2. Introduction – Endometrial Cancer

The goal orientation of the interdisciplinary S3 Guideline on Endometrial Carcinoma includes informing and advising women about diagnostics (clinical, imaging or surgical), the various therapeutic options (surgery, radiation, drug treatment) and, in particular, their temporal and modular combinations in the different stages of the disease, i.e. precancerous, early stages, advanced stages and palliative situation. In addition, the treatment of rare histological subtypes as well as hereditary variants is addressed.

The possibilities of preserving reproductive capacity while maintaining oncological safety, rehabilitation measures, aftercare, palliative therapy and psycho-oncological support will be discussed. This is necessary in the case of endometrial carcinoma, which changes the sexual life of women to a relevant extent, especially after the application of radiation. The recommendations are addressed to treating physicians, nursing professionals and medical partners involved in the treatment of patients with endometrial carcinoma. 

By reviewing the evidence, the optimal early detection and diagnosis of endometrial carcinoma and its precursors are elicited. There is potential here to improve early detection through consistent attention to appropriate symptoms. At the same time, there is very likely great potential to reduce unnecessary alarm and costs by avoiding diagnostic measures that do not make sense.

Evidence-based risk-adapted therapy can avoid unnecessary radical surgery and non-meaningful adjuvant radiotherapy and/or chemotherapy in women with low-risk endometrial cancer. On the one hand, this significantly reduces therapy-induced morbidity and increases the patients' quality of life. On the other hand, unnecessary costs are avoided. For women with endometrial carcinoma at high risk of recurrence the Guideline defines the optimal surgical radicality as well as the adjuvant chemotherapy and/or adjuvant radiotherapy that may be required. The evidence-based optimal use of the different therapeutic modalities should improve survival and quality of life of these patients. The S3 Guideline on Endometrial Cancer is intended to provide a basis for the work of certified gynecologic cancer centers. The quality indicators based on this Guideline are incorporated into the certification process of these centers. 

The interdisciplinary guideline on endometrial carcinoma (ICD-10 C54.1 [1]) covers patients with precancerous (ICD-10 N85.1 [1]) and invasive carcinomas of the endometrium. The recommendations of the guideline are aimed at physicians and healthcare professionals involved in the care of patients with endometrial carcinoma. These are primarily gynecologists, gynecologic oncologists, radiologists, pathologists, radiation oncologists, internal oncologists, psycho-oncologists, palliative care physicians, physical therapists, nurses, and are intended to inform general practitioners and urologists.

The guideline, in particular the patient version, is also aimed at all women suffering from endometrial carcinoma, and their relatives. The scope of application of the guideline includes the outpatient and inpatient care sector: The detection of early symptoms and follow-up care is largely the work of colleagues in private practice, while surgical treatment takes place in the inpatient sector. Radiation therapy and systemic drug therapy take place both in the area of the practicing colleagues and in the corresponding outpatient departments of larger hospitals. 

Further addressees of the guideline are:

• The medical-scientific professional societies and professional associations
• Women's advocacy groups (women's health organizations, patient and self-help organizations)
• Quality assurance institutions and projects at the federal and state level (e.g., Working Group of German Tumor Centers, etc.)
• Health policy institutions and decision-makers at the federal and state levels
• Payers

The methodology of the guideline program oncology provides for the assignment of grades of recommendation by the guideline authors within the framework of a formal consensus process. Accordingly, moderated nominal group processes or structured consensus conferences were conducted by the AWMF [2]. Within these processes, the recommendations were formally voted on by the voting mandate holders (see Chapter 1.9.2). The results of the respective votes (consensus strength) are assigned to the recommendations according to the categories in the table below. 

In the guideline, the level of evidence of the underlying studies and, in the case of recommendations, the strength of the recommendation (= degree of recommendation) are shown for all evidence-based statements and recommendations. With regard to the strength of the recommendation, three grades of recommendation are distinguished in this guideline (see table below), which are also reflected in the wording of the recommendations in each case. 

The degrees of recommendation express the degree of certainty that the expected benefit of the intervention outweighs the possible harm (net benefit) and that the expected positive effects reach a level that is relevant for patients. In the case of negative recommendations (shall not), safety is correspondingly expressed in terms of a lack of benefit or potential harm. In the graduation of recommendations, in addition to the results of the underlying studies, the clinical relevance of the effectiveness measures investigated in the studies, the observed effect sizes, the consistency of the study results, the applicability of the study results to the patient target group, the feasibility of implementation in everyday medical practice or ethical obligations, and patient preferences are taken into account [3], [2].

Recommendations are thematically related action guiding core sentences of the guideline, which are developed by the guideline group and agreed upon in formal consensus procedures.

 Table 5: Scheme of recommendation grading

Table 6: Determinations regarding consensus strength 

The German Cancer Aid provided the financial resources through the German Guideline Program in Oncology (GGPO). These funds were used for personnel costs, office supplies, literature procurement, and the consensus conferences. Working group meetings and conferences were held entirely online in 2020 and 2021. The guideline was developed with editorial independence from the funding organization. All members provided a written declaration of any conflicts of interest during the guideline process. The guideline group was asked to review the declarations of interest again before the first online consensus conference (March 08, 2021) and to provide any corrections or additions to the guideline secretariat. The disclosed conflicts of interest can be found in the guideline report for this guideline.

Obtaining declarations of interest 

Declarations of interest were obtained from all guideline group members at the beginning of the guideline project. The AWMF template „Declaration of Conflicts of Interest“ (see guideline report) was used for this purpose. All funding projects such as DFG and BMBF were declared. The guideline coordinator's declaration of interest was forwarded to the OL Office for review, and the others were reviewed for thematic relevance and relevance by the guideline coordinator. The AWMF classification of low, moderate, and high was used to assess the relevance of the conflicts of interest. Conflicts of interest of moderate relevance were seen as connections to industry-sponsored studies, third-party funded projects, and advisory boards that demonstrate a thematic relation to endometrial cancer. High relevance was seen for ownership interests (patents, shareholdings, etc.). The assessment revealed only conflicts of interest rated as low or moderate.

Dealing with conflicts of interest

Conflicts of interest of moderate relevance resulted in abstention from voting on the corresponding recommendations. In some cases, this was implemented electronically in such a way that all persons could vote, but subgroup analyses were subsequently performed with regard to persons with and without a moderate conflict of interest (outcome with participation of all vs. outcome with exclusion of persons with conflict of interest). Alternatively, however, abstention due to conflict of interest could be documented separately.

At the first consensus meeting on 08.03.2021 (video conference), it was unanimously agreed that mandate holders who led studies on endometrial cancer should not vote on the corresponding statements and recommendations. However, they could provide documents and further information and participate in the discussion. Third-party funding from industry and advisory boards should be indicated. The company name (third-party funding) should be mentioned. If third-party funding is disclosed, it should be made transparent which company it came from and what it was spent on. Individuals who have received industry-sponsored third-party funding related to endometrial cancer or who are members of an advisory board related to this indication should not vote on the statements and recommendations affected by this or subgroup analyses were performed here.

At this point, we would like to thank all collaborators for their exclusively voluntary work on the project!