Geburtshilfe Frauenheilkd 2022; 82(02): 181-205
DOI: 10.1055/a-1671-2446
GebFra Science
Guideline/Leitlinie

Diagnosis, Therapy and Follow-up of Cervical Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry No. 032/033OL, May 2021) – Part 2 with Recommendations on Psycho-oncology, Rehabilitation, Follow-up, Recurrence, Palliative Therapy and Healthcare Facilities

Article in several languages: English | deutsch
Tanja Fehm
1   Universitätsklinikum Düsseldorf, Düsseldorf, Germany
,
Frederik A. Stübs
2   Universitätsklinikum Erlangen, Frauenklinik, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany
,
Martin C. Koch
2   Universitätsklinikum Erlangen, Frauenklinik, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany
,
Peter Mallmann
3   Universitätsklinikum Köln, Frauenklinik, Köln, Germany
,
Christian Dannecker
4   Universitätsklinikum Augsburg, Frauenklinik, Augsburg, Germany
,
Anna Dietl
2   Universitätsklinikum Erlangen, Frauenklinik, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany
,
Anna Sevnina
2   Universitätsklinikum Erlangen, Frauenklinik, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany
,
Franziska Mergel
2   Universitätsklinikum Erlangen, Frauenklinik, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany
,
Laura Lotz
2   Universitätsklinikum Erlangen, Frauenklinik, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany
,
Carolin C.Hack,
Anne Ehret
1   Universitätsklinikum Düsseldorf, Düsseldorf, Germany
,
Daniel Gantert
1   Universitätsklinikum Düsseldorf, Düsseldorf, Germany
,
Franca Martignoni
1   Universitätsklinikum Düsseldorf, Düsseldorf, Germany
,
Jan-Philipp Cieslik
1   Universitätsklinikum Düsseldorf, Düsseldorf, Germany
,
Jan Menke
5   SHG-Kliniken Völklingen, Klinik für Radiologie, Völklingen, Germany
,
Olaf Ortmann
6   Arbeitsgemeinschaft Deutscher Tumorzentren, Germany
,
Carmen Stromberger
7   Charité – Universitätsmedizin Berlin, Klinik für Radioonkologie und Strahlentherapie, Berlin, Germany
,
Karin Oechsle
8   Universitätsklinikum Hamburg-Eppendorf, II. Medizinische Klinik und Poliklinik, Hamburg, Germany
,
Beate Hornemann
9   Universitätsklinikum Dresden, Psychoonkologischer Dienst, Dresden, Germany
,
Friederike Mumm
10   Medizinische Klinik und Poliklinik III und Comprehensive Cancer Center (CCC München LMU), Klinikum der Universität München, LMU München, München, Germany
,
Christoph Grimm
11   Abteilung für allgemeine Gynäkologie und gynäkologische Onkologie, Gynecologic Cancer Unit, Comprehensive Cancer Center, Medizinische Universität Wien, Wien, Austria
,
Alina Sturdza
12   Universitätsklinikum AKH-Wien, Klinik für Radioonkologie, Wien, Austria
,
Edward Wight
13   Universitätsspital Basel, Frauenklinik, Basel, Switzerland
,
Kristina Loessl
14   Universitätsklinik Bern, Klinik für Radio-Onkologie, Bern, Switzerland
,
Michael Golatta
15   Universitätsklinikum Heidelberg, Frauenklinik, Heidelberg, Germany
,
Volker Hagen
16   St. Johannes Hospital Dortmund, Klinik für Innere Medizin II, Dortmund, Germany
,
Timm Dauelsberg
17   Universitätsklinikum Freiburg, Klinik für Onkologische Rehabilitation, Freiburg, Germany
,
Ingo Diel
18   Praxisklinik am Rosengarten, Mannheim, Germany
,
Karsten Münstedt
19   Klinikum Ortenau, Frauenklinik, Ortenau, Germany
,
