HE4 in the Diagnostic Approach of Endometrial Cancer in Patients With Postmenopausal Bleeding (METRODEC)

Multicenter Prospective Study Evaluating the Interest of HE4 in the Diagnostic Approach of Endometrial Cancer in Patients With Postmenopausal Bleeding

This study aims to explore the sensitivity of an innovative marker, HE4, in the diagnosis approach of endometrial cancer in case of postmenopausal bleedings.

Study Overview

• Status: Recruiting
• Conditions: Endometrial Neoplasms; Uterine Hemorrhage; Postmenopause; Cancer Biomarker; CA 125 Antigen
• Intervention / Treatment: Other: Patients with Post menopausal bleeding; Diagnostic test: CA125 and HE4 assays

Detailed Description

Endometrial cancer is the most common pelvic gynecological cancer in France, ranking 5th among cancers in women in terms of incidence.

The most frequent symptom is post-menopausal bleeding and is one of the primary reasons for consultation in gynecological emergencies.

The diagnosis of endometrial cancer is made by histological analysis of endometrial tissue taken during a surgical intervention. The latter is mostly reassuring.

These interventions are often performed in mild situations and there is currently no element to be sufficiently reassuring to avoid surgery.

At present, there is no biological marker used in current practice. In the population of patients with post-menopausal bleeding requiring surgical exploration for diagnosis, the pathology results are often reassuring. These procedures could have been avoided, especially as these patients often have numerous co-morbidities and these surgeries are therefore more risky. The appearance of a new tumour marker could be useful in the management of these patients and avoid many unnecessary and risky surgeries

This study aims to explore the sensitivity of an innovative marker, HE4, in the diagnosis approach of endometrial cancer in case of postmenopausal bleedings.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Vincent DOCHEZ, MD; Phone Number: 33 2 40 08 78 00; Email: vincent.dochez@chu-nantes.fr

Study Locations

• France
  • Loire-Atlantique
    • Saint-Nazaire, Loire-Atlantique, France, 44606
      • Recruiting
      • Saint-Nazaire Hospital
      • Principal Investigator: Mélanie RANDET, MD
  • Vendee
    • La Roche-sur-Yon, Vendee, France, 85925
      • Recruiting
      • Vendee Hospital Center
      • Principal Investigator: Guillaume DUCARME, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Any patient with postmenopausal bleeding who is to undergo hysteroscopy or hysterectomy will have an additional blood tube taken during her pre-operative blood work-up for the measurement of the serum markers HE4 and CA125 after she has indicated that she does not wish to participate in the study

Description

Inclusion Criteria:

• Patient with postmenopausal bleeding
• Patient requiring hysteroscopy or hysterectomy
• No objection from the patient to participate in the study

Exclusion Criteria:

• Non-menopausal patient
• Patient under guardianship, curatorship or deprived of her freedom
• Patient with proven metastases on imaging
• Patient with a macroscopically suspicious cervix
• Patient presenting an ovarian cyst or an associated adnexal pathology
• Patient contraindicated for surgical treatment (therefore not eligible for pathological analysis)
• Patient who has already been treated with hormone therapy for breast cancer
• Patient who has already had surgery for this pathology, with a contributing anatomopathological result (we will therefore include patients who would not benefit from an operative hysteroscopy after performing a cornier® pipelle that does not allow a positive result)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the sensitivity of the HE4 marker in patients with postmenopausal bleeding in the diagnosis of endometrial cancer	The HE4 assays will be performed using the electrochemiluminescence (ECL) technique on Cobas Pro module E801, Roche Diagnostics. The HE4 assay is based on a sandwich-type electrochemiluminescence method. The HE4 assay with the Roche Diagnostics Elecsys reagent has been standardized against the Fujirebo Diagnostics HE4 EIA method. Positive/negative HE4 result for the estimation of the sensitivity of HE4 in the diagnosis of endometrial cancer. The commonly accepted threshold for ovarian cancer management of 140pmol/l in postmenopausal patients should be used. The gold standard for endometrial cancer is the pathological result (absence/presence of cancer) of the sample taken.	Until the pathological results (About 10-15 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess other diagnostic parameters (specificity, PPV, NPV) of HE4	ROC curve for the HE4 marker in the diagnosis of endometrial cancer.	Until the pathological results (About 10-15 days)
Establish the optimal threshold of HE4 for the diagnosis of endometrial cancer (use of an ROC curve)	Search for the threshold with the best specificity of HE4 in the diagnosis of endometrial cancer	Until the pathological results (About 10-15 days)
Evaluate the diagnostic capabilities of CA125 alone and in combination with HE4, as well as the REM and REM-B algorithms for the diagnosis of endometrial cancer	Estimation of sensitivity, specificity, PPV and NPV in the diagnosis of endometrial cancer for the CA125 biomarker and the REM and REM B algorithms	Until the pathological results (About 10-15 days)
Establish the existence of thresholds for HE4 and/or CA125 markers predictive of disease severity (FIGO stage)	Search for HE4 and CA125 marker thresholds to assess disease severity by FIGO stage	Until the results of the extension assessment in the event of proven endometrial cancer (1 month)
Reassess the pathological threshold value of endometrial thickness on ultrasound	Search for the pathological threshold of endometrial thickness in the diagnosis of endometrial cancer	Until the pathological results (About 10-15 days)
Assess the relationship between endometrial thickness on ultrasound and HE4 and CA125 marker values	Estimation of the relationship between CA125 and HE4 markers and endometrial thickness on ultrasound	Until the pathological results (About 10-15 days)
To evaluate the diagnostic capabilities of HE4 and CA125 in subgroups of smoking patients and patients with renal failure	Estimation of sensitivity, specificity, PPV and NPV in the diagnosis of endometrial cancer for HE4 and CA125 in patients with active smoking and/or renal failure	Until the pathological results (About 10-15 days)
Identify potential confounding factors associated with the value of the HE4 marker like treatments, comorbidities (renal insufficiency, high BMI) and others criteria that are collected in the medical files	Analyses of variables measured at inclusion that may influence the value of the HE4 marker.	Until the pathological results (About 10-15 days)

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Collaborators: Roche Diagnostics

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2021
• Primary Completion (Anticipated): August 1, 2022
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: April 13, 2021
• First Submitted That Met QC Criteria: April 29, 2021
• First Posted (Actual): April 30, 2021

Study Record Updates

• Last Update Posted (Actual): September 17, 2021
• Last Update Submitted That Met QC Criteria: September 10, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: HE4; CA125; Endometrial cancer; Human epididymis protein 4; Post-menopausal bleeding
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Hemorrhage; Endometrial Neoplasms; Uterine Hemorrhage
• Other Study ID Numbers: RC21_0166

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No