Using ctDNA to Inform Adjuvant Therapy for Urologic Malignancies

Area of Science:

• Oncology
• Genitourinary Cancers
• Molecular Diagnostics

Background:

• Adjuvant therapy decisions for genitourinary (GU) cancers rely on clinicopathologic factors that incompletely predict individual recurrence risk.
• Current approaches lead to imprecise patient selection, resulting in both overtreatment and undertreatment of GU malignancies.
• Minimal residual disease (MRD) detection is crucial for optimizing adjuvant treatment strategies.

Purpose of the Study:

• To review the evidence for using circulating tumor DNA (ctDNA) to guide adjuvant therapy decisions in bladder, kidney, and prostate cancers.
• To highlight disease-specific applications of ctDNA in the post-neoadjuvant, post-cystectomy, and post-prostatectomy settings.
• To explore the potential of ctDNA as a biomarker for MRD in GU malignancies.

Main Methods:

• Literature review summarizing current evidence on ctDNA in GU cancer adjuvant therapy.
• Analysis of ctDNA's role in detecting MRD and predicting oncologic outcomes.
• Exploration of ctDNA applications across different GU cancer types and treatment settings.

Main Results:

• ctDNA detection indicates persistent tumor and can precede radiographic recurrence.
• ctDNA negativity is consistently linked to favorable oncologic outcomes.
• Evidence supports ctDNA's utility in refining adjuvant treatment decisions for bladder, kidney, and prostate cancers.

Conclusions:

• ctDNA offers a minimally invasive approach to assess MRD in GU malignancies.
• ctDNA may facilitate a paradigm shift towards biologically informed escalation and de-escalation of adjuvant therapy.
• Prospective validation in biomarker-driven clinical trials is essential to confirm ctDNA's role in clinical practice.