Post-IMvigor011 Era: CtDNA-Guided Postoperative Adjuvant Treatment Stratification in Muscle-Invasive Bladder Cancer.

Area of Science:

• Oncology
• Molecular Diagnostics
• Genitourinary Cancers

Background:

• Muscle-invasive bladder cancer (MIBC) shows significant postoperative variability.
• Current methods incompletely detect residual disease after radical cystectomy.
• Circulating tumor DNA (ctDNA) is a promising liquid biopsy for molecular residual disease (MRD).

Purpose of the Study:

• To review the evolution of ctDNA from prognostic marker to actionable biomarker in MIBC.
• To synthesize strategies for treatment escalation and de-escalation based on ctDNA status.
• To analyze barriers and future directions for ctDNA-guided MIBC management.

Main Methods:

• Review of prospective randomized trials, including IMvigor011.
• Analysis of ctDNA kinetics, assay selection, and potential interferences (e.g., CHIP).
• Discussion of emerging data from TOMBOLA, MODERN, and multi-analyte approaches.

Main Results:

• The IMvigor011 trial demonstrated ctDNA-guided adjuvant atezolizumab improves survival in ctDNA-positive patients.
• Persistently ctDNA-negative status supports surveillance but lacks randomized proof for omitting adjuvant therapy.
• ctDNA is established as an actionable marker for molecular relapse.

Conclusions:

• ctDNA monitoring is clinically relevant for guiding adjuvant therapy in MIBC.
• Integrating ctDNA into perioperative care requires addressing implementation challenges.
• Future research aims to establish ctDNA-guided management as a broader risk-adapted strategy.