UNDETECTABLE PRECYSTECTOMY TUMOR-INFORMED CTDNA AND CONVERSION DYNAMICS AFTER RADICAL CYSTECTOMY PREDICTS IMPROVED ONCOLOGICAL OUTCOMES

Introduction

umor-informed circulating tumor DNA (ctDNA) has emerged as a novel prognostic biomarker in bladder cancer. We seek to assess recurrence-free survival (RFS) outcomes in patients with undetectable precystectomy ctDNA and to evaluate if patients who converted from detectable to undetectable ctDNA status post radical cystectomy have similar RFS outcomes as those with persistently undetectable ctDNA status.

Methods

Patients who underwent radical cystectomy had prospectively and longitudinally collected tumor-informed ctDNA analyses during 2021-2023. The ctDNA status was informed from the pre-cystectomy specimen. The minimal residual disease (MRD) window was defined as the initial 90 days after radical cystectomy. RFS was evaluated using the Kaplan-Meier method.

Results

The cohort included 135 patients with 647 ctDNA analyses. The median age was 71 years (IQR 63-77). During a median follow-up time of 11 months (IQR 7-18), 41 patients (30%) had a recurrence. Precystectomy undetectable ctDNA status was found in 54 patients (40%). The RFS rates at 6, 12, and 21 months were 98%, 93%, and 82%, respectively. Seventy-seven patients had undetectable ctDNA status at the MRD window available for conversion dynamics analysis (Table 1); 43 had persistently undetectable ctDNA status (both at precystectomy and MRD window) and 31 converted from precystectomy detectable to MRD undetectable status (conversion group). The persistently undetectable group had significantly better RFS than the conversion group (log-rank, p=0.0002), with 12- month RFS rates of 97% vs. 51%, and 18-month RFS rates of 88% vs. 51%, respectively (Figure 1).

Conclusions

Patients with undetectable precystectomy ctDNA status have a favorable prognosis and may be candidates for treatment de-escalation. Those with persistently undetectable ctDNA had superior RFS compared to the conversion group. Precystectomy ctDNA status should be incorporated in trials examining the use of ctDNA in clinical decision-making.