Circulating Tumor DNA Assessment for Treatment Monitoring Adds Value to PSA in Metastatic Castration-Resistant Prostate Cancer - Article Summary

Q: What clinical question does the study address?

It tests whether baseline and early ctDNA tumor fraction (TF) can identify patients more likely to benefit from enzalutamide after abiraterone progression in metastatic castration-resistant prostate cancer.

Q: How was ctDNA measured and what timepoints were analyzed?

ctDNA TF was quantified from plasma using a tissue-agnostic assay without buffy coat sequencing. The analysis focused on baseline TF, changes to cycle 3 day 1 (C3D1), and detection at C3D1 alone.

Sep 21, 2026

Uploaded by Theodore

Evaluates how circulating tumor DNA (ctDNA) tumor fraction (TF) can guide treatment monitoring in metastatic castration-resistant prostate cancer after abiraterone progression. Using the phase III IMbassador250 trial, ctDNA TF at baseline, early changes by cycle 3 day 1, and detection at cycle 3 day 1 were compared with response measures including rPFS, median OS, and PSA reduction. ctDNA TF detection correlated with worse outcomes and, when discordant with PSA response, improved outcome stratification versus PSA alone. Concludes that ctDNA TF is a minimally invasive complementary biomarker to PSA for refining personalized enzalutamide-based care.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Purpose

Experimental Design

Results

Conclusions

Introduction

Circulating Tumor DNA Assessment for Treatment Monitoring Adds Value to PSA in Metastatic CastrationResistant Prostate Cancer Christopher J. Sweeney1, Russell Petry2, Chang Xu2, Merrida Childress2, Jie He2, David Fabrizio2, Ole Gjoerup2, Samantha Morley2, Timothy Catlett2, Zoe J. Assaf3, Kobe Yuen3, Matthew Wongchenko3, Kalpit Shah3, Pratyush Gupta3, Priti Hegde2, Lincoln W. Pasquina2, Sanjeev Mariathasan3, Ryon P. Graf2, and Thomas Powles4 | | | A | | B | S | | T | R | | A | | C | T | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Purpose: Enzalutamide after abiraterone progression is commonly used in metastatic castration-resistant prostate cancer despite a low rate of clinical benefit. Analyzing IMbassador250, a phase III trial assessing enzalutamide with or without atezolizumab after abiraterone, we hypothesized that baseline and early changes in circulating tumor DNA (ctDNA) tumor fraction (TF) may identify patients more likely to exhibit survival benefit from enzalutamide.
Experimental Design: ctDNA was quantified from plasma samples using a tissue-agnostic assay without buffy coat sequencing. Baseline ctDNA TF, changes in ctDNA TF from baseline to cycle 3 day 1 (C3D1), and detection at C3D1 alone were compared with overall response rate, radiographic progression-free survival (rPFS), median OS (mOS), and 50% reduction in PSA.
􀀶 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Results: ctDNA TF detection at baseline and/or C3D1 was associated with shorter rPFS and OS in 494 evaluable patients. Detection of ctDNA TF at C3D1, with or without detection at cycle 1 day 1, was associated with worse rPFS and mOS than lack of detection. When ctDNA TF and PSA response at C3D1 were discordant, patients with (ctDNA TF undetected/PSA not reduced) had more favorable outcomes than (ctDNA TF detected/ PSA reduced; mOS 22.1 vs. 16 months; P < 0.001) .
Conclusions: In a large cohort of patients with metastatic castration-resistant prostate cancer receiving enzalutamide after abiraterone, we demonstrate the utility of a new tissue-agnostic assay for monitoring molecular response based on ctDNA TF detection and dynamics. ctDNA TF provides a minimally invasive, complementary biomarker to PSA testing and may refine personalized treatment approaches. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Introduction Novel hormonal therapies such as abiraterone and enzalutamide have transformed the care of patients with advanced prostate cancer. However, patients eventually develop resistance and require novel therapeutic approaches. Like abiraterone, enzalutamide targets the androgen receptor (AR) signaling axis (1–4), and mechanisms of resistance to abiraterone often result in cross-resistance to enzalutamide. Still, following abiraterone progression, enzalutamide is the most-used regimen in the treatment of metastatic castration-resistant prostate cancer (mCRPC; ref. 5) despite the known low rate of net clinical benefit (6, 7)

FAQs

What clinical question does the study address?

It tests whether baseline and early ctDNA tumor fraction (TF) can identify patients more likely to benefit from enzalutamide after abiraterone progression in metastatic castration-resistant prostate cancer.

How was ctDNA measured and what timepoints were analyzed?

ctDNA TF was quantified from plasma using a tissue-agnostic assay without buffy coat sequencing. The analysis focused on baseline TF, changes to cycle 3 day 1 (C3D1), and detection at C3D1 alone.

How did ctDNA TF relate to imaging, survival, and PSA response?

ctDNA TF detection at baseline and/or C3D1 was associated with shorter radiographic progression-free survival (rPFS) and overall survival (OS). When ctDNA TF and PSA response at C3D1 were discordant, outcomes differed by whether ctDNA TF was detected.

Sep 21, 2026

Uploaded by Theodore