Geburtshilfe Frauenheilkd 2023; 83(08): 963-995
DOI: 10.1055/a-2066-2068
GebFra Science
Guideline/Leitlinie

Endometrial Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry Number 032/034-OL, September 2022) – Part 2 with Recommendations on the Therapy of Precancerous Lesions and Early-stage Endometrial Cancer, Surgical Therapy, Radiotherapy and Drug-based Therapy, Follow-up Care, Recurrence and Metastases, Psycho-oncological Care, Palliative Care, Patient Education, and Rehabilitative and Physiotherapeutic Care

Article in several languages: English | deutsch
Günter Emons
1   Universitätsmedizin Göttingen, Klinik für Gynäkologie und Geburtshilfe, Göttingen, Germany
,
Eric Steiner
2   Frauenklinik GPR Klinikum Rüsselsheim am Main, Rüsselsheim, Germany
,
Dirk Vordermark
3   Universität Halle (Saale), Radiotherapie, Halle (Saale), Germany
,
Christoph Uleer
4   Facharzt für Frauenheilkunde und Geburtshilfe, Hildesheim, Germany
,
Kerstin Paradies
5   Konferenz onkologischer Kranken- und Kinderkrankenpfleger (KOK), Hamburg, Germany
,
Clemens Tempfer
6   Frauenklinik der Ruhr-Universität Bochum, Bochum/Herne, Germany
,
Stefan Aretz
7   Institut für Humangenetik, Universität Bonn, Zentrum für erbliche Tumorerkrankungen, Bonn, Germany
,
Wolfgang Cremer
8   Praxis für Frauenheilkunde Hamburg, Hamburg, Germany
,
Volker Hanf
9   Frauenklinik Nathanstift – Klinikum Fürth, Fürth, Germany
,
Peter Mallmann
10   Uniklinik Köln, Frauenheilkunde, Köln, Germany
,
Olaf Ortmann
11   Universität Regensburg, Fakultät für Medizin, Klinik für Frauenheilkunde und Geburtshilfe, Regensburg, Germany
,
Thomas Römer
12   Evangelisches Klinikum Köln Weyertal, Gynäkologie Köln, Köln, Germany
,
Rita K. Schmutzler
13   Universitätsklinikum Köln, Zentrum Familiärer Brust- und Eierstockkrebs, Köln, Germany
,
Lars-Christian Horn
14   Universitätsklinikum Leipzig, Institut für Pathologie, Leipzig, Germany
,
Stefan Kommoss
15   Universitätsklinikum Tübingen, Universitätsfrauenklinik Tübingen, Tübingen, Germany
,
Sigurd Lax
16   Institut für Pathologie, LKH Graz Süd-West, Graz, Austria
,
Elisa Schmoeckel
17   Pathologisches Institut der LMU München, München, Germany
,
Theresa Mokry
18   Universitätsklinikum Heidelberg, Diagnostische und Interventionelle Radiologie, Heidelberg, Germany
,
Dieter Grab
19   Universitätsklinikum Ulm, Frauenheilkunde und Geburtshilfe, Ulm, Germany
,
Michael Reinhardt
20   Klinik für Nuklearmedizin, Pius Hospital Oldenburg, Oldenburg, Germany
,
Verena Steinke-Lange
21   MGZ – Medizinisch Genetisches Zentrum München, München, Germany
22   Medizinische Klinik und Poliklinik IV, LMU München, München, Germany
,
Sara Y. Brucker
15   Universitätsklinikum Tübingen, Universitätsfrauenklinik Tübingen, Tübingen, Germany
,
Ludwig Kiesel
23   Universitätsklinikum Münster, Frauenklinik A Schweitzer Campus 1, Münster, Germany
,
Ralf Witteler
23   Universitätsklinikum Münster, Frauenklinik A Schweitzer Campus 1, Münster, Germany
,
Markus C. Fleisch
24   Helios, Universitätsklinikum Wuppertal, Landesfrauenklinik, Wuppertal, Germany
,
Heinrich Prömpeler †,
Michael Friedrich
26   Helios Klinikum Krefeld, Klinik für Frauenheilkunde und Geburtshilfe, Krefeld, Germany
,
Stefan Höcht
27   XCare, Praxis für Strahlentherapie Saarlouis, Saarlouis, Germany
,
Werner Lichtenegger
28   Universitätsmedizin Berlin, Frauenklinik Charité, Campus Virchow-Klinikum, Berlin, Germany
,
Michael Mueller
29   Universitätsklinik für Frauenheilkunde, Inselspital Bern, Bern, Switzerland
,
Ingo Runnebaum
30   Universitätsklinikum Jena, Frauenklinik, Jena, Germany
,
Petra Feyer
31   Vivantes Klinikum Neukölln, Klinik für Strahlentherapie und Radioonkologie, Berlin, Germany
,
Volker Hagen
32   Klinik für Innere Medizin II, St.-Johannes-Hospital Dortmund, Dortmund, Germany
,
Ingolf Juhasz-Böss
33   Universitätsklinikum Freiburg, Gynäkologie Freiburg, Freiburg, Germany
,
Anne Letsch
34   Universitätsklinikum Schleswig Holstein, Campus Kiel, Innere Medizin, Kiel, Germany
,
Peter Niehoff
35   Strahlenklinik, Sana Klinikum Offenbach, Offenbach, Germany
,
Alain Gustave Zeimet
36   Medizinische Universität Innsbruck, Universitätsklinik für Gynäkologie und Geburtshilfe, Innsbruck, Austria
,
Marco Johannes Battista
37   Universitätsmedizin Mainz, Poliklinik für Geburtshilfe und Frauengesundheit, Mainz, Germany
,
Edgar Petru
38   Med. Univ. Graz, Frauenheilkunde, Graz, Austria
,
Simone Widhalm
39   Semi-Colon, Mönchengladbach, Germany
,
Birgitt van Oorschot
40   Universitätsklinikum Würzburg, Interdisziplinäres Zentrum Palliativmedizin, Würzburg, Germany
,
Joan Elisabeth Panke
41   Medizinischer Dienst des Spitzenverbandes Bund der Krankenkassen e. V. Essen, Essen, Germany
,
Joachim Weis
42   Albert-Ludwigs-Universität Freiburg, Medizinische Fakultät, Tumorzentrum Freiburg – CCCF, Freiburg, Germany
,
Timm Dauelsberg
43   Universitätsklinikum Freiburg, Klinik für Onkologische Rehabilitation, Freiburg, Germany
,
Heidemarie Haase
44   Frauenselbsthilfe, Bonn, Germany
,
Matthias W. Beckmann
45   Universitätsklinikum Erlangen, Frauenklinik, Erlangen, Germany
,
Sebastian Jud
46   Mutterhaus der Borromäerinnen, Trier, Germany
,
Edward Wight
47   Frauenklinik des Universitätsspitals Basel, Basel, Switzerland
,
Franz-Josef Prott
48   Facharzt für Radiologie und Strahlentherapie, Wiesbaden, Wiesbaden, Germany
,
Oliver Micke
49   Franziskus Hospital Bielefeld, Klinik für Strahlentherapie und Radioonkologie, Bielefeld, Germany
,
Werner Bader
50   Klinikum Bielefeld Mitte, Zentrum für Frauenheilkunde, Bielefeld, Germany
,
Nicola Reents
39   Semi-Colon, Mönchengladbach, Germany
,
Ulla Henscher
51   Physio-Akademie, Hannover, Germany
,
Reina Tholen †,
Miriam Schallenberg
44   Frauenselbsthilfe, Bonn, Germany
,
Nils Rahner
53   Amedes Group Bonn, Bonn, Germany
,
Doris Mayr
54   LMU München, Pathologisches Institut, München, Germany
,
Michael Kreißl
55   Universität Magdeburg, Medizinische Fakultät, Universitätsklinik für Radiologie und Nuklearmedizin, Germany
,
Katja Lindel
56   Städtisches Klinikum Karlsruhe, Karlsruhe, Germany
,
Alexander Mustea
57   Universitätsklinikum Bonn, Zentrum Gynäkologie und gynäkologische Onkologie, Bonn, Germany
,
Vratislav Strnad
58   Universitätsklinikum Erlangen, Brustzentrum Franken, Erlangen, Germany
,
Ute Goerling
59   Universitätsmedizin Berlin, Campus Charité Mitte, Charité Comprehensive Cancer Center, Berlin, Germany
,
Gerd J. Bauerschmitz
1   Universitätsmedizin Göttingen, Klinik für Gynäkologie und Geburtshilfe, Göttingen, Germany
,
Jan Langrehr
60   Martin-Luther-Krankenhaus, Klinik für Allgemein-, Gefäß- und Viszeralchirurgie, Berlin, Germany
,
Joseph Neulen
61   Uniklinik RWTH Aachen, Klinik für Gynäkologische Endokrinologie und Reproduktionsmedizin, Aachen, Germany
,
Uwe Andreas Ulrich
62   Martin-Luther-Krankenhaus, Johannesstift Diakonie, Gynäkologie, Berlin, Germany
,
Monika J. Nothacker
63   AWMF, AWMF-IMWi, Berlin, Germany
,
Susanne Blödt
63   AWMF, AWMF-IMWi, Berlin, Germany
,
Markus Follmann
64   Deutsche Krebsgesellschaft, Office des Leitlinienprogramms Onkologie, Berlin, Germany
,
Thomas Langer
64   Deutsche Krebsgesellschaft, Office des Leitlinienprogramms Onkologie, Berlin, Germany
,
Gregor Wenzel
64   Deutsche Krebsgesellschaft, Office des Leitlinienprogramms Onkologie, Berlin, Germany
,
Sylvia Weber
1   Universitätsmedizin Göttingen, Klinik für Gynäkologie und Geburtshilfe, Göttingen, Germany
,
Saskia Erdogan
1   Universitätsmedizin Göttingen, Klinik für Gynäkologie und Geburtshilfe, Göttingen, Germany
› Author Affiliations
 

