatera assay was used to measure plasma ctDNA prior to TMT and at regularly scheduled visits during surveillance following completion of TMT.
Signatera is a tumor-informed plasma ctDNA assay. Tissue from the initial transurethral resection of bladder tumor (TURBT) specimen undergoes whole exome sequencing (WES) and a personalized list of tumor-specific mutations is developed. DNA is then isolated from plasma collected via peripheral IV blood draws and the presence or absence of ctDNA is assessed. For samples in which ctDNA is detected, a mean tumor molecules per milliliter (MTM/ml) value is reported.
The cohort characteristics are summarized below (n=80). The median patient age was 75 years. 89% of patients were male. 23$ of patients had cT3-4 disease. 94% of patients had cN0 disease. The vast majority received concurrent chemotherapy (91%), with 20% and 11% receiving neoadjuvant chemotherapy and systemic therapy, respectively. The median follow-up was 11 months.
The study findings were as follows:
- ctDNA(+) prior to TMT: 18/56 (32%)
- ctDNA(+) prior to TMT ctDNA(-) after TMT: 10/14 (71%)
- ctDNA (-) prior to TMT ctDNA(+) at 1st post-TMT visit: 0 (0%)
- All 8 patients with a ctDNA(+) status at the first post-TMT assessment developed metastatic disease
- ctDNA(-) at 1st post- TMT assessment who have remained ctDNA(-) during follow-up: 53/56 (94%)
Patients with a ctDNA(-) status at the 1st post-TMT visit had superior modified bladder-intact free survival, compared to patients who were ctDNA(+) at the 1st post-TMT visit (p<0.001).
The study investigators concluded as follows:
- Accrual and follow-up are ongoing to further define the relationship between plasma ctDNA detectability and clinical outcomes in MIBC patients treated with TMT
- Integrating ctDNA into the clinical management of MIBC patients treated with TMT will require prospective validation.
- The role of urine tumor DNA (utDNA) for monitoring disease status and treatment response in MIBC patients treated with TMT is uncertain but warrants further investigation.
Presented by: Ilana Bensussen Epstein, BA, Senior Research Data Specialist, Dana-Farber Cancer Institute, Boston, MA
Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.