Eberhard Merz
20   Zentrum für Ultraschalldiagnostik und Pränatalmedizin Frankfurt, Frankfurt am Main, Germany
,
Dirk Vordermark
21   Universitätsklinikum Halle (Saale), Klinik für Strahlentherapie, Halle (Saale), Germany
,
Katja Lindel
22   Städtisches Klinikum Karlsruhe, Klinik für Radioonkologie und Strahlentherapie, Karlsruhe, Germany
,
Christian Wittekind
23   Universitätsklinikum Leipzig, Institut für Pathologie, Leipzig, Germany
,
Volkmar Küppers
24   Frauenarztpraxis, Zytologisches Labor, Düsseldorf, Germany
,
Ralph Lellé
25   Universitätsklinikum Münster, Frauenklinik, Münster, Germany
,
Klaus Neis
26   Frauenärzte am Staden, Saarbrücken, Germany
,
Henrik Griesser
27   Labor Dr. Wisplinghoff, Köln, Germany
,
Birgit Pöschel
28   Praxis für Zytodiagnostik, Cölpin, Germany
,
Manfred Steiner
29   Frauenarztpraxis, Ihringen, Germany
,
Ulrich Freitag
30   Frauenarztpraxis, Wismar, Germany
,
Tobias Gilster
31   Frauenärzte am Stadtpark, Nürnberg, Germany
,
Alexander Schmittel
32   Onkologie Seestrasse, Praxis für Onkologie, Berlin, Germany
,
Michael Friedrich
33   Helios Klinikum Krefeld, Frauenklinik, Krefeld, Germany
,
Heidemarie Haase
34   Bundesverband Frauenselbsthilfe nach Krebs, Germany
,
Marion Gebhardt
34   Bundesverband Frauenselbsthilfe nach Krebs, Germany
,
Ludwig Kiesel
25   Universitätsklinikum Münster, Frauenklinik, Münster, Germany
,
Michael Reinhardt
35   Pius Hospital Oldenburg, Klinik für Nuklearmedizin, Oldenburg, Germany
,
Michael Kreißl
36   Universitätsklinikum Magdeburg, Klinik für Radiologie und Nuklearmedizin, Magdeburg, Germany
,
Marianne Kloke
37   Kliniken Essen-Mitte, Klinik für Palliativmedizin, Essen, Germany
,
Lars-Christian Horn
23   Universitätsklinikum Leipzig, Institut für Pathologie, Leipzig, Germany
,
Regina Wiedemann
38   Fliedner Fachhochschule Düsseldorf, Pflegewissenschaft, Düsseldorf, Germany
,
Simone Marnitz
39   Universitätsklinikum Köln, Klinik für Radioonkologie, Cyberknife- und Strahlentherapie, Köln, Germany
,
Anne Letsch
40   Universitätsklinikum Schleswig-Holstein, Klinik für Innere Medizin II, Kiel, Germany
,
Isabella Zraik
41   Kliniken Essen-Mitte, Klinik für Urologie, Essen, Germany
,
Bernhard Mangold
42   ZytoLabor Ludwigsburg, Ludwigsburg, Germany
,
Jochen Möckel
43   Labor Schneider, Freiburg im Breisgau, Germany
,
Céline Alt
44   Wolfgarten Radiologie Bonn, Bonn, Germany
,
Pauline Wimberger
45   Department of Gynecology and Obstetrics, Technische Universität Dresden and National Center for Tumor Diseases (NCT/UCC), Dresden, Germany
,
Peter Hillemanns
46   Medizinische Hochschule Hannover, Frauenklinik, Hannover, Germany
,
Kerstin Paradies
47   Konferenz onkologischer Kranken- und Kinderkrankenpflege (KOK), Germany
,
Alexander Mustea
48   Universitätsklinikum Bonn, Frauenklinik, Bonn, Germany
,
Dominik Denschlag
49   Hochtaunus Kliniken, Frauenklinik, Bad Homburg, Germany
,
Ulla Henscher
49   Hochtaunus Kliniken, Frauenklinik, Bad Homburg, Germany
,
Reina Tholen
50   Deutscher Verband für Physiotherapie (ZVK) e. V., Germany
,
Simone Wesselmann
51   Deutsche Krebsgesellschaft e. V., Berlin, Germany
,
Matthias W. Beckmann
2   Universitätsklinikum Erlangen, Frauenklinik, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany
› Author Affiliations
 