Abstract

Summary The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020. All statements, recommendations and background texts were reviewed and either confirmed or amended. New statements and recommendations were included where necessary.

Aim The use of evidence-based risk-adapted therapies to treat low-risk women with endometrial cancer prevents unnecessarily radical surgery and avoids non-beneficial adjuvant radiation therapy and/or chemotherapy. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimum level of radical surgery and indicates whether chemotherapy and/or adjuvant radiation therapy is necessary. This should improve the survival rates and quality of life of these patients. The S3-guideline on endometrial cancer and the quality indicators based on the guideline aim to provide the basis for the work of certified gynecological cancer centers.

Methods The guideline was first compiled in 2018 in accordance with the requirements for S3-level guidelines and was updated in 2022. The update included an adaptation of the source guidelines identified using the German Instrument for Methodological Guideline Appraisal (DELBI). The update also used evidence reviews which were created based on selected literature obtained from systematic searches in selected literature databases using the PICO process. The Clinical Guidelines Service Group was tasked with carrying out a systematic search and assessment of the literature. Their results were used by interdisciplinary working groups as a basis for developing suggestions for recommendations and statements which were then modified during structured online consensus conferences and/or additionally amended online using the DELPHI process to achieve a consensus.

Recommendations Part 2 of this short version of the guideline provides recommendations on the treatment of precancerous lesions and early-stage endometrial cancer, surgical treatment, radiotherapy and drug-based therapy, follow-up, recurrence, and metastasis of endometrial cancer as well as the state of psycho-oncological care, palliative care, patient education, rehabilitative and physiotherapeutic care.


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I  Guideline Information

Guidelines program of the DGGG, OEGGG and SGGG

For information on the guidelines program, please refer to the end of the guideline.


#

Citation format

Endometrial Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry Number 032/034-OL, September 2022) – Part 2 with Recommendations on the Therapy of Precancerous Lesions and Early-stage Endometrial Cancer, Surgical Therapy, Radiotherapy and Drug-based Therapy, Follow-up Care, Recurrence and Metastases, Psycho-oncological Care, Palliative Care, Patient Education, and Rehabilitative and Physiotherapeutic Care. Geburtsh Frauenheilk 2023; 83: 963–995


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Guideline documents

The complete German-language long version of this guideline together with a list of the conflicts of interest of all the authors are available on the homepage of the AWMF: https://register.awmf.org/de/leitlinien/detail/032-034OL


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Guideline authors

See [Tables 1] and [2].

Table 1 Lead and/or coordinating guideline authors.

Coordinator:

Prof. Dr. Günter Emons; Göttingen

Co-coordinator:

Prof. Dr. Eric Steiner; Rüsselsheim

Editorial team:

Saskia Erdogan, M. A.; Göttingen

Sylvia Weber; Göttingen

Table 2 Contributing guideline authors.

Contributing professional societies and organizations (in alphabetical order)

Persons

1 † 04.02.2021; 2 † 04.06.2022

* These persons contributed significantly to the compilation of the guideline. They did not participate in voting on recommendations and statements.

Gynecological Endoscopy Working Group of the DGGG [AG Endoskopische Gynäkologie der DGGG]

Prof. Dr. Ingo Runnebaum

Prof. Dr. Uwe Ulrich

AGO Study Group

Prof. Dr. Stefan Kommoss

Association of German Tumor Centers [Arbeitsgemeinschaft Deutscher Tumorzentren e. V.] (ADT)

Prof. Dr. Olaf Ortmann

Gynecological Oncology Working Group of the DGGG and DKG [Arbeitsgemeinschaft Gynäkologische Onkologie der DGGG und DKG] (AGO)

Prof. Dr. Peter Mallmann

Prof. Dr. Ingolf Juhasz-Böss

Working Group of the DKG: Conference of Oncological Nursing and Pediatric Nursing [Arbeitsgemeinschaft Konferenz Onkologische Kranken- und Kinderkrankenpflege in der DKG] (KOK)

Kerstin Paradies

Palliative Medicine Working Group of the German Cancer Society [Arbeitsgemeinschaft Palliativmedizin der Deutschen Krebsgesellschaft e. V.] (APM)

Prof. Dr. Birgitt van Oorschot

Dr. Joan E. Panke

Prevention and Integrative Oncology Working Group of the DKG [Arbeitsgemeinschaft Prävention und integrative Medizin in der Onkologie der Deutschen Krebsgesellschaft] (PRiO)

Prof. Dr. Volker Hanf

Prof. Dr. Oliver Micke

Radiological Oncology Working Group [Arbeitsgemeinschaft Radiologische Onkologie] (ARO)

Prof. Dr. Stefan Höcht

Prof. Dr. Vratislav Strnad

Working Group for Supportive Measures in Oncology [Arbeitsgemeinschaft Supportive Maßnahmen in der Onkologie] (AGSMO)

Prof. Dr. Petra Feyer

DKG Working Group for Hereditary Tumor Disease [Arbeitsgemeinschaft erbliche Tumorerkrankungen in der DKG] (AET)

Prof. Dr. Stefan Aretz

Prof. Dr. Rita Schmutzler

German Psycho-oncology Working Group [Arbeitsgemeinschaft für Psychoonkologie in der DKG] (PSO)

Prof. Dr. Joachim Weis

PD Dr. Ute Goerling

Working Group for Oncological Rehabilitation and Social Medicine [Arbeitsgemeinschaft für onkologische Rehabilitation und Sozialmedizin] (AGORS)

Dr. Timm Dauelsberg

Medical Oncology Working Group of the DKG [Arbeitsgemeinschaft internistische Onkologie der Deutschen Krebsgesellschaft e. V.] (AIO)

Dr. Volker Hagen

Prof. Dr. Anne Letsch

Federal Association of German Radiotherapists [Berufsverband der Deutschen Strahlentherapeuten e. V.] (BVDST)

Prof. Dr. Peter Niehoff

Prof. Dr. Franz-Josef Prott

Professional Association of Gynecologists [Berufsverband der Frauenärzte] (BVF)

Dr. Wolfgang Cremer

Professional Association of Gynecological Oncologists in Private Practice in Germany [Berufsverband niedergelassener Gynäkologischer Onkologen in Deutschland] (BNGO)

Dr. Christoph Uleer

Contributing experts (without a vote)

PD Dr. Marco J. Battista

PD Dr. Dr. Gerd J. Bauerschmitz

Prof. Dr. Markus Fleisch

Prof. Dr. Sigurd Lax

Prof. Dr. Clemens Tempfer

Contributing experts (without a vote)

Dr. Barbara Zimmer*

Ilkas Luckas*

Federal Association of Senior Physicians in Gynecology and Obstetrics [Bundesarbeitsgemeinschaft Leitender Ärztinnen und Ärzte in der Frauenheilkunde und Geburtshilfe] (BLFG)

