Prospective Evaluation of Circulating Tumor DNA in Metastatic Hormone-Sensitive Prostate Cancer.

Authors

Charles B Nguyen, Irene Tsung, Jessica K Lee, Lincoln W Pasquina, Amy Kasputis, Jennie L Lovett, Ryon P Graf, Amber Redmond, Frank C Cackowski, Elisabeth I Heath, David C Smith, Joshi J Alumkal, Todd M Morgan, Zachery R Reichert

Published in

JCO precision oncology. Volume 10. Issue 9. Pages e2501218. Epub Sep 09, 2026.

Abstract

There are few established prognostic biomarkers in metastatic hormone-sensitive prostate cancer (mHSPC). Disease volume and timing of metastases are prognostic and predictive factors but may be inadequate due to heterogeneity. Circulating tumor DNA (ctDNA) provides both circulating volume (tumor fraction [TF]) and genomic data. There are limited data on ctDNA in mHSPC.
This was a multicenter, prospective study of ctDNA testing in mHSPC. Presented here are the results before androgen-deprivation therapy initiation. The primary objective was to evaluate the association between TF and overall survival (OS) and time to mCRPC (TTCRPC). Secondary analyses included evaluating outcomes in subgroups of interest and key genomic subtypes.
Between 2018 and 2024, 85 patients were enrolled, of whom 72 (25% Black) had evaluable baseline ctDNA samples and are included herein. Baseline TF was positive in 46 patients (64%). Compared with patients with negative ctDNA TF, most patients with positive ctDNA TF had de novo (87% v 39%, P < .001) and high-volume disease (80% v 46%, P = .01). At a median follow-up of 20.8 months, median OS was not reached (NR) with those with negative ctDNA TF and 33 months with positive ctDNA TF (hazard ratio [HR], 3.33 [95% CI, 1.1 to 9.9]; P = .03). However, a negative TF at baseline was associated with an undetectable 7-month prostate-specific antigen, a validated OS surrogate. Median TTCRPC was NR versus 13 months (HR, 3.43 [95% CI, 1.5 to 7.9]; P = .004). ctDNA TF was also potentially prognostic in high-volume disease and those who received doublet therapy.
In this diverse cohort, a positive ctDNA TF at baseline was associated with worse outcomes in mHSPC and may potentially complement current further risk stratification tools.

PMID:
42715508
Bibliographic data and abstract were imported from PubMed on 10 Sep 2026.

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