Abstract

Aim This is an update of the interdisciplinary S3-guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL), published in March 2021. The work on the updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Society of Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group on Gynecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie, AGO) of the German Cancer Society (Deutsche Krebsgesellschaft, DKG).

Method The process used to update the 2014 S3-guideline was based on an appraisal of the available evidence using the criteria of evidence-based medicine, adaptations of existing evidence-based national and international guidelines or – if evidence was lacking – on the consensus of the specialists involved in compiling the update. After an initial review of the current literature was carried out according to a prescribed algorithm, several areas were identified which, in contrast to the predecessor version from September 2014, required new recommendations or statements which would take account of more recently published literature and the recent appraisal of new evidence.

Recommendations The short version of this guideline consists of recommendations and statements on palliative therapy and follow-up of patients with cervical cancer. The most important aspects included in this updated guideline are the new FIGO classification published in 2018, the radical open surgery approach used to treat cervical cancer up to FIGO stage IB1, and the use of the sentinel lymph node technique for tumors ≤ 2 cm. Other changes include the use of PET-CT, new options in radiotherapy (e.g., intensity-modulated radiotherapy, image-guided adaptive brachytherapy), and drug therapies to treat recurrence or metastasis.


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I  Guideline Information

Publishing body

The German Guideline Program in Oncology of the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V., AWMF), the German Cancer Society (Deutsche Krebsgesellschaft e. V., DKG) and German Cancer Aid (Deutsche Krebshilfe, DKH).


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Guidelines program of the DGGG, OEGGG and SGGG

For more information, please refer to the end of this guideline.


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Guideline funding

This guideline was funded by German Cancer Aid (Deutsche Krebshilfe, DKH) as part of the German Guideline Program in Oncology.


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Citation format

Diagnosis, Therapy and Follow-up of Cervical Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry No. 032/033OL, May 2021) – Part 2 with Recommendations on Psycho-oncology, Rehabilitation, Follow-up, Recurrence, Palliative Therapy and Healthcare Facilities. Geburtsh Frauenheilk 2022; 82: 181 – 205


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Guideline documents

The complete long version in German, a version for patients and a slide version of this guideline, together with a list of the conflicts of interest of all of the authors are available on the homepage of the AWMF: https://www.awmf.org/leitlinien/detail/ll/032-033OL.html

The German-language version of the guideline is also available via the App of the German Guideline Program in Oncology: https://www.leitlinienprogramm-onkologie.de/app/


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Guideline authors

The organizations listed in [Tables 1] and [2] and their representatives were involved in the compilation of this guideline, and they are the authors of the guideline. The guideline was compiled with the direct involvement of a patient representative with voting rights. Physicians from the Oncology Competence Center of the National Association of Statutory Health Insurance Funds in Germany (GKV-Spitzenverband) and the Medical Advisory Service of German Health Insurance Funds (MDK-Gemeinschaft) were involved during the preparation of this guideline in an advisory capacity on various socio-medical aspects. They did not participate in the voting on individual recommendations and are not responsible for the contents of this guideline.

Tab. 1 Leading and/or coordinating guideline author.

Author

AWMF professional society

Prof. Dr. Matthias W. Beckmann

German Society of Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe e. V., DGGG); Working Group on Gynecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie e. V., AGO)

Prof. Dr. Tanja Fehm

German Society of Gynecology and Obstetrics (DGGG)

Tab. 2 Contributing guideline authors.

Author

Mandate holder

DGGG working group (AG)/
AWMF/non-AWMF professional society/organization/association

Prof. Dr. Jan Menke

Imaging in Oncology Working Group (Arbeitsgemeinschaft Bildgebung in der Onkologie, ABO)

Prof. Dr. Olaf Ortmann

Working Group of German Tumor Centers (Arbeitsgemeinschaft Deutscher Tumorzentren, ADT)

PD Dr. Carmen Stromberger

Proxy: Prof. Dr. Karin Oechsle

Working Group for Palliative Medicine (Arbeitsgemeinschaft für Palliativmedizin, APM)

Dipl.-Psych. Beate Hornemann

Proxy: Dr. Friederike Mumm

Working Group for Psychooncology (Arbeitsgemeinschaft für Psychoonkologie, PSO)

Prof. Dr. Peter Mallmann (senior coordinator)

Prof. Dr. Tanja Fehm (mandate holder)

Working Group on Gynecological Oncology (AGO)

Prof. Dr. Christoph Grimm (mandate holder)

Dr. Alina Sturdza (deputy)

Working Group on Gynecological Oncology of the Austrian Society of Gynecology and Obstetrics (Arbeitsgemeinschaft Gynäkologische Onkologie der Österreichischen Gesellschaft für Gynäkologie und Geburtshilfe, AGO der OEGGG)

PD Dr. Edward Wight (mandate holder)

Dr. Kristina Loessl (deputy)

Working Group on Gynecological Oncology of the Swiss Society of Gynecology and Obstetrics (Arbeitsgemeinschaft Gynäkologische Onkologie der Schweizer Gesellschaft für Gynäkologie und Geburtshilfe, AGO der SGGG)

Prof. Dr. Michael Golatta (until 03/20)