Prof. Dr. Michael Friedrich

Professional Association of German Pathologists [Bundesverband Deutscher Pathologen e. V.] (BDP)

Prof. Dr. Lars-Christian Horn

Prof. Dr. Doris Mayr

German Society for General and Visceral Surgery [Deutsche Gesellschaft für Allgemein- u. Viszeralchirurgie] (DGAV)

Prof. Dr. Jan Langrehr

German Society of Endocrinology [Deutsche Gesellschaft für Endokrinologie e. V.] (DGE)

Prof. Dr. Matthias W. Beckmann

PD Dr. Sebastian Jud

German Society of Gynecology and Obstetrics [Deutsche Gesellschaft für Gynäkologie und Geburtshilfe e. V.] (DGGG)

Prof. Dr. Sara Y. Brucker

German Society for Gynecological Endocrinology and Fertility [Deutsche Gesellschaft für Gynäkologische Endokrinologie und Fertilität]

Prof. Dr. Ludwig Kiesel

Dr. Ralf Witteler

German Society of Human Genetics [Deutsche Gesellschaft für Humangenetik] (GfH)

Dr. Verena Steinke-Lange

Dr. Nils Rahner

German Society of Hematology and Medical Oncology [Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e. V.] (DGHO)

Prof. Dr. Anne Letsch

Dr. Volker Hagen

German Society of Nuclear Medicine [Deutsche Gesellschaft für Nuklearmedizin e. V.] (DGN)

Prof. Dr. Michael J. Reinhardt

Prof. Dr. Michael Kreißl

German Society for Palliative Medicine [Deutsche Gesellschaft für Palliativmedizin e. V.] (DGP)

Prof. Dr. Anne Letsch

German Society of Pathology [Deutsche Gesellschaft für Pathologie e. V.] (DGP)

Prof. Dr. Lars-Christian Horn

Prof. Dr. Doris Mayr

German Society for Radiation Oncology [Deutsche Gesellschaft für Radioonkologie e. V.] (DEGRO)

Prof. Dr. Dirk Vordermark

Prof. Dr. Katja Lindel

German Society for Ultrasound in Medicine [Deutsche Gesellschaft für Ultraschall in der Medizin e. V.] (DEGUM)

Prof. Dr. Dieter Grab

Prof. Dr. Werner Bader

German Society for Ultrasound in Medicine [Deutsche Gesellschaft für Ultraschall in der Medizin e. V.] (DEGUM)

Prof. Dr. Heinrich Prömpeler1

German Menopause Society [Deutsche Menopause Gesellschaft] (DMG)

Prof. Dr. Thomas Römer

Prof. Dr. Joseph Neulen

German Roentgen Society [Deutsche Röntgengesellschaft e. V.]

Dr. Theresa Mokry

Self-help Group for Women after Cancer [Frauenselbsthilfe Krebs e. V.] (FSH)

Heidemarie Haase

Miriam Schallenberg

Northeast German Society of Gynecological Oncology [Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie] (NOGGO)

Prof. Dr. Werner Lichtenegger

Prof. Dr. Alexander Mustea

Swiss Society of Gynecology and Obstetrics [Schweizerische Gesellschaft für Gynäkologie und Geburtshilfe] (SGGG)

Prof. Dr. Michael D. Mueller

PD Dr. Edward Wight

Semi-Colon, Family Support for Persons with Bowel Cancer [Semi-Colon, Familienhilfe Darmkrebs e. V.]

Simone Widhalm

Nicola Reents

Central Association of Physiotherapists [Zentralverband der Physiotherapeuten/Krankengymnasten] (ZVK)

Ulla Henscher

Reina Tholen2

Austrian Society of Gynecology and Obstetrics [Österreichische Gesellschaft für Gynäkologie und Geburtshilfe] (OEGGG)

Prof. Dr. Alain-Gustave Zeimet

Prof. Dr. Edgar Petru

The guideline was moderated by Dr. Susanne Blödt, Dr. Monika Nothacker, Dr. Markus Follmann and Thomas Langer (AWMF-certified guideline advisors/moderators).


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Abbreviations

EC: expert consensus
ST: statement
 


#
#

II  Guideline Application

Purpose and objectives

The most important reason for compiling this interdisciplinary guideline is the unchangingly high epidemiological importance of endometrial cancer and the associated burden of disease.

New data on pathological/molecular classifications and adjuvant and palliative treatments have been published in recent years, which made it necessary to update the guideline. The use of evidence-based risk-adapted therapies to treat women with low-risk endometrial cancer prevents unnecessarily radical surgery and avoids non-beneficial adjuvant radiation therapy and/or chemotherapy. This reduces treatment-induced morbidity, improves patientsʼ quality of life, and avoids unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimum level of radical surgery and indicates whether chemotherapy and/or adjuvant radiation therapy is necessary. An evidence-based optimum use of different treatment modalities should improve the survival rates and quality of life of these patients.


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Target user group/target audience

The recommendations in this guideline are aimed at all physicians and members of professions involved in the care of patients with endometrial cancer. They primarily include gynecologists, general practitioners, radiologists, pathologists, radio-oncologists, hematologists and medical oncologists, psycho-oncologists, specialists for palliative medicine and nursing staff.

Other groups for whom this guideline was developed include:

  • scientific medical societies and professional organizations;

  • advocacy groups for women (womenʼs health organizations, patient and self-help organizations);

  • quality assurance institutions and projects at federal and Länder levels (e.g., the Association of German Tumor Centers, etc.);

  • health policy institutions and decision-makers at federal and Länder levels;

  • funding agencies.


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Adoption and period of validity

The validity of this guideline was confirmed by the executive boards/heads of the participating professional societies, working groups, organizations, associations as well as by the boards of the DGGG, SGGG, OEGGG and the DGGG/OEGGG/SGGG guidelines commission in September 2022 and was thus approved in its entirety. This guideline is valid for 5 years – from September 2022 through to September 2027. Because of the contents of this guideline, this period of validity is only an estimate. The guideline can be reviewed and updated at an earlier point in time if urgently required. Likewise, the guidelineʼs period of validity can be extended if the guideline still reflects the current state of knowledge.


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#

III  Methodology

Basic principles

The method used to prepare this guideline was determined by the class to which this guideline was assigned. The AWMF Guidance Manual (version 1.0) has set out the respective rules and requirements for different classes of guidelines. Guidelines are differentiated into lowest (S1), intermediate (S2), and highest (S3) class. The lowest class is defined as consisting of a set of recommendations for action compiled by a non-representative group of experts. In 2004, the S2 class was divided into two subclasses: a systematic evidence-based subclass (S2e) and a structural consensus-based subclass (S2k). The highest S3 class combines both approaches.

This guideline was classified as: S3.


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Assessment of evidence using the Oxford CEBM system

To evaluate the evidence (levels 1 – 5), this guideline used the most recent 2011 version of the Oxford Centre for Evidence-based Medicine classification system ([Table 3]).

Table 3 Levels of Evidence according to Oxford Centre for Evidence-Based Medicine 2011.

Question

Level 1*

Level 2*

Level 3*

Level 4*

Level 5

*  Level may be downgraded because of study quality, extended confidence intervals (imprecise effect estimates), inconsistencies between studies, or because the absolute effect value is very small, as well as lack of transferability (study question does not correspond to the clinically relevant question). An upgrade of the evidence level is possible in case of large or very large effects.

**  As a general rule, a systematic review is always better than a single study.

***  Consecutive inclusion = patients are continuously recruited.

1  The STROBE statement, among others, can be used for quality assessment: http://www.strobe-statement.org/index.php?id=strobe-aims.

2  Single-patient studies in which patients receive alternating intervention and control intervention.

3  Follow-up study of a population from a completed RCT.

4  Study in which cases and controls are drawn from an ongoing cohort study.

How widespread is the problem?

