Alessio Crippa, Bram De Laere, Andrea Discacciati, Berit Larsson, Maria Persson, Susanne Johansson, Sanne D'hondt, Marie Hjälm-Eriksson, Linn Pettersson, Gunilla Enblad, Anders Ullén, Nicolaas Lumen, Camilla Thellenberg Karlsson, Johan Sandzén, Elin Jänes, Christophe Ghysel, Martha Olsson, Brieuc Sautois, Peter Schatteman, Wendy De Roock, Siska Van Bruwaene, Ingrida Verbiene, Jochen Darras, Els Everaert, Daan De Maeseneer, Mats Anden, Michiel Strijbos, Daisy Luyten, Ashkan Mortezavi, Jan Oldenburg, Piet Ost, Johan Lindberg, Henrik Grönberg, Martin Eklund
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引用次数: 0
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.
期刊介绍：
Journal Name: European Urology Oncology
Affiliation: Official Journal of the European Association of Urology
Focus:
First official publication of the EAU fully devoted to the study of genitourinary malignancies
Aims to deliver high-quality research
Content:
Includes original articles, opinion piece editorials, and invited reviews
Covers clinical, basic, and translational research
Publication Frequency: Six times a year in electronic format
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