评估卵巢癌CA-125临床前可检测阶段、体内肿瘤倍增时间及早期检测窗口：英国卵巢癌筛查协作组的探索性分析
Estimating the ovarian cancer CA-125 preclinical detectable phase, in-vivo tumour doubling time, and window for detection in early stage: an exploratory analysis of UKCTOCS.
作者信息
Bedia Jacob S, Jacobs Ian J, Ryan Andy, Gentry-Maharaj Aleksandra, Burnell Matthew, Singh Naveena, Manchanda Ranjit, Kalsi Jatinderpal K, Dawnay Anne, Fallowfield Lesley, McGuire Alistair J, Campbell Stuart, Parmar Mahesh K B, Menon Usha, Skates Steven J
机构信息
MGH Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA.
Department of Women's Cancer, Elizabeth Garrett Anderson Institute for Women's Health, UCL, London, UK.
出版信息
EBioMedicine. 2025 Feb;112:105554. doi: 10.1016/j.ebiom.2024.105554. Epub 2025 Jan 13.
BACKGROUND
The ovarian cancer (OC) preclinical detectable phase (PCDP), defined as the interval during which cancer is detectable prior to clinical diagnosis, remains poorly characterised. We report exploratory analyses from the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).
METHODS
In UKCTOCS between Apr-2001 and Sep-2005, 101,314 postmenopausal women were randomised to no screening (NS) and 50,625 to annual multimodal screening (MMS) (until Dec-2011) using serum CA-125 interpreted by the Risk of Ovarian Cancer Algorithm (ROCA). All provided a baseline blood sample. Women with invasive epithelial OC diagnosed between randomisation and trial censorship (Dec-2014) in the MMS and NS arms with two or more CA-125 measurements, including one within two years of diagnosis were included. OC-free women (2:1 to cases) from the MMS arm provided information on baseline CA-125 distribution. CA-125 measurements were obtained from MMS results, secondary analysis of baseline samples, and medical records. PCDP duration and in-vivo tumour doubling time were estimated using the change-point model underlying ROCA. Early-stage (Stage I and II) PCDP was estimated from a Bayesian model for the probability of early stage given a CA-125 measurement.
FINDINGS
Of 541 women (2371 CA-125 measurements) with high-grade serous cancer (HGSC), 93% (504/541) secreted CA-125 into the circulation. Median CA-125 PCDP duration for clinically-diagnosed HGSC was 15.2 (IQR 13.1-16.9, 95% IPR 9.6-21.8) months, of which 11.9 (IQR 10.5-13.1, 95% IPR 7.5-16.5) months was in early stage. The median HGSC in-vivo tumour doubling time for cancers secreting CA-125 was 2.9 (IQR 2.3-3.7, 95% IPR 1.5-7.6) months.
INTERPRETATION
We report a comprehensive characterisation of the OC CA-125 PCDP. The 12-month window for early-stage detection and short tumour doubling time of HGSC provide a benchmark for researchers evaluating novel screening approaches including need to reduce diagnostic workup interval. Equally the findings provide urgent impetus for clinicians to reduce intervals from presentation to treatment onset.
FUNDING
NCI Early Detection Research Network, Concord (MA) Detect Ovarian Cancer Early Fund, MRC Clinical Trials Unit at UCL Core Funding.
背景
卵巢癌（OC）的临床前可检测阶段（PCDP），即临床诊断前癌症可被检测到的时间段，目前仍缺乏充分的特征描述。我们报告了来自英国卵巢癌筛查协作试验（UKCTOCS）的探索性分析结果。
方法
在2001年4月至2005年9月的UKCTOCS研究中，101,314名绝经后女性被随机分配至不进行筛查（NS）组，50,625名被随机分配至每年进行多模式筛查（MMS）组（直至2011年12月），采用卵巢癌风险算法（ROCA）解读血清CA - 125结果。所有参与者均提供了基线血样。纳入在MMS组和NS组中，随机分组至试验审查（2014年12月）期间被诊断为侵袭性上皮性OC且有两次或更多次CA - 125测量值的女性，其中包括诊断前两年内的一次测量值。来自MMS组的无OC女性（病例与对照比例为2:1）提供了关于基线CA - 125分布的信息。CA - 125测量值来自MMS结果、基线样本的二次分析以及医疗记录。使用ROCA基础的变点模型估计PCDP持续时间和体内肿瘤倍增时间。早期（I期和II期）PCDP通过贝叶斯模型根据CA - 125测量值计算早期阶段的概率来估计。
结果
在541名高级别浆液性癌（HGSC）女性（2371次CA - 125测量值）中，93%（504/541）的患者将CA - 125分泌到循环中。临床诊断为HGSC的患者，CA - 125的PCDP持续时间中位数为15.2（四分位间距13.1 - 16.9，95%可信区间9.6 - 21.8）个月，其中11.9（四分位间距10.5 - 13.1，95%可信区间7.5 - 16.5）个月处于早期阶段。分泌CA - 125的癌症患者，HGSC的体内肿瘤倍增时间中位数为2.9（四分位间距2.3 - 3.7，95%可信区间1.5 - 7.6）个月。
解读
我们报告了OC的CA - 125 PCDP的全面特征。HGSC的12个月早期检测窗口期和较短的肿瘤倍增时间为研究人员评估包括缩短诊断检查间隔需求在内的新型筛查方法提供了一个基准。同样，这些发现也为临床医生缩短从就诊到开始治疗的间隔时间提供了迫切的动力。
资助
美国国立癌症研究所早期检测研究网络（NCI Early Detection Research Network）、马萨诸塞州康科德市早期发现卵巢癌基金（Concord (MA) Detect Ovarian Cancer Early Fund）、伦敦大学学院医学研究理事会临床试验单位核心基金（MRC Clinical Trials Unit at UCL Core Funding）。
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