Local and current random sample or census (complete survey)

Systematic review of surveys that can be applied to local circumstances**

Local survey that is not based on a random sample**

Case series**

Not applicable

Is this diagnostic or controlling test accurate? (Diagnostic)

Systematic review of cross-sectional studies with reference standard applied throughout and blinding

Single cross-sectional study with reference standard applied throughout and blinding

Non-consecutive*** study or study without applied reference standard**

Case-control study or study with inappropriate or non-independent reference standard**

Expert opinion based on pathophysiological considerations

What would happen if we did not apply therapy? (prognosis)

Expert opinion based on pathophysiological considerations

Single cohort study of patients in the early stages of the disease (inception cohort study)

Cohort study or control arm of a randomized trial*

Case series or case-control study or a prognostic cohort study with low methodological quality1**

Not applicable

Does this approach help? (use of the intervention)

Systematic review of randomized trials or N-of-1 studies2

Randomized trial or observational study with dramatic effects

Controlled cohort study/follow-up study3**

Case series or case-control studies or studies with historical controls**

Expert opinion based on pathophysiological considerations

What are common side effects? (harm of intervention)

Systematic review of either randomized trials or embedded case-control studies4. Or N-of-1 study with patients matching the research question or observational study with dramatic effects

Randomized trial or (exceptionally) observational study with dramatic effects

Controlled cohort study/follow-up (post-marketing surveillance) study, with sufficient number of cases to identify a common side effect. If long-term side effects are to be recorded, the follow-up must be sufficient**.

What are rare side effects? (harm of the intervention)

Systematic review of randomized trials or N-of-1 studies

Randomized trial or (exceptionally) observational study with dramatic effects

Is this screening test useful? (screening)

Systematic review of randomized studies

Randomized trial


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Grading of recommendations

The grading of evidence in an S3-guideline using a level-of-evidence system allows the strength of the recommendations made in the guideline to be graded. The degree of recommendation is differentiated into three levels, and the different strengths of recommendation are indicated by the respective choice of words. This commonly used grading of recommendations is not just used by the AWMF but also by the German Medical Association in its National Guidelines on Care (Nationale Versorgungsleitlinien, NVL). The wording chosen to indicate the strength of the recommendation should be explained in the background text.

In this context, the terms “grade,” “level” or “strength” indicate the degree of certainty about issuing the recommendation after weighing up the benefits and the harms; they are not an indication of whether the recommendation itself is binding. Guidelines are recommendatory in nature, i.e., they cannot be binding. Individual statements and recommendations are differentiated by symbols and syntax ([Table 4]).

Table 4 Grading of recommendations. English translation of the long version of the guideline.

Recommendation grade

Description

Expression

A

Strong recommendation

shall

B

Recommendation

should

0

Recommendation open

can

The above-described classification of “recommendations” reflects both the assessment of the evidence and the clinical relevance of the studies on which the evidence is based as well as factors which were not included in the grading of evidence, such as the choice of patient cohort, intention-to-treat and outcome analyses, medical actions and ethical behavior towards the patient, country-specific applicability, etc. In contrast, high, moderate, or low levels of evidence may result in a strong, simple, or open recommendation. A recommendation can only be upgraded or downgraded to a grade A or a grade 0 recommendation if the level of evidence is moderate. In exceptional cases, the highest level of evidence is only accorded a limited/open recommendation or vice versa, and this must be explained in the background text. The downgrading of a high level of evidence to a weaker/open recommendation in exceptional cases or the reverse must be justified in the background text.

  • Strong level of evidence → grade A or grade B recommendation

  • Moderate level of evidence → grade A or grade B or grade 0 recommendation

  • Weak level of evidence → grade B or grade 0 recommendation


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Statements

Expositions or explanations of facts, circumstances, or problems with no direct recommendations for action in this guideline are referred to as “statements.” It is not possible to provide any information about the grading of evidence for these statements.


#

Achieving consensus and strength of consensus

At structured NIH-type consensus-based conferences (S2k/S3 level), authorized participants attending the session vote on draft statements and recommendations. The process is as follows. A recommendation is presented, its contents are discussed, proposed changes are put forward, and all proposed changes are voted on. If a consensus (> 75% of votes) is not achieved, there is another round of discussions, followed by a repeat vote. Finally, the extent of consensus is determined, based on the number of participants ([Table 5]).

Table 5 Level of consensus based on extent of agreement.

Level of consensus

Extent of agreement in percent

Strong consensus

> 95% of voters agree

Consensus

> 75 – 95% of voters agree

Majority consensus

> 50 – 75% of voters agree

Dissent

< 50% of voters agree


#

Expert consensus

As the term already implies, this refers to consensus decisions taken specifically with regards to recommendations/statements issued without a prior systematic search of the literature (S2k) or where evidence is lacking (S2e/S3). The term “expert consensus” (EC) used here is synonymous with terms used in other guidelines such as “good clinical practice” (GCP) or “clinical consensus point” (CCP). The strength of the recommendation is graded as previously described in the chapter Grading of recommendations but without the use of symbols; it is only expressed semantically (shall/should/can).


#
#

IV  Guideline

1  Treatment of precancerous endometrial lesions and early-stage endometrial cancer

1.1  Endometrial hyperplasias

No.

Recommendations/Statements

GoR

LoE

Sources

5.1

Simple endometrial hyperplasia without atypia should not be treated by hysterectomy.

B

3

[1], [2]

5.2

Hysterectomy may be considered for complex endometrial hyperplasia without atypia.

0

3

[1]

5.3

In postmenopausal patients and in premenopausal patients with completed family planning and presence of atypical hyperplasia of the endometrium, total hysterectomy with bilateral salpingectomy and, if necessary, bilateral ovariectomy shall be performed.

A

1

[2], [3]

5.4

In the presence of atypical hyperplasia, the ovaries may be left in place when performing hysterectomy and bilateral salpingectomy in premenopausal women, provided there is no evidence of a hereditary predisposition to ovarian cancer (e.g., BRCA mutation or certain forms of Lynch syndrome).

EC

5.5

If uterus preservation is desired, the uterus and adnexa may be left in place in the presence of atypical hyperplasia if the patient has been informed that the standard treatment almost always leading to cure is total hysterectomy, agrees to close monitoring and has been informed of the need for hysterectomy after the desire for a child has been fulfilled or abandoned.

EC

5.6

If uterus preservation is desired, the uterus and adnexa may be left in place in the presence of atypical hyperplasia if a hysteroscopy with targeted biopsy or with curettage was performed to confirm the diagnosis and the diagnosis “atypical hyperplasia” was made or confirmed by a pathologist experienced in gynecologic pathology.

EC

5.7

If uterus preservation is desired, the uterus and adnexa may be left in place in the presence of atypical hyperplasia if laparoscopy with vaginal ultrasound or MRI has been performed to best assess the risk of adnexal involvement and/or myometrial infiltration.

EC

5.8

If complete remission of AEH is seen after 6 months of conservative treatment, planned pregnancy should be pursued.

EC

5.9

If there is currently no desire to have a child, maintenance therapy shall be performed. An endometrial biopsy should be performed every 6 months.

EC

5.10

After fulfillment or abandonment of the desire to have children, a total hysterectomy (+/− bilateral salpingectomy +/−, bilateral ovariectomy) shall be performed.

A

4

[4], [5], [6], [7], [8]


#

1.2  Early-stage endometrial cancer

No.

Recommendations/Statements

GoR

LoE

Sources

5.11

In the presence of early endometrial carcinoma (endometrioid, pT1a G1), total hysterectomy with bilateral adnexal extirpation results in a disease-specific 5-year survival of 99%.

A

3

[9]

5.12

In the presence of endometrioid endometrial carcinoma G1, G2 pT1a, the ovaries may be left in place when performing hysterectomy and bilateral salpingectomy in premenopausal women, provided there is no evidence of hereditary predisposition to ovarian cancer (e.g., BRCA mutation, certain forms of Lynch syndrome) and the patient is informed of the risk.

EC

5.13

In women with incomplete family planning and endometrioid cT1a without myometrial infiltration, G1, p53-wt and L1CAM-negative endometrial carcinoma and a desire for fertility preservation, the uterus and adnexa can be left in place if the patient has been informed that the standard treatment almost always leading to cure is total hysterectomy and that the patient temporarily forgoes curative treatment of a malignancy on her own responsibility, knowing the potentially fatal consequences (progression of the disease, metastasis) even if a pregnancy is carried to term.

EC

5.14

If uterus preservation is desired, the uterus and adnexa can be preserved in the presence of endometrioid cT1a, without myometrial infiltration G1, p53-wt, and L1CAM-negative endometrial carcinoma if the patient has been recommended a consultation with a specialist in reproductive medicine to assess the chances of fulfilling a childbearing desire.

