HE4 in the Diagnostic Approach of Endometrial Cancer in Patients with Postmenopausal Bleeding, the METRODEC Protocol: Protocol for a Multicenter Prospective Study
Abstract
:1. Introduction
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- By endometrial biopsy (which is only of value if it finds a positive result in favor of a malignant lesion).
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- By hysteroscopy with endometrial biopsy or endometrial resection which is the most frequently performed surgery.
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- By hysterectomy from the outset in the case of very incapacitating metrorrhagia (less used method).
2. Methods and Design
2.1. Trial Design
2.2. Participating Centers
2.3. Eligibility Criteria
2.4. Inclusion Criteria
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- Patient with postmenopausal bleeding;
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- Patient requiring hysteroscopy or hysterectomy;
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- No objection from the patient to participate in the study.
2.5. Exclusion Criteria
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- Non-menopausal patient;
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- Patient under guardianship, curatorship, or deprived of her freedom;
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- Patient with proven metastases on imaging;
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- Patient with a macroscopically suspicious cervix;
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- Patient presenting an ovarian cyst or an associated adnexal pathology;
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- Patient contraindicated for surgical treatment (therefore not eligible for pathological analysis);
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- Patient who has already been treated with hormone therapy for breast cancer;
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- Patient who has already had surgery for this pathology, with a contributing anatomopathological result (we therefore include patients who would not benefit from an operative hysteroscopy after performing an endometrial biopsy that does not allow a positive result).
2.6. Materials
2.7. Outcome Measures
2.7.1. Primary Outcome
2.7.2. Secondary Outcomes
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- Other diagnostic parameters (specificity, positive predictive value (PPV), negative predictive value (NPV)) and the Area Under the Curve (AUC) of HE4 are assessed.
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- The optimal threshold of HE4 for the diagnosis of endometrial cancer are established with use of a Receiver Operating characteristic (ROC) curve.
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- The diagnostic capabilities of CA125 alone and in combination with HE4 are evaluated, as well as the Risk of Endometrial Malignancy (REM) and Risk of Endometrial Malignancy associated with Body Mass Index (REM-B) algorithms for the diagnosis of endometrial cancer.
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- (Estimation of sensitivity, specificity, PPV and NPV in the diagnosis of endometrial cancer for the CA125 biomarker and the REM and REM-B algorithms).
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- The existence of thresholds for HE4 and/or CA125 markers predictive of disease severity are established (FIGO stage).
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- We reassess the pathological threshold value of endometrial thickness on ultrasound.
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- The relationship between endometrial thickness on ultrasound and HE4 and CA125 marker values are assessed.
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- The diagnostic capabilities of HE4 and CA125 in subgroups of smoking patients and patients with renal failure are evaluated.
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- We identify potential confounding factors associated with the value of the HE4 marker like treatments, comorbidities (renal insufficiency, high Body Mass Index (BMI)), and other criteria that are collected in the medical files.
2.8. Sample Size
2.9. Statistical Methods
3. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
- Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 2015, 136, E359–E386. [Google Scholar] [CrossRef] [PubMed]
- Jamison, P.M.; Noone, A.-M.; Ries, L.A.G.; Lee, N.C.; Edwards, B.K. Trends in endometrial cancer incidence by race and histology with a correction for the prevalence of hysterectomy, SEER 1992 to 2008. Cancer Epidemiol. Biomark. Prev. 2013, 22, 233–241. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Weiderpass, E.; Antoine, J.; Bray, F.I.; Oh, J.-K.; Arbyn, M. Trends in corpus uteri cancer mortality in member states of the European Union. Eur. J. Cancer 2014, 50, 1675–1684. [Google Scholar] [CrossRef] [PubMed]
- Defossez, G.; Le Guyader-Peyrou, S.; Uhry, Z.; Grosclaude, P.; Colonna, M.; Dantony, E.; Delafosse, P.; Molinié, F.; Woronoff, A.S.; Bouvier, A.M.; et al. Volume 1–Tumeurs solides. In Estimations Nationales de l’incidence et de la Mortalité par Cancer en France Métropolitaine Entre 1990 et 2018; Santé publique: Saint-Maurice, France, 2019; 372p, Available online: http://www.santepubliquefrance.fr/ (accessed on 9 June 2020).
- Institut National Du Cancer. Cancer De L’endomètre: Synthèse Des Recommandations. [Internet]. Available online: https://www.e-cancer.fr (accessed on 19 May 2020).
- Hamdaoui, N.; Boubli, L. Management of side effects under hormonal replacement therapy in menopausal women: Abnormal uterine bleeding. Postmenopausal women management: CNGOF and GEMVi clinical practice guidelines. Gynecol. Obs. Fertil. Senol. 2021, 49, 474–484. [Google Scholar]
- Clarke, M.A.; Long, B.J.; Del Mar Morillo, A.; Arbyn, M.; Bakkum-Gamez, J.N.; Wentzensen, N. Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women: A Systematic Review and Meta-analysis. JAMA Intern. Med. 2018, 178, 1210–1222. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dochez, V.; Caillon, H.; Vaucel, E.; Dimet, J.; Winer, N.; Ducarme, G. Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review. J. Ovarian Res. 2019, 12, 28. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Institut National Du Cancer. Conduites à Tenir Initiales Devant Des Patientes Atteintes d’un Cancer Épithélial De l’ovaire. Synthèse, Novembre 2018; [Internet]. Available online: https://www.e-cancer.fr (accessed on 12 June 2019).
