Background: Ovarian, fallopian tube, and primary peritoneal cancers often share clinical characteristics and are typically diagnosed at advanced stages due to nonspecific symptoms. The utility of tumor markers, particularly CA125 and HE4, in the diagnosis and follow-up of these cancers remains an area of active investigation. Objectives: The CEEGOG (Central and Eastern European Gynecologic Oncology Group) OX-01 study aimed to evaluate HE4's role alongside CA125 in follow-up for advanced-stage ovarian, fallopian tube, and primary peritoneal cancers. It assessed the potential for detecting recurrence using marker elevation and imaging methods, examining the necessity of dynamic monitoring and current cut-off values' accuracy for early relapse detection. Methods: In this multicenter prospective cohort study, 117 eligible patients with Stage III-IV cancers were included. Patients had elevated CA125 or HE4 at diagnosis and achieved complete remission after first-line treatment. HE4 and CA125 levels were monitored every 3-4 months in the first two years and every six months thereafter. CT scans were performed if markers exceeded set thresholds or increased by over 20%. Results: During a median follow-up of 13.7 months, 73% of patients relapsed. Median HE4 levels were significantly higher in relapsed patients. A 10 IU/mL increase from baseline in CA125 had a sensitivity of 83% and specificity of 93%, while a 15 pmol/L increase in HE4 had a sensitivity of 74% and specificity of 92% for predicting relapse up to three months before CT scan detection. Conclusions: The study found that dynamic changes in HE4 and CA125 levels, rather than predefined cut-off values, are crucial for early relapse detection. These markers may offer a significant lead time over imaging, potentially enabling earlier intervention. Further research is needed to validate these findings.

Department of Gynecologic Oncology National Cancer Institute M Sklodowska Curie Memorial Institute 31 115 Cracow Poland

Department of Gynecological Oncology St Elizabeth Cancer Institute 811 08 Bratislava Slovakia

Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents Pomeranian Medical University in Szczecin 70 204 Szczecin Poland

Department of Gynecology and Gynecologic Oncology Kliniken Essen Mitte 45136 Essen Germany

Department of Gynecology and Obstetrics Faculty of Medicine in Pilsen Charles University 306 05 Pilsen Czech Republic

Department of Gynecology and Obstetrics Faculty of Medicine in Pilsen University Hospital Pilsen Charles University 323 00 Pilsen Czech Republic

Department of Gynecology and Obstetrics Jihlava Hospital 586 01 Jihlava Czech Republic

Department of Gynecology and Obstetrics KNTB a s Zlin 762 75 Zlin Czech Republic

Department of Internal Medicine Hematology and Oncology University Hospital Brno and Medical Faculty Masaryk University 625 00 Brno Czech Republic

Department of Obstetrics and Gynecology University Hospital Brno and Medical Faculty Masaryk University 625 00 Brno Czech Republic

Department of Obstetrics Gynecology and Neonatology 1st Faculty of Medicine Charles University and General University Hospital Prague 128 08 Prague Czech Republic

Department of Oncology and Radiology Danylo Halytsky Lviv National Medical University 79010 Lviv Ukraine

Department of Oncology Faculty Hospital Trencin Faculty of Healthcare Alexander Dubcek University of Trencin 911 06 Trencin Slovakia

Department of Oncology KNTB a s Zlin 762 75 Zlin Czech Republic

Gynecologic Oncology Division NN Alexandrov National Cancer Centre 223040 Minsk Belarus

Gynecological Oncology Department Lower Silesian Oncology Pulmonology and Hematology Center Wroclaw Medical University 53 413 Wroclaw Poland

Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

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