EC

5.15

If uterus preservation in endometrioid cT1a, without myometrial infiltration G1, p53-wt and L1CAM-negative endometrial carcinoma are desired, the uterus and adnexa can be left in place if the patient agrees to close monitoring and has been informed of the need for hysterectomy after fulfillment or abandonment of the desire to have children.

EC

5.16

In endometrioid cT1a without myometrial infiltration, G1, p53-wt and L1CAM- negative endometrial carcinoma and desire for fertility preservation, the uterus and adnexa can be left in place if a diagnosis of well-differentiated (G1) endometrioid EC expressing progesterone receptors has been made by hysteroscopy with targeted biopsy or with dilatation and curettage and evaluation by a pathologist experienced in gynecologic pathology.

EC

5.17

In endometrioid cT1a without myometrial infiltration, G1, p53-wt, and L1CAM-negative endometrial cancer and desire for fertility preservation, the uterus and adnexa can be left in place if laparoscopy with vaginal ultrasound or if MRI has ruled out adnexal involvement or myometrial infiltration as much as possible.

EC

5.18

In endometrioid cT1a without myometrial infiltration, G1, p53-wt, and L1CAM-negative endometrial cancer and desire for fertility preservation, the uterus and adnexa can be left in place if sufficient drug treatment is given with medroxyprogesterone acetate 200 – 250 mg/d/p. o.) or megestrol acetate (160 – 200 mg/d/p. o.) or a levonorgestrel IUD (52 mg).

EC

5.19

If a complete remission of the endometrial carcinoma is diagnosed after six months of conservative treatment, the planned pregnancy should be pursued in cooperation with a specialist in reproductive medicine if necessary.

EC

5.20

Patients with endometrioid cT1a without myometrial infiltration, G1, p53-wt, and L1CAM-negative endometrial cancer without a current desire to have children should receive maintenance therapy (levonorgestrel-IUD, oral contraceptives, cyclic progestins) and have an endometrial biopsy every 6 months.

EC

5.21

If there is no remission of the carcinoma after six months of conservative treatment, hysterectomy should be performed.

EC

5.22

If uterus preservation is desired, the uterus and adnexa can be left in the presence of endometrioid endometrial cancer (cT1a, G1, p53-wt, and L1CAM-negative) if the following conditions are met:

  • Information that the standard treatment almost always leading to cure is total hysterectomy,

  • Consent with close follow-up,

  • Information about the necessity of hysterectomy after fulfillment or abandonment of the desire to have a child,

  • Hysteroscopy with targeted biopsy or dilatation and curettage to confirm diagnosis,

  • Laparoscopy with vaginal ultrasound or MRI to rule out adnexal involvement/myometrial infiltration,

  • Diagnosis made or confirmed by a pathologist experienced in gynecologic pathology,

  • Treatment with MPA or MGA or LNG-IUD (52 mg),

  • After 6 months, repeat hysteroscopy withdilatation and curettage as well as imaging. If no remission, hysterectomy,

  • If complete remission, aim for pregnancy (expert in reproductive medicine),

  • If no current desire to have children: maintenance therapy and endometrial biopsy every 6 months,

  • after fulfillment or abandonment of the desire to have children: total hysterectomy and bilateral adnexal extirpation recommended.

EC


#
#

2  Surgical treatment of endometrial cancer

2.1  Basic principles of surgical treatment

No.

Recommendations/Statements

GoR

LoE

Sources

6.1

In endometrial carcinoma cT2 or pT2 (with histologic evidence of involvement of the cervical stroma) without clinical suspicion of parametrial infiltration, radical hysterectomy (parametrial resection) shall not be performed.

A

3

[10]


#

2.2  Lymphadenectomy

No.

Recommendations/Statements

GoR

LoE

Sources

6.2

In patients with endometrial carcinoma (all stages and histologies), the lymph nodes that appear enlarged on laparoscopic or open inspection of the abdominal cavity and/or are susspicuous on palpation (“bulky nodes”) shall be removed.

EC

6.3

Lymph node sampling of inconspicuous lymph nodes shall not be performed.

EC

6.4

When surgical lymph node staging is performed in patients with endometrial cancer, it shall be performed as a systematic LNE or sentinel node biopsy rather than sampling.

EC

6.5

In low-risk type I endometrial carcinoma pT1a, G1/2, no bulky nodes, systematic lymphadenectomy shall not be performed.

A

1

[11]

6.6

If pT1a (without myometrial infiltration), G1/G2, a p53 mutation (intermediate risk), or L1CAM overexpression (high-intermediate risk) is present in a type I endometrial carcinoma, a sentinel node biopsy can be performed, followed by systematic LNE if necessary.

EC

6.7

If a type I endometrial carcinoma cT1a, G3, or cT1b, G1/2 and no p53 mutation (i.e., at least an intermediate risk endometrial carcinoma) is present preoperatively, sentinel node biopsy can be performed, followed by systematic LNE if necessary.

Primary systematic LNE should be omitted.

EC

6.8

In endometrial cancer type I, cT1b, G3 (high-intermediate risk group), surgical lymph node staging – sentinel LNE or (sentinel-assisted) systematic LNE – should be performed.

EC

6.9

If type I endometrial carcinoma cT1a, G3, or cT1b, G1/2 and a p53 mutation (high risk) are present preoperatively, surgical lymph node staging – sentinel LNE and/or (sentinel-assisted) systematic LNE – should be performed.

EC

6.10

If extensive lymphatic vessel invasion (at least high-intermediate risk group) is present in endometrial carcinoma type I stage I, pT1a G1-G3, pT1b G1/G2, a systematic LNE should be performed, even if no other risk factors are present. If a negative sentinel is present, LNE can be omitted.

EC

6.11

In endometrial carcinoma type I, pT2 to pT4, M0, G1-3, (sentinel-assisted) systematic lymphadenectomy should be performed if macroscopic tumor resection can be achieved.

EC

6.12

If bulky nodes are present in patients with endometrial cancer (all stages, all histologies), sentinel node biopsy is no longer informative.

ST

4

[12]

6.13

In endometrial carcinoma type II, (sentinel-assisted) systematic lymphadenectomy should be performed if complete tumor resection can be achieved macroscopically.

EC

6.14

If systematic LNE is indicated, it should be performed pelvic and infrarenal-para-aortic.

B

3

[13], [14], [15], [16], [17], [18]

6.15

For carcinosarcomas of the uterus, (sentinel-assisted) systematic LNE should be performed.

EC

6.16

The combination of systematic LNE and sentinel biopsy (that is, sentinel-assisted LNE) may improve the detection of positive lymph nodes.

EC

6.17

If sentinel node biopsy is performed, it should be done according to the following algorithm:

  • Laparoscopy and visualization of the situs (adhesiolysis if necessary)

  • Intracervical injection of ICG

  • A re-injection of ICG, if necessary

  • If only unilateral visualization of a sentinel is possible despite re-injection of ICG, a systematic pelvic LNE should be performed on the ICG-negative side (except in pT1a/G1-2)

  • Work-up of the sentinel lymph node by ultrastaging (details see background text)

EC


#

2.3  Laparoscopic surgery

No.

Recommendations/Statements

GoR

LoE

Sources

6.18

For endometrioid adenocarcinoma of the endometrium at a presumed early stage, hysterectomy and bilateral adnexal extirpation should be performed by a laparoscopic or laparoscopically assisted vaginal procedure.

B

1

[19], [20], [21]


#

2.4  Robot-assisted surgery

No.

Recommendations/Statements

GoR

LoE

Sources

6.19

Robot-assisted laparoscopic procedures can be used in the same manner as conventional laparoscopy for endometrial cancer surgery. They may offer advantages in morbidly obese patients.

0

3

[22], [23], [24]


#

2.5  Tumor reduction in advanced endometrial cancer

No.

Recommendations/Statements

GoR

LoE

Sources

6.20

In advanced endometrial cancer (including carcinosarcoma), surgical tumor reduction can be performed with the goal of macroscopic complete tumor resection.

0

4

[25], [26], [27]

6.21

For advanced endometrial cancer that cannot be primarily resected, neoadjuvant platinum-containing chemotherapy followed by cytoreductive surgery may be considered.

0

4

[25]


#
#

3  Radiotherapy for endometrial cancer

3.1  Postoperative adjuvant radiotherapy for type I, stage I – II endometrial cancer

No.

Recommendations/Statements

GoR

LoE

Sources

7.1

In all stage I and II endometrial carcinomas with POLE mutation, adjuvant radiotherapy and/or chemotherapy can be omitted in R0 situation, even if risk factors are present.

