Prognostic Value of the Circulating Tumor DNA Fraction in Metastatic Castration-resistant Prostate Cancer: Results from the ProBio Platform Trial.
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Crippa A, Laere B, Discacciati A, Larsson B, Persson M, Johansson S, D'hondt S, Hjälm-Eriksson M, Pettersson L, Enblad G, Ullén A, Lumen N, Karlsson CT, Sandzén J, Jänes E, Ghysel C, Olsson M, Sautois B, Schatteman P, Roock W, Bruwaene SV, Verbiene I, Darras J, Everaert E, Maeseneer D, Anden M, Strijbos M, Luyten D, Mortezavi A, Oldenburg J, Ost P, Lindberg J, Grönberg H, Eklund M, ProBio Investigators
Eur Urol Oncol - (-) - [2025-04-21; online 2025-04-21]
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). 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. 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. 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.
Bioinformatics (NBIS) [Service]
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Clinical Genomics Stockholm [Service]
PubMed 40263079
DOI 10.1016/j.euo.2025.02.002
Crossref 10.1016/j.euo.2025.02.002
pii: S2588-9311(25)00037-9
ClinicalTrials.gov: NCT03903835