- Dochez, V.; Randet, M.; Renaudeau, C.; Dimet, J.; Le Thuaut, A.; Winer, N.; Thubert, T.; Vaucel, E.; Caillon, H.; Ducarme, G. Efficacy of HE4, CA125, Risk of Malignancy Index and Risk of Ovarian Malignancy Index to Detect Ovarian Cancer in Women with Presumed Benign Ovarian Tumours: A Prospective, Multicentre Trial. J. Clin. Med. 2019, 8, 1784. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Braun, M.M.; Overbeek-Wager, E.A.; Grumbo, R.J. Diagnosis and Management of Endometrial Cancer. Am. Fam. Physician 2016, 93, 468–474. [Google Scholar]
- Zamani, N.; Modares Gilani, M.; Mirmohammadkhani, M.; Sheikhhasani, S.; Mousavi, A.; Yousefi Sharami, S.R.; Akhavan, S.; Zamani, M.H.; Saffarieh, E. The Utility of CA125 and HE4 in Patients Suffering From Endometrial Cancer. Int. J. Women’s Health Reprod. Sci. 2019, 8, 95–100. [Google Scholar] [CrossRef]
- Angioli, R.; Miranda, A.; Aloisi, A.; Montera, R.; Capriglione, S.; De Cicco Nardone, C.; Terranova, C.; Plotti, F. A Critical Review on HE4 Performance in Endometrial Cancer: Where Are We Now? Tumour Biol. 2014, 35, 881–887. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Wang, X.; Qu, W.; Wang, J.; Jiang, S.-W. Comparison of serum human epididymis protein 4 and CA125 on endometrial cancer detection: A meta-analysis. Clin. Chim. Acta Janv. 2019, 488, 215–220. [Google Scholar] [CrossRef] [PubMed]
- Yılmaz, S.A.; Altınkaya, S.Ö.; Kerimoglu, Ö.S.; Tazegül Pekin, A.; Akyürek, F.; Ilhan, T.T.; Benzer, N.; Unlu, A.; Yuksel, H.; Cetin Celik, C. The role of human epididymis secretory protein E4 in patients with endometrial cancer and premalignant endometrial lesions. J. Obs. Gynaecol. 2017, 37, 58–63. [Google Scholar] [CrossRef] [PubMed]
- Degez, M.; Caillon, H.; Chauviré-Drouard, A.; Leroy, M.; Lair, D.; Winer, N.; Thubert, T.; Dochez, V. Endometrial cancer: A systematic review of HE4, REM and REM-B. Clin. Chim. Acta. Avr. 2021, 515, 27–36. [Google Scholar] [CrossRef] [PubMed]
- Qu, W.; Li, J.; Duan, P.; Tang, Z.; Guo, F.; Chen, H.; Zhu, X.; Jiang, S.-W. Physiopathological factors affecting the diagnostic value of serum HE4-test for gynecologic malignancies. Expert. Rev. Mol. Diagn. 2016, 16, 1271–1282. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dewan, R.; Dewan, A.; Hare, S.; Bhardwaj, M.; Mehrotra, K. Diagnostic Performance of Serum Human Epididymis Protein 4 in Endometrial Carcinoma: A Pilot Study. J. Clin. Diagn. Res. 2017, 11, XC01–XC05. [Google Scholar] [CrossRef] [PubMed]
- Antonsen, S.L.; Høgdall, E.; Christensen, I.J.; Lydolph, M.; Tabor, A.; Loft Jakobsen, A.; Fagö-Olsen, C.L.; Andersen, E.S.; Jochumsen, K.; Høgdall, C. HE4 and CA125 levels in the preoperative assessment of endometrial cancer patients: A prospective multicenter study (ENDOMET). Acta Obs. Gynecol. Scand. 2013, 92, 1313–1322. [Google Scholar] [CrossRef] [PubMed]
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Degez, M.; Caillon, H.; Chauviré-Drouard, A.; Leroy, M.; Lair, D.; Winer, N.; Thubert, T.; Le Floch, P.; Desroys du Roure, V.; Randet, M.; et al. HE4 in the Diagnostic Approach of Endometrial Cancer in Patients with Postmenopausal Bleeding, the METRODEC Protocol: Protocol for a Multicenter Prospective Study. Diagnostics 2021, 11, 1274. https://doi.org/10.3390/diagnostics11071274
Degez M, Caillon H, Chauviré-Drouard A, Leroy M, Lair D, Winer N, Thubert T, Le Floch P, Desroys du Roure V, Randet M, et al. HE4 in the Diagnostic Approach of Endometrial Cancer in Patients with Postmenopausal Bleeding, the METRODEC Protocol: Protocol for a Multicenter Prospective Study. Diagnostics. 2021; 11(7):1274. https://doi.org/10.3390/diagnostics11071274
Chicago/Turabian StyleDegez, Manon, Hélène Caillon, Anne Chauviré-Drouard, Maxime Leroy, David Lair, Norbert Winer, Thibault Thubert, Pauline Le Floch, Valérie Desroys du Roure, Mélanie Randet, and et al. 2021. "HE4 in the Diagnostic Approach of Endometrial Cancer in Patients with Postmenopausal Bleeding, the METRODEC Protocol: Protocol for a Multicenter Prospective Study" Diagnostics 11, no. 7: 1274. https://doi.org/10.3390/diagnostics11071274