0

3

[28]

7.2

In stage pT1a, pNX/0, G1 or G2, endometrioid endometrial carcinoma (type I), p53-wt and L1CAM negative, no extensive LVSI after hysterectomy with or without lymph node dissection, neither brachytherapy nor percutaneous irradiation should be performed.

EC

7.3

In stage pT1a, pNX/0 without involvement of the myometrium, G3, endometrioid endometrial cancer (type I), vaginal brachytherapy can be performed to reduce the risk of vaginal recurrence.

0

4

[29], [30]

7.4

In stage pT1a, pNX/0 without involvement of the myometrium, G1-3, p53-abn or L1CAM positive (each POLE wild type), endometrioid endometrial carcinoma (type I), adjuvant vaginal brachytherapy or percutaneous radiotherapy can be performed, if necessary in combination with chemotherapy.

EC

7.5

In stage pT1b, G1 or G2 pNX/0 and in stage pT1a (with myometrial involvement), G3 pNX/0, endometrioid endometrial carcinoma (type I), p53-wt, L1CAM negative, no extensive LVSI, postoperative vaginal brachytherapy alone shall be performed.

A

2

[31], [32], [33], [34], [35], [36]

7.6

In stage pT1b, G1-3 pNX/0 and in stage pT1a (with myometrial involvement), G1-3 pNX/0, endometrioid endometrial carcinoma (type I), p53- abn and/or L1CAM positive and/or extensive LVSI, percutaneous irradiation shall be performed postoperatively.

A

3

[32], [33], [37], [38], [39], [40], [41], [42], [43]

7.7

Radiation should be given in combination with chemotherapy in this situation (7.6.). See the Chapter on adjuvant medical therapy.

EC

7.8

In patients with endometrioid endometrial carcinoma (type I) stage pT1b pN0 G3 (without LVSI and p53-wt and L1CAM negative) vaginal brachytherapy shall be performed.

A

3

[32], [33], [44], [45]

7.9

Patients with stage pT2 pNX with additional risk factors (G3 or > 50% myometrial infiltration or LVSI) shall receive percutaneous radiotherapy.

A

3

[32], [33], [44], [45]

7.10

For patients with stage pT1b pNX G3 (without LVSI, p53-wt, L1CAM negative), endometrioid endometrial cancer (type I), vaginal brachytherapy or percutaneous radiotherapy shall be performed.

A

3

[32], [33], [44], [45]

7.11

Patients with stage pT2 pNx, G1/G2, (less than 50% myometrial infiltration, without LVSI, p53-wt, L1CAM negative), endometrioid endometrial carcinoma (type I), shall receive vaginal brachytherapy or percutaneous radiotherapy.

A

3

[32], [33], [44], [45]

7.12

Patients with endometrioid endometrial carcinoma (type 1) stage pT1b and pT2 p53-abn, POLE-wt shall receive percutaneous radiotherapy in combination with chemotherapy (PORTEC 3 regimen).

A

3

[32], [33], [39], [44], [45]

7.13

For patients with stage pT2 pNX G3 or > 50% myometrial infiltration or LVSI, radiation can be given in combination with chemotherapy.

EC

7.14

In patients with stage pT2 pN0 endometrioid endometrial carcinoma (type I) (without other risk factors such as G3, > 50% myometrial infiltration or LVSI and p53-wt AND L1CAM negative), endometrioid endometrial carcinoma (type I), vaginal brachytherapy shall be performed.

A

3

[32], [33], [44], [45]

7.15

Patients with endometrioid endometrial carcinoma (type I) pT2 pN0 with risk factors (> 50% myometrial infiltration or LVSI or L1CAM positive) should receive percutaneous pelvic radiotherapy.

B

3

[32], [33], [44], [45]


#

3.2  Postoperative radiotherapy for type I, stage III–IVA endometrial cancer

No.

Recommendations/Statements

GoR

LoE

Sources

7.16

Patients with endometrioid endometrial carcinoma (type I) and positive lymph nodes, involvement of the uterine serosa, adnexa, vagina, bladder, or rectum (stages III-IVA) should receive adjuvant percutaneous radiotherapy followed by simultaneous chemotherapy or, alternatively, chemotherapy alone in combination with vaginal brachytherapy.

B

3,5

[40], [46]

7.17

Patients with endometrioid EC (type I) and positive lymph nodes, involvement of the uterine serosa, adnexa, vagina, bladder, or rectum (stages III–IVA) can alternatively receive adjuvant chemotherapy followed by percutaneous radiotherapy.

EC

7.18

If simultaneous radiochemotherapy followed by chemotherapy is chosen, the regimen used in the PORTEC-3 trial should be applied.

EC

7.19

When chemotherapy is combined with vaginal brachytherapy alone, brachytherapy can be given after or between chemotherapy administrations.

EC


#

3.3  Vaginal brachytherapy as a boost after postoperative percutaneous pelvic radiation

No.

Recommendations/Statements

GoR

LoE

Sources

7.20

In the presence of specific risk factors for vaginal recurrence (stage II or stage IIIB-vaginal or LSVI or close vaginal resection margin, additional vaginal brachytherapy can be performed as a boost after postoperative pelvic irradiation after hysterectomy due to endometrioid endometrial carcinoma.

EC


#

3.4  Postoperative radiotherapy for type II endometrial cancer

No.

Recommendations/Statements

GoR

LoE

Sources

7.21

Patients with serous endometrial carcinoma and patients with p53-mutated endometrial carcinoma of all stages should receive vaginal brachytherapy (stage I) or adjuvant percutaneous radiotherapy (stage II and above).

EC


#

3.5  Primary radiotherapy alone for inoperable disease


#

3.6  Radiotherapy for carcinosarcoma ([Table 6])

Table 6 Suggestions for radiotherapy to treat uterine carcinosarcomas based on staging of the lesion.

Stage

Only external radiotherapy

Only vaginal brachytherapy

Combination (external + brachytherapy)

IA

(+)

+

(+)

IB

+

+

+

II

(+)

(+)

+

III

(+)

(+)

+

IV

(+)

0

No.

Recommendations/Statements

GoR

LoE

Sources

7.22

To improve local control, postoperative radiotherapy should be given in addition to chemotherapy for carcinosarcoma when stage FIGO I or II is present.

B

3

[47]

7.23

In the case of carcinosarcoma, an individualized radiation concept can be implemented if higher stages are present.

EC


#

3.7  Supportive therapy

The recommendations of the German-language S3-guideline on supportive therapy for oncological patients (https://www.leitlinienprogramm-onkologie.de/leitlinien/supportive-therapie/) must be considered when administering radiotherapeutic treatment. See recommendation 9.9 in chapter 5.

Supportive therapy is an integral part of the treatment concept. Side effects may occur and take the form of acute changes occurring during or directly following treatment or as late sequelae of treatment.


#
#

4  Adjuvant medical therapy for endometrial cancer

4.1  Adjuvant medical therapy for endometrial cancer

No.

Recommendations/Statements

GoR

LoE

Sources

8.1

Adjuvant progestin therapy after surgery for endometrial cancer shall not be performed.

A

1

[48]

8.2

Patients with primary type I endometrial carcinoma stage pT1a/b G1 and G2 cN0/ pNsn0, p53-wt, shall not receive adjuvant chemotherapy.

EC

8.3

For patients with endometrioid or other type I endometrial carcinoma at stage pT1a G3 cN0 or pN0, p53-wt, there are insufficient data on the benefit of adjuvant chemotherapy.

ST

2

[49]

8.4

For patients with type I endometrial carcinoma G3 pT1b, without POLE mutation or stage pT2 (each pN0), adjuvant chemotherapy with 3 or 6 cycles (see Statement 8.13) may be considered as an adjunct to vaginal brachytherapy (see Radiation Therapy recommendation) or percutaneous radiotherapy alone without chemotherapy.

0

2

[49], [50]

8.5

Patients with type I endometrial carcinoma G3 pT1b or stage pT2 (both pN0) with POLE mutation should not receive adjuvant chemotherapy.

EC

8.6

Patients with serous endometrial carcinoma in FIGO stage I–III should receive adjuvant therapy according to the PORTEC-III regimen (= radiochemotherapy followed by chemotherapy). For stage III serous endometrial carcinoma, adjuvant chemotherapy alone can be given as an alternative (carboplatin AUC 6/paclitaxel 175 mg/m2).