Working Group on Gynecological Radiology (Arbeitsgemeinschaft für gynäkologische Radiologie, AGR)

Dr. Volker Hagen

Working Group on Internal Oncology (Arbeitsgemeinschaft Internistische Onkologie, AIO)

Dr. Timm Dauelsberg (mandate holder)

Prof. Dr. Ingo Diel (deputy)

Working Group on Oncological Rehabilitation and Social Medicine (Arbeitsgemeinschaft Onkologische Rehabilitation und Sozialmedizin, AGORS)

Prof. Dr. Ingo Diel

Working Group on Supportive Measures in Oncology (Arbeitsgemeinschaft Supportive Maßnahmen in der Onkologie, AGSMO)

Prof. Dr. Karsten Münstedt

Working Group on Prevention and Integrative Oncology (Arbeitsgemeinschaft Prävention und integrative Onkologie, PRIO)

Prof. Dr. Eberhard Merz

Working Group on Ultrasound Diagnostics in Gynecology and Obstetrics, (Arbeitsgemeinschaft für Ultraschalldiagnostik in Gynäkologie und Geburtshilfe, ARGUS)

Prof. Dr. Dirk Vordermark (mandate holder)

Prof. Dr. Katja Lindel (deputy)

Working Group on Radiological Oncology (Arbeitsgemeinschaft Radiologische Onkologie, ARO)

Prof. Dr. Christian Wittekind

Working Group on Tumor Classification in Oncology (Arbeitsgemeinschaft Tumorklassifikation in der Onkologie, ATO)

PD Dr. Volkmar Küppers (mandate holder)

Prof. Dr. Ralph Lellé (deputy)

Working Group on Cervical Pathology and Colposcopy (Arbeitsgemeinschaft Zervixpathologie und Kolposkopie, AG-CPC)

Prof. Dr. med. Klaus Joachim Neis (up until August 31, 2019)

Prof. Dr. Henrik Griesser (from September 1, 2019)

Professional Association of German Physicians Working in Cytology (Arbeitsgemeinschaft zytologisch tätiger Ärzte in Deutschland, AZÄD)

Birgit Pöschel

Federal Association of German Pathologists (Bundesverband Deutscher Pathologen e. V., BDP)

Dr. Manfred Steiner (mandate holder)

Dipl.-Med. Ulrich Freitag (deputy)

Professional Association of Gynecologists in Germany (Berufsverband der Frauenärzte, BVF)

Tobias Gilster

Professional Association of Gynecological Oncologists in Private Practice in Germany (Berufsverband Niedergelassener Gynäkologischer Onkologen in Deutschland, BNGO)

PD Dr. Alexander Schmittel

Professional Association of Hematologists in Private Practice (Berufsverband der niedergelassenen Hämatologen, BNHO)

Prof. Dr. Michael Friedrich

Federal Working Group of Senior Doctors in Gynecology and Obstetrics (Bundesarbeitsgemeinschaft Leitender Ärztinnen und Ärzte in der Frauenheilkunde und Geburtshilfe, BLFG)

Heidemarie Haase (mandate holder)

Marion Gebhardt (deputy)

Federal Association of Womenʼs Self-help After Cancer (Bundesverband Frauenselbsthilfe nach Krebs, FSH)

Prof. Dr. Ludwig Kiesel

German Society of Endocrinology (Deutsche Gesellschaft für Endokrinologie, DGE)

Prof. Dr. Matthias W. Beckmann (guideline coordinator)

Prof. Dr. Christian Dannecker (mandate holder)

German Society of Gynecology and Obstetrics (DGGG)

Prof. Dr. Michael Reinhardt (mandate holder)

Prof. Dr. Michael Kreißl (deputy)

German Society for Nuclear Medicine (Deutsche Gesellschaft für Nuklearmedizin, DGN)

Dr. Marianne Kloke

German Society for Palliative Medicine (Deutsche Gesellschaft für Palliativmedizin, DGP)

Prof. Dr. Lars-Christian Horn

German Society for Pathology (Deutsche Gesellschaft für Pathologie, DGP)

Prof. Dr. Regina Wiedemann

German Society for Nursing Science (Deutsche Gesellschaft für Pflegewissenschaft, DGP)

Prof. Dr. Simone Marnitz-Schulze

German Society for Radiooncology (Deutsche Gesellschaft für Radioonkologie, DEGRO)

Prof. Dr. Eberhardt Merz

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

Prof. Dr. Anne Letsch

German Society for Hematology and Oncology (Deutsche Gesellschaft für Hämatologie und Onkologie, DGHO)

