ctDNA Shows Promise as a Preoperative Biomarker of Disease Upstaging in Bladder Cancer

As circulating tumor DNA (ctDNA) is gradually becoming a novel biomarker for several malignancies, including bladder cancer, Reuben Ben-David, MD, and colleagues sought to determine if ctDNA detection prior to radical cystectomy is linked to poor outcomes and lymph node involvement.

Results of the study were presented at the 2024 American Urological Association Annual Meeting.

The retrospective study analyzed data from 87 patients who underwent robot-assisted radical cystectomy. Electronic medical records were used to collect baseline characteristics, as well as pathological, oncological, and imaging results.

The median follow-up period was 8 months. Preoperative positive ctDNA status was found in 45 patients, and 11 patients had non-muscle invasive bladder cancer (NMIBC). Disease progression was more common in the preoperative positive ctDNA group (41.5% vs 12.2%; P=.005) and was associated with higher risk of nodal (odds ratio [OR], 5.41; 95% CI, 1.52-24.1; P=.015) and locally advanced (OR, 3.1; 95% CI, 1.15-8.65; P=.026) disease upon univariate and multivariate analysis.

Preoperative positive ctDNA was also associated with higher rates of variant histology (48.9% vs 21.4%; P=.013) and disease upstaging on final pathology (51.1% vs 28.6%; P=.003), respectively. In a subgroup analysis of 11 patients with positive preoperative ctDNA status and NMIBC, 6 patients had disease upstaging, 2 had positive nodal disease, and 4 had locally advanced disease.

In 18 patients with NMIBC and preoperative negative ctDNA, only 1 patient had locally advanced T3a disease and none had nodal involvement.

Preoperative ctDNA can be successfully used as a biomarker to detect the possibility of disease upstaging, locally advanced disease, and nodal disease in patients with bladder cancer, irrespective of preoperative disease stage.

Physicians can use these biomarker data to determine disease status before cystectomy to select optimal patients for neoadjuvant treatment escalation.