Introduction:

Neoadjuvant therapy followed by radical cystectomy with lymphadenectomy remains the gold standard of treatment in patients with muscle-invasive bladder cancer. Pathologically positive lymph node (pN+) disease is known to convey a poor prognosis. Tumor-informed circulating tumor DNA (ctDNA) has emerged as a possible novel prognostic biomarker in the field. We seek to assess recurrence-free survival (RFS) for patients undergoing robotic-assisted radical cystectomy (RARC) with extended pelvic lymphadenectomy (ePLND) and to assess whether ctDNA status can be a prognostic marker for RFS outcomes in patients with pN+ disease.

Methods:

Patients who underwent RARC + ePLND during 2015-2023 were included. A sub-group analysis (n=108) of patients who had prospectively collected serial-longitudinal tumor-informed ctDNA analyses during 2021-2023 was performed. Survival analysis and Cox-regression model were conducted.

Results:

Included were 458 patients with a median age of 69 (IQR 63-76), and a median follow-up time of 20 months (IQR 10-37). RFS for pN0 (n=353) and pN+ (n=105) at 12, 24 and 36 months were 87% vs. 55%, 80% vs. 40%, and 75% vs. 36%, respectively (log-rank, p<0.0001). Patients with pN+ disease had similar RFS to patients with pN0 disease if they had undetectable precystectomy ctDNA status (Figure 1A), undetectable postcystectomy ctDNA status (Figure 1B), or among patients that converted from precystectomy detectable to undetectable status at the postcystectomy period (Figure 1C). On Cox-regression multivariate sub-group analysis detectable precystectomy ctDNA status (HR=4.45 [1.55-12.7], p=0.005), and having both ≥pT3 with pN+ disease was predictive of disease recurrence (Table 1A). In the postcystectomy period detectable ctDNA status in the minimal residual disease window (HR=2.89 [1.12-7.4], p=0.028 was predictive of disease relapse (Table 1B).

Conclusion:

Patients with pN+ after RARC + ePLND fared worse than patients with pN0 disease. Undetectable ctDNA status was informative of RFS regardless of nodal status at both the precystectomy and the minimal residual disease window. Patients with undetectable ctDNA status and pN+ disease may benefit from treatment de-escalation.

Funding: N/A