Dr. Isabella Zraik

German Society for Urology (Deutsche Gesellschaft für Urologie, DGU)

Dr. Bernhard Mangold (mandate holder)

Dr. Jochen Möckel (deputy)

German Society for Cytology (Deutsche Gesellschaft für Zytologie, DGZ)

PD Dr. Céline Alt

German X-Ray Society (Deutsche Röntgengesellschaft, DRG)

Prof. Dr. Pauline Wimberger

European Society for Gynaecological Oncology (ESGO)

Prof. Dr. Peter Hillemanns

Complementary Guideline on Screening, Certification Commission for Gynecological Cancer Centers (Zertifizierungskommission gynäkologischer Krebszentren)

Kerstin Paradies

Conference on Oncology Nursing and Pediatric Nursing (Konferenz onkologischer Kranken- und Kinderkrankenpflege, KOK)

Prof. Dr. Alexander Mustea

North-Eastern German Society for Gynecological Oncology (Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie, NOGGO)

Prof. Dr. Dominik Denschlag

Study Group of the Gynecological Oncology Working Group (Studiengruppe der Arbeitsgemeinschaft Gynäkologische Onkologie, AGO)

Ulla Henscher (mandate holder)

Reina Tholen (deputy)

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

Methodological supervision and support were provided by Office of the German Guideline Program in Oncology and the AWMF ([Table 3]). The guideline authors were supported by the project team and the Guidelines Office ([Table 4]).

Tab. 3 Methodological supervision and support.

Name

City

Dr. Markus Follmann MPH M. Sc. (Office of the German Guideline Program in Oncology – German Cancer Society)

Berlin

Dipl.-Soz. Wiss. Thomas Langer (Office of the German Guideline Program in Oncology – German Cancer Society)

Berlin

Dr. Monika Nothacker MPH (Deputy Head – AWMF Institute for for Medical Knowledge Management)

Berlin

PD Dr. Simone Wesselmann, MBA (German Cancer Society – certification, quality indicators)

Berlin

Biologist Gregor Wenzel

Berlin

Tab. 4 Guideline Office and project team.

Name

City

Dr. Martin C. Koch (Guideline Office)

Erlangen

Dr. Frederik A. Stübs (Guideline Office)

Erlangen

Dr. Anna K. Dietl (project team)

Erlangen

Anna Sevnina (project team)

Erlangen

Dr. Franziska Mergel (project team)

Erlangen

PD Dr. Laura Lotz (project team)

Erlangen

PD Dr. Carolin C. Hack (project team)

Erlangen

Dr. Anne Ehret (project team)

Düsseldorf

Dr. Daniel Gantert (project team)

Düsseldorf

Dr. Franca Martignoni (project team)

Düsseldorf


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Abbreviations

AIS: adenocarcinoma in situ
CAM: complementary and alternative medicine
CHT: chemotherapy
CI: confidence interval
CIN: cervical intraepithelial neoplasia
CT: computed tomography
EC: expert consensus
FIGO: Fédération Internationale de Gynécologie et dʼObstétrique (International Federation of Gynecology and Obstetrics)
GKV: statutory health insurance in Germany (Gesetzliche Krankenversicherung)
GoR: grade of recommendation
HE: hysterectomy
HPV: human papillomavirus
ICG: indocyanine green
IECC: International Endocervical Adenocarcinoma Classification
LoE: level of evidence
MDK: Medical Advisory Service of the German Association of Health Insurance Funds (Medizinischer Dienst der Krankenkassen)
MRI: magnetic resonance imaging
NECC: neuroendocrine cervical carcinoma
Pap: cervical cytology by Pap smear
PET: positron emission tomography
R(CH)T: simultaneous radio(chemo)therapy
SMILE: stratified mucin-producing intraepithelial lesion
SNB: sentinel lymph node biopsy
STIKO: German Standing Committee on Vaccinations at the Robert Koch Institute
TNM: tumor–nodes–metastasis
UICC: Union internationale contre le cancer


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II  Guideline Application

Purpose and objectives

The rationale for this guideline was the problems relating to security of care as well as the fact that mortality and morbidity rates have not decreased much in the last 15 years and the current therapies administered to patients with cervical cancer vary greatly. The aim of this updated guideline remains the same as that of the previous version from 2014. This guideline “Diagnosis, Therapy and Follow-up of Cervical Cancer” is an evidence- and consensus-based instrument for the care of patients with cervical cancer. It provides patients with scientific, up-to-date, economically viable procedures for diagnosis, therapy, follow-up and rehabilitation which are appropriate for the various stages of disease. The current version of the guideline aims to provide a basis for clinical decision-making on appropriate treatment. The guideline also incorporates the concept of shared decision-making.


