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Prognostic value of CA125 kinetics, half-life, and nadir in the treatment of epithelial ovarian cancer: a systematic review and meta-analysis
  1. Ji Hyun Kim1,
  2. Hyun-Woong Cho2,
  3. Eun Young Park3,
  4. Kyung-Hee Han4,
  5. Eun Taeg Kim5,
  6. Jae-Kwan Lee6,
  7. Sang-Yoon Park1,
  8. Robert Armbrust7,
  9. Christina Fotopoulou8 and
  10. Myong Cheol Lim1
  1. 1Center for Gynecologic Cancer, National Cancer Center, Goyang, Korea (the Republic of)
  2. 2Obstetrics and Gynecology, Korea University Guro Hospital, Seoul, Korea (the Republic of)
  3. 3Biostatistics Collaboration Team, Research Core Center, National Cancer Center, Goyang, Korea (the Republic of)
  4. 4Department of Obstetrics and Gynecology, CHA Ilsan Medical Center, CHA University, Goyang, Korea (the Republic of)
  5. 5Department of Obstetrics and Gynecology, Kosin University College of Medicine, Busan, Korea (the Republic of)
  6. 6Department of Obstetrics and Gynecology, College of Medicine, Guro Hospital, Korea University, Seoul, Korea (the Republic of)
  7. 7Department of Gynecology, Charite University Hospital Berlin, Berlin, Germany
  8. 8Gynaecologic Oncology, Imperial College London Faculty of Medicine, London, UK
  1. Correspondence to Dr Myong Cheol Lim, Center for Gynecologic Cancer, National Cancer Center, Goyang 10287, Korea (the Republic of); gynlim{at}gmail.com

Abstract

Objective To investigate the prognostic value of cancer antigen 125 (CA125) related variables on progression free survival and overall survival in primary and recurrent ovarian cancers.

Method A comprehensive review of the Medline, Embase, and Cochrane Library databases was conducted to identify relevant literature on survival outcomes according to the ELIMination Rate Constant K (KELIM), Gynecologic Cancer InterGroup (GCIG) CA125 response criteria, CA125 half-life, and CA125 nadir levels during first line or later line chemotherapy. The search included articles published before February 2023. Cut-off values determining the favorable/unfavorable score of each study were extracted, and pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed using a random effects model to identify the relationship between survival outcomes of the favorable/unfavorable groups, which was determined by an individual model using CA125 kinetics.

Results A total of 27 studies with 14 444 patients with epithelial ovarian cancer were included in this meta-analysis. In primary ovarian cancer, a favorable KELIM score, determined by individual modeled cut-off values, was associated with a significant progression free survival (HR 0.53, 95% CI 0.45 to 0.62) and overall survival (HR 0.51, 95% CI 0.43 to 0.62) benefit in the primary setting. The favorable KELIM scored group also correlated with a better progression free survival (HR 0.54, 95% CI 0.47 to 0.62) in relapsed disease. We failed to demonstrate a better prognostic value of the GCIG response criteria and the CA125 half-life for progression free survival and overall survival.

Conclusion Novel chemotherapy response scores, such as KELIM, may be more clinically relevant than other prognostic models using CA125 kinetics, being directly associated with a more favorable survival in both the primary and relapsed setting in patients with epithelial ovarian cancer.

Study registration The systemic review and meta-analysis were registered in PROSPERO (CRD42023385512).

  • Ovarian Cancer
  • Carcinoma, Ovarian Epithelial

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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Footnotes

  • JHK and H-WC are joint first authors.

  • Contributors MCL accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. JHK and HWC contributed equally to this work. Conception of study: JHK, HWC, and MCL. Design and development: JHK, HWC, EYP, and MCL. Data collection: JHK, HWC, EYP, KHH, and ETK. Data analysis and interpretation: JHK, H-WC, EYP, CF, and MCL. Preparation of tables and figures: JHK, HWC, and EYP. Initial draft of manuscript: JHK, HWC, EYP, KHH, and ETK. Manuscript review: JHK, HWC, K-HH, ETK, JKL, SYP, RA, CF, and MCL. Final approval of manuscript: all authors.

  • Funding This research was funded by the Korea Health Industry Development Institute (grant No HA23C0533) and National Cancer Center Korea (NCC2110790, NCC2212770).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.