Prognostic Potential of ctDNA in Lymph Node-Positive Bladder Cancer Post-RARC

A recent study has demonstrated the significant prognostic value of circulating tumor DNA (ctDNA) in patients with pathologically positive lymph nodes (pN+) following robotic-assisted radical cystectomy (RARC) with extended pelvic lymphadenectomy (ePLND). The findings, based on data from 458 patients treated between 2015 and 2023, highlight ctDNA as a robust biomarker for recurrence-free survival (RFS) and its potential role in refining treatment strategies for muscle-invasive bladder cancer (MIBC). The data will be presented at the Society of Urologic Oncology 2024 Annual Meeting by Reuben Ben-David, MD, of the Ichan School of Medicine, Mount Sinai Hospital.

Patients with pN+ disease exhibited markedly worse RFS compared to those with pN0 disease, with survival rates at 12, 24, and 36 months of 55%, 40%, and 36%, respectively, versus 87%, 80%, and 75%, respectively, for the pN0 cohort. Circulating tumor DNA status emerged as a critical factor in stratifying outcomes. Patients with undetectable ctDNA levels either before or after cystectomy, regardless of nodal involvement, demonstrated RFS rates comparable to those with pN0 disease. Additionally, individuals who transitioned from detectable ctDNA prior to surgery to undetectable levels in the postoperative period experienced improved survival outcomes.

In multivariate analysis, detectable ctDNA before cystectomy was strongly predictive of disease recurrence, with a hazard ratio (HR) of 4.45. Detectable ctDNA in the minimal residual disease window post-surgery also correlated with an elevated risk of relapse (HR, 2.89). These findings suggest that ctDNA is not only a marker of disease burden but also a potential guide for identifying high-risk patients.

This study emphasizes the potential of ctDNA as a transformative tool in the management of MIBC. For patients with pN+ disease, the detection of undetectable ctDNA levels could support treatment de-escalation, sparing these individuals from unnecessary therapeutic intensity while maintaining oncologic outcomes.