Risk-stratified CA125 screening integrating CA125 trajectories, trajectory-specific progression and transvaginal ultrasound for ovarian cancer

Sep 21, 2026

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Cancer antigen 125 (CA125) is widely used for ovarian cancer screening, but its effectiveness remains debated due to uncertainty around cutoff values and limited use of longitudinal CA125 trajectories. This study integrates CA125 trajectory patterns with trajectory-specific progression indicators and transvaginal ultrasound in the PLCO Trial. Time-dependent ROC and tdAUC analyses define optimized cutoffs, assess associations with incidence and mortality using hazard ratios, and evaluate whether risk-stratified screening reduces missed cases and improves overall accuracy.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Keywords

Introduction

Burden of ovarian cancer and rationale for screening

Limitations of current screening approaches

Duan etal. Journal of Ovarian Research (2024) 17:210 Journal of Ovarian Research [https://doi.org/10.1186/s13048-024-01535-9](https://doi.org/10.1186/s13048-024-01535-9) RESEARCH Open Access Risk-stratified CA125 screening integrating CA125 trajectories, trajectory-specific progression and transvaginal ultrasound for ovarian cancer Hongyuan Duan 1, Xiaomin Liu 1, Yu Zhang 1, Ya Liu 1, Yuting Ji 1, Yunmeng Zhang 1, Zeyu Fan 1, Siwen Liu 1, Lei Yang2, Tingting Xu3, Jing Tian4, Weiqin Li5, Zhangyan Lyu 1, Fangfang Song 1, Fengju Song 1 andYubei Huang 1* Abstract Backgrounds Cancer antigen 125 (CA125) is widely used for screening ovarian cancer (OC), yet its effectiveness remains debated. Potential factors may include ineffective cut-off value for CA125 in screening, as well as a lack of consideration for CA125 trajectories and trajectory-specific progression. Methods Based on data from multiple rounds of CA125 tests and transvaginal ultrasound (TVU) examinations conducted on 28,456 women in the PLCO Trial, time-dependent receiver-operating-characteristic curves (ROCs) and area-under-the-curves (tdAUCs) analyses were employed to identify the optimal CA125 cut-off values for OC screening. Participants were categorized into four CA125 trajectories: stable negative CA125 (CA125SN), loss of positive CA125 (CA125LP), stable positive CA125 (CA125SP), and gain of positive CA125 (CA125GP). The associations between different CA125 trajectories, trajectory-specific progression indicators, and OC risk were explored. The effectiveness of risk-stratified CA125 screening, incorporating CA125 trajectories, trajectory-specific progression, and TVU, was evaluated using hazard ratio and 95% confidence intervals [HR (95%CIs)], with adjustments for potential confounders. Results After a median follow-up of 14.8 years for OC incidence and 23.8 years for OC mortality, 250 OC cases and 218 OC deaths were identified. The tdAUC for 10-year OC incidence with CA125 was 0 . 663, with an optimal cut off value of 13.00 U/ml. Trajectory analyses showed that both CA125SP and CA125GP were significantly associated with increased risks of OC incidence [HRs (95%CIs): 2 . 00(1 .47–2. 73) and 3. 06(2 .25–4. 16)] and mortality [HRs (95%CIs):1.58(1.13–2.21) and 2.60(1.87–3.62)] compared to CA125SN. Trajectory-specific progression analyses identified relative velocity as the optimal progression indicators for both CA125SP and CA125GP (tdAUCs: 0.712 and 0.767), with optimal cut-off values of 9% and 32% per year, respectively. Positive progression was associated with significantly increased risks of OC incidence [HRs (95%CI): 7.26(4.00-13.17) and 3.83(1.96–7.51) CA125GP and CA125SP] and mortality [HRs (95%CI): 8 . 03(4 .15–15. 56) and 6. 04(2 .78–13. 14)] compared to negative progression. Optimized risk-stratified *Correspondence: Yubei Huang [yubei_huang@163.com](yubei_huang@163.com) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://](http://)[

FAQs

Why is CA125 screening effectiveness still debated in ovarian cancer?

The study notes that CA125 performance may be limited by an ineffective cutoff value and by insufficient consideration of CA125 trajectories and trajectory-specific progression.

How are CA125 trajectories defined in this research?

Participants are categorized into four trajectory groups: stable negative (CA125SN), loss of positive (CA125LP), stable positive (CA125SP), and gain of positive (CA125GP).

What screening approach is recommended based on the findings?

The study concludes that incorporating CA125 trajectories and trajectory-specific progression into screening protocols, together with transvaginal ultrasound, enhances identification of high-risk individuals and improves screening effectiveness.

Sep 21, 2026

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