B

2

[46], [51]

8.7

Patients with type 1 endometrial carcinoma and abnormal p53 status on immunohistochemistry (type I endometrial carcinoma stage 1a or higher, with infiltration into the myometrium, or clear cell endometrial carcinoma) should be treated like patients with serous endometrial carcinoma.

EC

8.8

Patients with primary endometrial cancer stage pT3 and/or pN1 shall receive adjuvant chemotherapy or adjuvant therapy according to the PORTEC-3 regimen.

A

2

[38], [39], [40], [46]

8.9

Patients with stage pT4a or M1 endometrial cancer who have undergone macroscopic complete tumor resection or have a maximum postoperative residual tumor less than 2 cm should receive adjuvant chemotherapy, if applicable in combination with radiotherapy.

B

1

[46], [49], [50]

8.10

Adjuvant chemotherapy for endometrial cancer shall be given with carboplatin AUC 6 and paclitaxel 175 mg per square meter. After percutaneous radiotherapy, carboplatin AUC 5 should be dosed.

A

2

[46], [52], [53]

8.11

If chemotherapy alone is indicated and paclitaxel or carboplatin are contraindicated, adriamycin and cisplatin may also be used.

A

2

[46], [52], [53]

8.12

Patients with carcinosarcoma FIGO stage I or II may receive adjuvant chemotherapy with carboplatin/paclitaxel (at a dosage of paclitaxel 175 mg/m2 day 1 carboplatin AUC 6 day 1) or cisplatin/ifosfamide (at a dosage of ifosfamide 1.6 g/m2 day 1–4 and cisplatin 20 mg/m2 day 1–4).

0

4

[54]

8.13

For patients with stage FIGO III or IV carcinosarcoma, adjuvant chemotherapy with ifosfamide/paclitaxel or ifosfamide/cisplatin was shown to have a significant survival benefit over monotherapy with ifosfamide.

ST

1

[55], [56], [57]

8.14

Given the high toxicity of ifosfamide-containing combinations, the combination of carboplatin and paclitaxel can also be used as adjuvant chemotherapy in patients with stage FIGO III or IV carcinosarcoma at a dosage of paclitaxel 175 mg/m2 day 1 and carboplatin AUC 6 or cisplatin/ifosfamide at a dosage of ifosfamide 1.6 g/m2 i.v. day 1–4 and cisplatin 20 mg/m2 i.v. day 1–4.

EC


#
#

5  Follow-up/recurrence/metastasis of endometrial cancer

5.1  Follow-up

No.

Recommendations/Statements

GoR

LoE

Sources

9.1

There is no evidence that follow-up examinations of women with endometrial cancer result in prolonged survival.

ST

4

[58], [59], [60], [61], [62], [63], [64], [65], [66], [67]

9.2

A medical history with specific query of symptoms and clinical gynecological examination with speculum and rectovaginal palpation examination should be performed at 3- to 6-month intervals for the first 3 years after completion of primary therapy and semi-annually in years four and five.

EC

9.3

Imaging studies and tumor marker determinations should not be performed in asymptomatic patients.

B

4

[58], [59], [60], [65]


#

5.2  Locoregional recurrence

No.

Recommendations/Statements

GoR

LoE

Sources

9.4

If local recurrence in the vagina or pelvis is suspected or if distant metastases are suspected, histological confirmation shall be sought.

EC

9.5

Cross-sectional imaging shall be performed if vaginal recurrence, pelvic recurrence or distant metastasis is suspected or after histologic confirmation of vaginal recurrence, pelvic recurrence or distant metastasis.

A

3

[58], [68], [69]

9.6

Women with isolated vaginal or vaginal stump recurrence after endometrial cancer without prior radiation therapy as part of primary treatment should receive radiation therapy with curative intent, consisting of external pelvic radiation and brachytherapy with or without local tumor resection.

EC

9.7

Women with isolated vaginal or vaginal stump recurrence after endometrial cancer with adjuvant brachytherapy alone as part of primary treatment, radiotherapy with or without local tumor resection may be given with curative intent.

EC

9.8

Women with vaginal or vaginal stump recurrence in status post external pelvic irradiation with or without brachytherapy, should be evaluated to determine whether new radiotherapy as external irradiation or brachytherapy with or without local tumor resection in curative intention is possible.

EC

9.9

Local late effects of radiotherapy shall be treated according to the S3 Guideline “Supportive therapy in oncology patients” [87].

EC


#

5.3  Surgical treatment for recurrence

No.

Recommendations/Statements

GoR

LoE

Sources

9.10

Provided that complete resection of the recurrent tumor appears achievable and cross-sectional imaging has shown no evidence of distant metastasis, surgical therapy for endometrial cancer recurrence can be performed.

EC

9.11

Exenteration has not been shown to improve duration of survival, survival rate or progression-free survival in women with recurrence after endometrial cancer compared with other therapies or best supportive care.

EC

9.12

Exenteration may be considered in individual cases in women with recurrence after endometrial cancer.

EC


#

5.4  Endocrine therapy for recurrence

No.

Recommendations/Statements

GoR

LoE

Sources

9.13

There is no evidence that endocrine therapy improves duration of survival or survival rate or progression-free survival in women with recurrence after endometrial cancer compared with other therapies or best supportive care.

EC

9.14

Endocrine therapy with MPA (200–250 mg/d) or MGA (160 mg/d) or tamoxifen (20 mg/d or 40 mg/d) or a combination of tamoxifen and MPA/MGA can be given to women with recurrence after endometrial cancer.

0

3

[70], [71], [72], [73], [74]

9.15

In women with recurrence after endometrial cancer, endocrine therapy with MPA or tamoxifen results in higher response rates when progesterone receptor expression or estrogen receptor expression or well to-moderate tumor differentiation (G1/G2) is detectable.

ST

3

[70], [72], [73], [75]


#

5.5  Chemotherapy for recurrence

No.

Recommendations/Statements

GoR

LoE

Sources

9.16

Chemotherapy can be given to women with locally non-treatable endometrial cancer recurrence or distant metastasis.

0

1

[58], [76]

9.17

The superiority of a particular chemotherapy regimen in women with recurrence after endometrial carcinoma has not been established. The carboplatin/paclitaxel and doxorubicin/cisplatin/paclitaxel combinations have been shown to be equally effective agents for chemotherapeutic therapy of advanced or recurrent endometrial carcinoma. Because of better tolerability, carboplatin (AUC 6) shall be used with paclitaxel (175 mg/m2).

A

2

[53], [76]


#

5.6  Immunotherapy for recurrence of endometrial cancer

No.

Recommendations/Statements

GoR

LoE

Sources

9.18

In patients with locally advanced or recurrent serous endometrial cancer with HER2/neu overexpression, systemic chemotherapy with carboplatin (AUC 5) and paclitaxel (175 mg/m2) combined with trastuzumab (8 mg/kg as initial dose, followed by 6 mg/kg as maintenance therapy) can be given.

0

2

[77]

9.19

Patients with recurrent or primary advanced endometrial cancer with microsatellite-stable/mismatch-repair functional tumor tissue and progression after at least one line of chemotherapy should receive combined immune and multikinase inhibitor therapy with pembrolizumab (200 mg i.v. d1, q21 or 400 mg i.v. d1, q42) and lenvatinib (20 mg p.o. 1 × daily). The high toxicity should be noted.

B

2

[78], [79]

9.20

In patients with recurrent or primary advanced endometrial cancer with microsatellite unstable/mismatch repair deficient tumor tissue (MSI-H or dMMR), immunotherapy with dostarlimab (4 cycles 500 mg i.v. d1, q3w followed by 1000 mg i.v. d1, q6w) or with pembrolizumab (200 mg i.v. d1, q21 or 400 mg i.v. d1, q42) can be performed after preceding platinum-based therapy.

0

3

[80], [81], [82], [83]


#

5.7  Actinic changes in the irradiated area

No.

Recommendations/Statements

GoR

LoE

Sources

9.21

Symptoms of vaginal atrophy in patients after therapy for endometrial cancer shall be treated primarily with inert lubricating gels or creams.

A

3

[84]

9.22

Local estrogen treatment after primary therapy for endometrial cancer may be considered, after unsatisfactory treatment with inert lubricating gels or creams.

EC

9.23

Vaginal dilators can be used for the treatment and prophylaxis of vaginal stenosis in patients with endometrial cancer after the end of radiotherapy and resolution of acute radiation sequelae.

