循环肿瘤DNA分数在转移性去势抵抗性前列腺癌中的预后价值：来自ProBio平台试验的结果
Prognostic Value of the Circulating Tumor DNA Fraction in Metastatic Castration-resistant Prostate Cancer: Results from the ProBio Platform Trial.
作者信息
Crippa Alessio, Laere Bram De, Discacciati Andrea, Larsson Berit, Persson Maria, Johansson Susanne, D'hondt Sanne, Hjälm-Eriksson Marie, Pettersson Linn, Enblad Gunilla, Ullén Anders, Lumen Nicolaas, Karlsson Camilla Thellenberg, Sandzén Johan, Jänes Elin, Ghysel Christophe, Olsson Martha, Sautois Brieuc, Schatteman Peter, Roock Wendy De, Bruwaene Siska Van, Verbiene Ingrida, Darras Jochen, Everaert Els, Maeseneer Daan De, Anden Mats, Strijbos Michiel, Luyten Daisy, Mortezavi Ashkan, Oldenburg Jan, Ost Piet, Lindberg Johan, Grönberg Henrik, Eklund Martin
机构信息
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Human Structure and Repair Ghent University, Ghent, Belgium.
出版信息
Eur Urol Oncol. 2025 Apr 21. doi: 10.1016/j.euo.2025.02.002.
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.
背景与目的
本研究旨在评估转移性去势抵抗性前列腺癌（mCRPC）中循环肿瘤DNA（ctDNA）检测不到的预后价值以及ctDNA水平与生存结果之间的剂量反应关系。
方法
我们分析了截至2022年11月参加ProBio试验的患者数据，这些患者接受了雄激素受体通路抑制剂或紫杉烷治疗。我们比较了ctDNA检测不到的患者与随机分配至医生选择或研究组的ctDNA可检测到的患者的生存结果。使用贝叶斯生存模型评估不再临床获益（NLCB）时间和总生存期（OS），结果报告为生存时间比（STR）。使用零值处尖峰模型估计剂量反应关系。
主要发现与局限性
共纳入220例患者，其中139例ctDNA可检测到（医生选择组56例，研究组83例）,81例ctDNA检测不到。与ctDNA检测不到的组相比，医生选择组的NLCB时间缩短60%（STR 0.40，90%可信区间[CrI] 0.31 - 0.51），OS缩短51%（STR 0.49，90% CrI 0.38 - 0.61）。与研究组相比观察到类似结果。剂量反应分析显示，与ctDNA比例为2.5%的亚组相比，ctDNA检测不到的组NLCB时间延长两倍（STR 2.05，90% CrI 1.66 - 2.57），OS延长1.6倍（STR 1.63，90% CrI 1.33 - 2.05）。ctDNA比例每增加10个百分点，NLCB和OS时间相应缩短10%。
结论与临床意义
基线时ctDNA检测不到预示mCRPC患者预后较好，提示该亚组患者有可能降低治疗强度并减少密切监测。本试验已在ClinicalTrials.gov上注册，注册号为NCT03903835。
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