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Targeted areas of patient care

The area covered by the guideline ranges from diagnosis to therapy and the follow-up of patients with cervical cancer and includes patients with microinvasive lesions/high-grade precursor lesions (but excludes patients with early precursor lesions/preinvasive lesions). The scope of the guideline is intersectoral. It covers outpatient and in-patient care as well as rehabilitation.


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Target user groups

This S3-guideline is aimed at all patients with cervical cancer (including microinvasive lesions/high-grade precursor lesions but excluding early precursor lesions/preinvasive lesions) and their families.


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Intended audience

The recommendations of the guideline are for all physicians and professional groups involved in the outpatient and/or in-patient care and rehabilitation of patients with cervical cancer.

The guideline is also intended for

  • medical and scientific specialist societies and professional associations,

  • special interest groups for women (womenʼs health organizations, patient organizations, and self-help organizations),

  • quality assurance institutions and federal and state-level projects (e.g., AQUA, ADT, IQWiG, GEKID, gesundheitsziele.de, IQTIG),

  • health policy institutions and decision-making bodies at federal and state levels,

  • certification institutions (e.g., DKG),

  • funding bodies.


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Adoption and period of validity

The validity of this guideline was confirmed by the executive boards/heads of the participating medical professional societies, working groups, organizations and associations as well as by the boards of the DGGG, SGGG and OEGGG and the DGGG/OEGGG/SGGG guidelines commission and was thus approved in its entirety. This guideline is valid until October 2025. Because of the contents of this guideline, this period of validity is only an estimate. If changes are urgently required, then the guideline can be updated earlier; if the information in the guideline still represents the current state of knowledge, then the guidelineʼs period of validity can be extended.


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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 has been classified as: S3.

The methodological approach used to compile this guideline is described in the guideline report which is freely available on the homepage of the German Guideline Program in Oncology (https://www.leitlinienprogramm-onkologie.de/leitlinien/zervixkarzinom/) and the homepage of the AWMF (http://www.awmf.org/).


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Grading of evidence based on SIGN

To classify the risk of bias in identified studies, this guideline used the system of the Scottish Intercollegiate Guidelines Network (SIGN) described in [Table 5] (cf. https://www.sign.ac.uk/media/1050/sign50_2019.pdf).

Tab. 5 Classification of levels of evidence according to SIGN.

Level

Description

1++

High-quality meta-analyses, systematic review of RCTs, or RCTs with a very low risk of bias.

1+

Well-conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias.

1−

Meta-analyses, systematic reviews, or RCTs with a high risk of bias.

2++

High-quality systematic reviews of case-control or cohort studies,

or

High-quality case-control or cohort studies with a very low risk of confounding, bias or “chance” and a high probability that the relationship is causal.

2+

Well-conducted case-control studies or cohort studies with a low risk of confounding, bias or “chance” and a moderate probability that the relationship is causal.

2−

Case-control studies or cohort studies with a high risk of confounding, bias or “chance” and a significant risk that the relationship is not causal.

3

Non-analytical studies, e.g., case reports, case series.

4

Expert opinion


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Grading of recommendations

This guideline indicates the level of evidence (based on the SIGN classification) of underlying studies and, if recommendations are made, the strength of the recommendation (grade of recommendation) for all evidence-based statements and recommendations. As regards the strength of the recommendation, the guideline differentiates between three levels of recommendation ([Table 6]), with the level reflected in the wording used in the respective recommendation, as shown below.

Tab. 6 Grade of recommendation.

Symbol

Description of level of obligation to comply with the recommendation

Terminology

A

Strong recommendation, highly binding

must/must not

B

Recommendation, moderately binding

should/should not

0

Open recommendation, not binding

may/may not

In principle, the grade of recommendation is based on the strength of the available evidence. For example, if there is a high level of evidence (e.g., provided by high-quality meta-analyses/systematic reviews of RCTs or several methodologically high-quality RCTs), then a strong recommendation is given (grade of recommendation: A, “must”).

But the following criteria are also taken into account and can result in the level of recommendation being upgraded or downgraded:

Consistency of study results

  • Example: The effect estimates for study results diverge, showing no consistent tendency.