EC


#

5.8  Palliative radiotherapy

No.

Recommendations/Statements

GoR

LoE

Sources

9.24

As a palliative measure for vaginal bleeding or pain from vaginal stump or pelvic wall recurrence, low total dose radiotherapy can be used even after previous radiotherapy.

EC


#
#

6  Psycho-oncological aspects, patient education, palliative care, rehabilitation, physiotherapy as part of rehabilitation

6.1  Psycho-oncological aspects ([Table 7])

Table 7 Recommendations from the S3-guideline “Psycho-oncological Diagnosis, Counseling and Treatment of Adult Cancer Patients,” Version 1.1, updated June 2021.

No.

Text of recommendation

11.3

Psychosocial problems and the individual level of need for psycho-oncological support should be recorded as early as possible and should be repeatedly reviewed over the course of disease.

11.4

All patients must be screened for psychosocial problems. Psycho-oncological screening should be carried out as early as possible and repeated at reasonable intervals over the course of disease, when clinically indicated, or if there are changes in the patientʼs disease status (e.g., recurrence or progression of disease); screening should also be carried out in long-term survivors.

11.5

Validated and standardized screening tools must be used to record psychosocial problems. The screening tools which must be used include the Distress Thermometer (DT), the Hospital Anxiety and Depression Scale (HADS), the questionnaire on the stress of cancer patients (FBK), the Depression module of the Patient Health Questionnaire (PHQ-9) or the Generalized Anxiety Disorder Scale-7 (GAD-7) (LoE 1b).

11.6

In addition to screening to identify problems, the patient must be asked about her subjective psychosocial need for support (EC).

11.7

A diagnostic discussion to evaluate psychosocial problems and psychological comorbidities must follow if screening results are positive and/or at the patientʼs request.

11.8

Further diagnostic evaluation should follow, based on the individual psychological/social/somatic problems identified in the discussion.

No.

Recommendations/Statements

GoR

LoE

Sources

11.1

Patients with endometrial cancer and their families may face multiple physical, psychological, social and spiritual/religious stresses.

EC

11.2

Cancer patients and their relatives shall be informed about psychosocial support, counseling and treatment services as early as possible in all phases of the disease and shall be given access to these services according to their individual needs.

EC

11.3

The indication for psycho-oncological interventions shall be made according to the identified individual need, the setting, and the patientʼs disease phase (initial diagnosis, surgery, adjuvant therapy, recurrence-free phase, relapse phase, palliative phase, long-term survival) and should take into account the patientʼs wishes.

EC

11.4

The topic of sexuality shall be actively addressed in the various phases of the treatment process and follow-up care for patients with endometrial cancer, in order to assess the need for support and to be able to initiate appropriate assistance.

EC


#

6.2  Patient education and information

No.

Recommendations/Statements

GoR

LoE

Sources

11.5

Qualified and relevant information materials (print or internet media, e.g. the patient guideline on uterine cancer), which have been prepared according to defined quality criteria for health information, shall be made available to patients in order to support them in their self-determined decision for or against medical measures through generally understandable risk communication (e.g. indication of absolute risk reductions).

EC

11.6

The patient shall be offered to include her partner or relatives/trustworthy persons in the conversation(s) for the purpose of communicating the diagnosis and in further conversations during therapy and for follow-up care.

EC

11.7

During the medical consultation, the patientʼs individual preferences, needs, concerns and fears shall be determined and taken into account. If a patient requires more than one consultation, the offer of further consultations should be made.

EC

11.8

The communication of information and education of the patient shall take place at an early stage and according to the basic principles of patient-centered communication, which enables participatory decision-making. This should include the following aspects:

  • Expression of empathy and active listening,

  • Addressing difficult issues directly and empathetically,

  • Avoidance of technical medical vocabulary, explanation of technical terms when appropriate,

  • Strategies to improve understanding (repetition, summarizing important information, use of graphics, etc.),

  • Encouragement to ask questions,

  • Permission and encouragement to express feelings,

  • Offering further help.

EC

11.9

To improve patient education, physicians should complete quality-assured training on communication with patients.

EC

11.10

The patient shall be made aware of self-help options and given contact information for self-help organizations.

EC

11.11

Patients with endometrial cancer shall be informed about the treatment options described in this Guideline that are relevant for them, their prospects of success and their possible effects. In particular, the impact on their physical appearance, sexual life, urinary and fecal control (incontinence) and aspects of female self-image (self-image, fertility, menopausal symptoms) shall be addressed.

EC


#

6.3  Palliative care

No.

Recommendations/Statements

GoR

LoE

Sources

11.12

All patients shall be offered palliative care (APV or SPV) after diagnosis of non-curable endometrial cancer, regardless of whether tumor-specific therapy is used.

A

1−

11.13

For patients with non-curable endometrial cancer, the complexity of the palliative situation shall be repeatedly assessed; this includes: the needs of the patient and her family, the patientʼs functional status and the disease phase.

EC

11.14

Patients with non-curable endometrial cancer and high complexity of their situation shall receive specialized palliative care.

S3-guideline “Palliative Medicine”: so">https://www.leitlinienprogramm-onkologie.de/leitlinien/palliativmedizin/

A

3

[85]


#

6.4  Rehabilitation

No.

Recommendations/Statements

GoR

LoE

Sources

11.15

Medical-oncological rehabilitation serves the specific treatment of disease and therapy sequelae. All patients with endometrial carcinoma shall be informed and advised about the legal options for applying for and receiving rehabilitation services.

EC

11.16

Therapy-related disorders, such as abdominal wall and adhesion discomfort, sexual dysfunction, pain during intercourse, vaginal dryness, urinary bladder and bowel dysfunction shall be inquired about and treated not only during primary therapy but also during rehabilitation and follow-up.

EC

11.17

Endometrial cancer patients should be informed about tumor-associated fatigue and screened systematically and repeatedly during the different treatment phases. Screening according to NCCN is recommended.

EC

11.18

If there is a value > 3 in the screening, there should be a diagnostic assessment for further clarification and specific advice on fatigue management and treatment if needed.

EC

11.19

For moderate or severe fatigue, moderate strength and endurance training should be provided based on physical performance level.

B

2

[85]

11.20

Psychoeducation or cognitive behavioral therapy should be offered for moderate or severe fatigue.

B

2

[85]

11.21

For moderate or severe fatigue, mindfulness-based stress reduction (MBSR) and yoga can be offered.

B

1

[86]

11.22

Yoga should be recommended to reduce fatigue in these patients.

B

1

[86]

11.23

Patients with stress urinary incontinence and/or fecal incontinence should be offered pelvic floor muscle training after endometrial cancer.

EC

11.24

If lymphedema is manifest, patients should be offered therapy after endometrial cancer according to the “S2k Guideline Diagnostics and Therapy of Lymphedema (AWMF Reg. No. 058-001) May 2017”.

EC


#
#
#
Zoom Image

#

Conflict of Interest/Interessenkonflikt

The conflicts of interest of the authors are listed in the long German-language version of the guideline.

Die Interessenkonflikte der Autoren sind in der Langfassung der Leitlinie aufgelistet.

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Correspondence/Korrespondenzadresse

Prof. Günter Emons
Universitätsmedizin Göttingen, Klinik für Gynäkologie und Geburtshilfe
Robert Koch Straße 40
37075 Göttingen
Germany   

Publication History

Received: 17 March 2023

Accepted after revision: 23 June 2023

Article published online:
15 August 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
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  • References/Literatur

  • 1 Travaglino A, Raffone A, Saccone G. et al. Significant risk of occult cancer in complex non-atypical endometrial hyperplasia. Arch Gynecol Obstet 2019; 300: 1147-1154
  • 2 Zaino R, Carinelli SG, Ellenson LH. et al. Tumours of the uterine Corpus: epithelial Tumours and Precursors. In: Kurman RJ, Carcangiu ML, Herrington CS, Young RH. eds. WHO Classification of Tumours of female reproductive Organs. 4th ed. Lyon: WHO Press; 2014: 125-126
  • 3 Antonsen SL, Ulrich L, Hogdall C. Patients with atypical hyperplasia of the endometrium should be treated in oncological centers. Gynecol Oncol 2011; 125: 124-128
  • 4 Gunderson CC, Fader AN, Carson KA. et al. Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review. Gynecol Oncol 2012; 125: 477-482
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