Key Clinical Summary: Coordinating ctDNA Testing Across the Care Continuum

This is a micro-learning module summary of a presentation by Dr. John P. Sfakianos which you can find here. Before participating, please read our CME and disclosure information which can be found here.

This program is supported by an independent educational grant from Genentech. This accredited education activity is available to U.S. healthcare professionals only.

Introduction
This summary explores practical, evidence‑based strategies for integrating tumor‑informed circulating tumor DNA (ctDNA) testing into perioperative management of muscle‑invasive bladder cancer (MIBC), outlining how coordinated workflows between urologists, medical oncologists, and advanced practice providers enable timely minimal residual disease (MRD) assessment. It reviews the rationale for early tissue acquisition, the prognostic value of single‑time‑point and serial ctDNA testing, and the operational models that support longitudinal monitoring across the care continuum.

Coordinating Early Tissue Acquisition and Assay Initiation

Urologists are uniquely positioned to initiate ctDNA testing because TURBT (transurethral resection of bladder tumor) provides ample tissue for whole‑exome sequencing required for tumor‑informed assays.
A single TURBT specimen is typically sufficient to generate a lifelong personalized assay, enabling repeated plasma testing without the need for additional tumor sampling.
Early ordering, ideally at the postoperative pathology review, ensures ctDNA results are available when multidisciplinary teams make definitive treatment decisions.
Standardized institutional workflows help avoid delays in tissue retrieval, assay initiation, and communication of results to oncology colleagues.

Precision Medicine Applications Across the Perioperative Pathway

ctDNA supports individualized treatment selection by identifying patients at high risk for early recurrence who may benefit from intensified systemic therapy.
In both muscle‑invasive and select non–muscle‑invasive settings, ctDNA positivity can prompt closer surveillance or earlier therapeutic intervention.
Serial ctDNA monitoring provides dynamic insight into treatment response during neoadjuvant therapy and systemic therapy, complementing but not replacing imaging.
ctDNA may eventually help differentiate candidates for chemotherapy versus immunotherapy, though predictive use remains investigational.

Prognostic Value of ctDNA Before and After Neoadjuvant Chemotherapy

Prospective data demonstrate that ctDNA positivity after TURBT and before neoadjuvant chemotherapy is strongly prognostic for recurrence risk.
Lack of ctDNA clearance during neoadjuvant therapy is a more powerful predictor of recurrence than pathologic response at cystectomy.
Median lead time from ctDNA positivity to radiographic recurrence is approximately 96 days, enabling earlier identification of molecular relapse.
Patients who remain ctDNA‑negative throughout neoadjuvant therapy and after cystectomy have excellent outcomes, with 100% overall survival reported in some cohorts.

Integrating ctDNA Into Multidisciplinary Decision‑Making

Multidisciplinary review is essential when ctDNA is positive before neoadjuvant therapy, as these patients may require intensified systemic therapy or modified perioperative planning.
Persistent ctDNA positivity despite stable imaging should prompt coordinated evaluation of high‑risk features rather than passive observation.
Cross‑specialty communication ensures that ctDNA results are interpreted in context with pathology, imaging, and clinical risk factors.
Shared access to ctDNA results across teams supports consistent messaging to patients and timely escalation of care when needed.

Content is accurate as of the date of release on 16 March 2026.