Clinical relevance of endpoints and effect sizes

  • Example: Even though there are a number of studies with results which point in a specific direction, the importance of the selected endpoints and/or effect sizes are not considered relevant.

Benefit-to-risk ratio

  • Example: Although the intervention has a proven benefit, it is also associated with a relevant harm which mitigates against giving an unqualified recommendation.

Ethical obligations

  • Example: Downgrading: For ethical reasons, an intervention with a proven benefit cannot be unreservedly offered to patients. Upgrading: Strong recommendation based on case-control studies, because an RCT cannot be carried out for ethical reasons.

Patient preferences

  • Example: An intervention with a proven benefit is not strongly recommended as it is rejected by patients who consider it to be onerous or not feasible.

Applicability, practicability of care

  • Example: An intervention with proven positive effects cannot be recommended because structural reasons mean that it is not available in regional healthcare systems.


#

Statements

Statements are expositions or explanations of specific facts, circumstances or problems which do not directly call for action. They are adopted following a formal consensus procedure using the same approach used for recommendations, and they may be based either on study results or on expert opinions.


#

Achieving consensus and strength of consensus

At structured NIH-type (S2k/S3 level) consensus conferences, authorized participants attending the conference vote on draft statements and recommendations. Conferences are structured as follows: a recommendation is presented; participants can ask questions about the contents of the recommendation; amendments can be proposed; all proposed amendments are voted on. If a consensus (> 75% of votes) cannot be reached, there is another round of discussions, followed by another vote. At the end of the session, the strength of the consensus is determined based on the number of persons who participated in the session ([Table 7]).

Tab. 7 Strength of consensus based on the extent of consensus.

Symbols

Level of consensus

Extent of agreement in percent

+++

Strong consensus

> 95% of participants agree

++

Consensus

> 75 – 95% of participants agree

+

Majority agreement

> 50 – 75% of participants agree

No consensus

< 51% of participants agree


#

Expert consensus

When the guideline authors decide to make statements/recommendations based on the expert consensus of the guideline authors, such statements/recommendations are identified by the phrase “expert consensus” (EC). No symbols are used to grade such recommendations; the strength of the expert consensus is indicated by the wording used (must/should/may) in accordance with the grading shown in [Table 6].


#
#

IV  Guideline

1  Supportive therapy

Supportive therapy is an integral part of the treatment concept. There may be side effects in the form of acute changes which occur during or immediately following treatment or appear as late sequelae. There is a DACH S3-guideline “Supportive Therapy for Oncological Patients” (long version 1.3 – February 2020, AWMF registry no. 032/054OL) on the supportive care for cancer patients [1].

No.

Recommendations/Statements

GoR

LoE

Sources

12.1.

reviewed 2021

Consensus-based recommendation

Supportive therapy for prophylaxis against and minimization of treatment-related or tumor-related symptoms must be administered in accordance with guidelines.

EC


#

2  Psycho-oncology and Quality of Life

2.1  Psycho-oncological support

No.

Recommendations/Statements

GoR

LoE

Sources

13.1.

reviewed 2021

Consensus-based statement

Psycho-oncological care for patients with cervical carcinoma is an integral component of oncological diagnosis, treatment, and follow-up and represents an interdisciplinary task.

EC

13.2.

reviewed 2021

Consensus-based recommendation

Psycho-oncological advice and support must be offered to all patients and their relatives in a manner appropriate to their needs.

EC

13.3.

reviewed 2021

Consensus-based recommendation

Individual needs and the corresponding advice and treatment must be ascertained using a standardized screening procedure, in accordance with the Level 3 guideline “Psycho-oncological Diagnosis, Advice, and Treatment in Cancer Patients” (AWMF register no. 032/051OL; version 1, January 1, 2014).

EC

13.4.

reviewed 2021

Consensus-based recommendation

The subject of sexuality should be actively explored in order to ascertain what further assistance may be needed and initiate the corresponding support measures.

EC

13.5.

reviewed 2021

Consensus-based recommendation

Psychosocial assistance should be offered with a low threshold to all patients and their relatives in every phase of the disease.

EC


#

2.2  Measuring quality of life

No.

Recommendations/Statements

GoR

LoE

Sources

13.6.

reviewed 2021

Consensus-based recommendation

Research on the quality of life in patients with cervical carcinoma must be carried out both in clinical studies and also in nursing-care research.

EC


#
#

3  Integrative Medicine

3.1  Counselling about complementary and alternative medicine (CAM)

No.

