Abstract
Longitudinal CA125 algorithms are the current basis of ovarian cancer screening. We report on longitudinal algorithms incorporating multiple markers. In the multimodal arm of United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), 50,640 postmenopausal women underwent annual screening using a serum CA125 longitudinal algorithm. Women (cases) with invasive tubo-ovarian cancer (WHO 2014) following outcome review with stored annual serum samples donated in the 5 years preceding diagnosis were matched 1:1 to controls (no invasive tubo-ovarian cancer) in terms of the number of annual samples and age at randomisation. Blinded samples were assayed for serum human epididymis protein 4 (HE4), CA72-4 and anti-TP53 autoantibodies. Multimarker method of mean trends (MMT) longitudinal algorithms were developed using the assay results and trial CA125 values on the training set and evaluated in the blinded validation set. The study set comprised of 1363 (2–5 per woman) serial samples from 179 cases and 181 controls. In the validation set, area under the curve (AUC) and sensitivity of longitudinal CA125-MMT algorithm were 0.911 (0.871–0.952) and 90.5% (82.5–98.6%). None of the longitudinal multi-marker algorithms (CA125-HE4, CA125-HE4-CA72-4, CA125-HE4-CA72-4-anti-TP53) performed better or improved on lead-time. Our population study suggests that longitudinal HE4, CA72-4, anti-TP53 autoantibodies adds little value to longitudinal serum CA125 as a first-line test in ovarian cancer screening of postmenopausal women.
Highlights
Ovarian cancer is the most fatal of all gynaecological malignancies [1]
We report on the performance of longitudinal multi-marker algorithms incorporating CA125, human epididymis protein 4 (HE4), CA72-4 and anti-TP53 autoantibodies as a first-line test in ovarian cancer screening using the prospective specimen collection and the retrospective blinded evaluation (PRoBe) design [23] within the general population UKCTOCS trial
The multimodal screening (MMS) strategy consists of first-line screening using the longitudinal CA125 algorithm (ROCA) followed by repeat CA125
Summary
Ovarian cancer is the most fatal of all gynaecological malignancies [1]. Despite significant advances in treatment, the impact on mortality over the past three decades has been modest [2,3,4,5].A key contributing factor is diagnosis at advanced stages when survival is poor (5-year survival rates for stage III/IV disease 35% versus 90% for stage I) [6]. Ovarian cancer is the most fatal of all gynaecological malignancies [1]. Despite significant advances in treatment, the impact on mortality over the past three decades has been modest [2,3,4,5]. A key contributing factor is diagnosis at advanced stages when survival is poor (5-year survival rates for stage III/IV disease 35% versus 90% for stage I) [6]. Efforts over the past four decades have focused on early detection. Advances in understanding the natural history has clarified the need to focus on detecting invasive tubo-ovarian cancer (WHO 2014), especially Type II (high-grade serous) cancers as they account for most of the mortality. Since its discovery in 1981, CA125 remains the best performing marker for ovarian cancer
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