Photo Credit: Mohammed Haneefa Nizamudeen

The following is a summary of “Prognostic significance of circulating tumor DNA in patients with positive lymph node disease after robotic-assisted radical cystectomy: A contemporary analysis,” published in the September 2024 issue of Urology by Ben-David et al.

Neoadjuvant therapy followed by radical cystectomy with extended lymphadenectomy remains the gold standard for treating patients with muscle-invasive bladder cancer. However, pathologically positive lymph node (pN+) disease continues to indicate a poor prognosis. Tumor-informed circulating tumor DNA (ctDNA) has recently emerged as a potential novel biomarker for predicting recurrence-free survival (RFS). This study aims to evaluate RFS in patients undergoing robotic-assisted radical cystectomy (RARC) with extended pelvic lymphadenectomy (ePLND) and to explore the utility of ctDNA as a prognostic marker for RFS, particularly in those with pN+ disease.

A total of 458 patients who underwent RARC with ePLND between 2015 and 2023 were included in the study. Additionally, a subgroup analysis was conducted on 109 patients who had prospectively collected longitudinal tumor-informed ctDNA analyses between 2021 and 2023. Survival analysis and Cox regression models were used to evaluate RFS outcomes and the predictive value of ctDNA status. The median age of patients was 69 years (IQR 63–76), with a median follow-up period of 20 months (IQR 10–37). RFS at 12, 24, and 36 months for pN0 (n=353) versus pN+ (n=105) patients were 87% vs. 54%, 80% vs. 39%, and 74% vs. 35%, respectively (log-rank, P < 0.0001). Multivariate cox analysis identified ≥pT3 disease (HR=3.36, P < 0.001), pN+ status (HR=2.39, P < 0.001), and neoadjuvant therapy (HR=1.61, P=0.013) as significant predictors of disease relapse. Notably, patients with pN+  suffering from undetectable ctDNA status before or after surgery exhibited RFS rates comparable to pN0 patients with undetectable ctDNA. Furthermore, on subgroup analysis, detectable precystectomy ctDNA (HR=3.89, P=0.014), detectable ctDNA in the minimal residual disease (MRD) window (HR=2.89, P=0.028), and the presence of ≥pT3 disease with pN+ status (HR=4.2, P=0.009) were all strongly predictive of relapse.

In conclusion, patients with pN+ who underwent RARC had worse oncological outcomes than their pN0 counterparts. However, undetectable ctDNA status before or after surgery was a robust predictor of improved RFS, irrespective of nodal status. This finding suggests that patients with pN+ suffering from undetectable ctDNA may be suitable candidates for treatment de-escalation, underscoring the potential of ctDNA as a valuable prognostic biomarker in managing bladder cancer.

Source: sciencedirect.com/science/article/abs/pii/S1078143924005763