Urine Tumor DNA Stratifies Recurrence Risk During BCG in High-Risk NMIBC

Key Takeaways

• Before the first BCG treatment, 40% of patients were utDNA positive, and that group had lower 12-month recurrence-free survival than utDNA-negative patients.
• Among clinically negative patients after BCG, post-BCG utDNA positivity was associated with markedly worse 12-month recurrence-free survival than utDNA negativity.
• Urine testing first identified 33% of future recurrences during negative clinical surveillance, with a median 4.1-month lead time, and those cases later included cystectomy and muscle-invasive progression.

In a multicenter cohort of patients with high-risk non-muscle-invasive bladder cancer receiving intravesical BCG, clinically negative patients with post-BCG utDNA positivity had 12-month recurrence-free survival of 25%, versus 91% in utDNA-negative patients.

The study evaluated utDNA testing in patients receiving intravesical BCG, described by the researchers as the preferred treatment for high-risk NMIBC. Pretreatment and post-treatment urine samples were analyzed by UroAmp, and utDNA disease classification plus genomic disease burden were determined with previously established tumor-naive algorithms. Kaplan-Meier recurrence-free survival analyses and Cox proportional hazards were used to compare recurrence patterns during BCG, with baseline and post-treatment utDNA status assessed as markers of recurrence.

Before the first BCG treatment, 40% of patients, 23 of 57, were utDNA positive. Pretreatment utDNA-positive patients had 12-month recurrence-free survival of 61% versus 85% for utDNA-negative patients. The hazard ratio was 3.2, and P = .04.

After BCG, the analysis focused on patients who were clinically negative but still had measurable molecular signal in urine. In that subgroup, 19% of patients, 8 of 43, were utDNA positive after treatment. Their hazard ratio for recurrence-free survival was 10.0, with P < .001, relative to utDNA-negative patients.

An earlier molecular detection signal also appeared among patients who later developed recurrence. Among future recurrences, 33% were first detected by urine tumor DNA analysis while clinical surveillance remained negative. The median interval from molecular detection to clinical diagnosis was 4.1 months over standard of care. Among those lead-time cases, 67% later underwent radical cystectomy and 33% progressed to muscle-invasive disease.