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. 2025 Apr 21:S2588-9311(25)00037-9.
doi: 10.1016/j.euo.2025.02.002. Online ahead of print.

Prognostic Value of the Circulating Tumor DNA Fraction in Metastatic Castration-resistant Prostate Cancer: Results from the ProBio Platform Trial

Alessio Crippa  1 , Bram De Laere  2 , Andrea Discacciati  1 , Berit Larsson  1 , Maria Persson  1 , Susanne Johansson  1 , Sanne D'hondt  3 , Marie Hjälm-Eriksson  4 , Linn Pettersson  5 , Gunilla Enblad  6 , Anders Ullén  7 , Nicolaas Lumen  8 , Camilla Thellenberg Karlsson  9 , Johan Sandzén  10 , Elin Jänes  11 , Christophe Ghysel  12 , Martha Olsson  13 , Brieuc Sautois  14 , Peter Schatteman  15 , Wendy De Roock  16 , Siska Van Bruwaene  17 , Ingrida Verbiene  18 , Jochen Darras  19 , Els Everaert  20 , Daan De Maeseneer  21 , Mats Anden  22 , Michiel Strijbos  23 , Daisy Luyten  24 , Ashkan Mortezavi  25 , Jan Oldenburg  26 , Piet Ost  27 , Johan Lindberg  28 , Henrik Grönberg  29 , Martin Eklund  1 ; ProBio Investigators
Affiliations
Free article

Prognostic Value of the Circulating Tumor DNA Fraction in Metastatic Castration-resistant Prostate Cancer: Results from the ProBio Platform Trial

Alessio Crippa et al. Eur Urol Oncol. .
Free article

Abstract

Background and objective: The aim of this study was to evaluate the prognostic value of undetectable circulating tumor DNA (ctDNA) and the dose-response relationship between ctDNA levels and survival outcomes in metastatic castration-resistant prostate cancer (mCRPC).

Methods: We analyzed data for patients enrolled in the ProBio trial up to November 2022 who received an androgen receptor pathway inhibitor or taxane. We compared survival outcomes between patients with undetectable ctDNA and those with detectable ctDNA randomized to physician's choice or investigational arms. Time to no longer clinically benefiting (NLCB) and overall survival (OS) were assessed using Bayesian survival models, with results reported as survival time ratios (STRs). Dose-response relationships were estimated using spike-at-zero models.

Key findings and limitations: A total of 220 patients were included, of whom 139 had detectable ctDNA (56 in the physician's choice arm, 83 in investigational arms) and 81 had undetectable ctDNA. In comparison to the undetectable ctDNA group, the physician's choice arm had 60% shorter time to NLCB (STR 0.40, 90% credible interval [CrI] 0.31-0.51) and 51% shorter OS (STR 0.49, 90% CrI 0.38-0.61). Similar results were observed in comparison to the investigational arms. Dose-response analysis revealed that the undetectable ctDNA group had twofold longer time to NLCB (STR 2.05, 90% CrI 1.66-2.57) and 1.6-fold longer OS (STR 1.63, 90% CrI 1.33-2.05) in comparison to the subgroup with a ctDNA fraction of 2.5%. Every 10-point increment in the ctDNA fraction corresponded to a 10% reduction in NLCB and OS times.

Conclusions and clinical implications: Undetectable ctDNA at baseline predicts superior prognosis in mCRPC, suggesting potential for treatment de-escalation and less intensive monitoring for this subgroup of patients. This trial is registered on ClinicalTrials.gov as NCT03903835.

Keywords: Circulating tumor DNA; Dose-response; Platform trial; Prognostic biomarker; Prostate cancer.

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