Recommendations/Statements

GoR

LoE

Sources

14.1.

reviewed 2021

Consensus-based recommendation

Advice on complementary and alternative medicine (CAM) should be given to patients. If patients make use of such methods, it should be documented.

EC


#

3.2  Importance of alternative medicine

No.

Recommendations/Statements

GoR

LoE

Sources

14.2.

reviewed 2021

Consensus-based recommendation

Alternative medicine treatment options – i.e., measures that attempt to treat women who have cervical carcinoma while avoiding the methods of conventional medicine – must be rejected.

EC


#
#

4  Rehabilitation

No.

Recommendations/Statements

GoR

LoE

Sources

15.1.

reviewed 2021

Consensus-based recommendation

The purpose of medical oncological rehabilitation is to provide specific treatment for the sequelae of the disease and of its treatment. All patients must receive information and advice about the statutory options available for applying for and using rehabilitation measures.

EC

15.2.

reviewed 2021

Consensus-based recommendation

Treatment-related disturbances must be inquired after and treated during rehabilitation.

EC

4.1  Physiotherapy treatment during rehabilitation

No.

Recommendations/Statements

GoR

LoE

Sources

15.3.

reviewed 2021

Evidence-based recommendation

In case of stress urinary incontinence and/or fecal incontinence, patients with cervical carcinoma should be offered pelvic floor training.

B

1++

[2] – [8]


#

4.2  Treatment of lymphedema during rehabilitation

No.

Recommendations/Statements

GoR

LoE

Sources

15.4.

reviewed 2021

Consensus-based recommendation

In case of manifest lymphedema, combined therapy with skin care, manual lymph drainage, therapeutic exercises, and compression should be offered.

EC


#

4.3  Treatment of fatigue syndrome during rehabilitation

No.

Recommendations/Statements

GoR

LoE

Sources

15.5.

reviewed 2021

Evidence-based recommendation

In case of fatigue, patients should be offered forms of active training (strength training and/or stamina training).

B

1++

[9] – [11]


#
#

5  Follow-up

Follow-up of patients with cervical cancer starts when surgical and/or radiochemotherapy has been completed. Follow-up includes taking the patientʼs medical history, a physical examination, and a medical consultation and support. If suspicious findings are detected at follow-up or if there is a clinical suspicion of disease, diagnostic imaging should be carried out based on the symptoms to detect locoregional or distant recurrence [12] – [18].

No.

Recommendations/Statements

GoR

LoE

Sources

16.1.

reviewed 2021

Consensus-based recommendation

The following points should be mentioned in discussions with the patient during the follow-up:

  • Temporary and long-term effects of the disease and treatment

  • Assistance available (self-help groups, psychosocial cancer advice services)

  • Psycho-oncological/psychotherapeutic treatment options

  • Sexuality and partnership

  • Quality of life

EC

5.1  Follow-up without suspicion of recurrence

No.

Recommendations/Statements

GoR

LoE

Sources

16.2.

reviewed 2021

Consensus-based recommendation

Obligatory examinations should be carried out every 3 months for 3 years, and then every 6 months for a further 2 years. These include patient history, rectovaginal examination, speculum examination, and cytology.

EC

16.3.

reviewed 2021

Consensus-based recommendation

Optional examinations can be carried out if there are clinically unremarkable findings (in asymptomatic patients). These include colposcopy, HPV testing, vaginal ultrasonography of the lesser pelvis, and ultrasonography of the urinary tract.

EC


#

5.2  Tumor markers

No.

Recommendations/Statements

GoR

LoE

Sources

16.4.

reviewed 2021

Consensus-based recommendation

Routine controls of tumor markers to diagnose recurrences must not be carried out.

EC


#

5.3  Expanded diagnostic workup for suspicion of recurrence

No.

Recommendations/Statements

GoR

LoE

Sources

16.5.

reviewed 2021

Consensus-based recommendation

If a locoregional recurrence is suspected, histological confirmation must be obtained.

EC


#

5.4  HPV vaccination after conization

No.

Recommendations/Statements

GoR

LoE

Sources

16.6.

reviewed 2021

Consensus-based statement

The significance of prophylactic HPV vaccination after the completion of treatment for cervical carcinoma is unclear.

EC


#
#

6  Local Recurrence

The rate of recurrence for cervical cancer for all tumor stages and forms of therapy is between 22 and 31% [19], [20]. Known risk factors for local/locoregional recurrence are the FIGO stage (tumor diameter, parametrial tumor invasion, metastatic involvement of pelvic lymph nodes), younger age (< 45 years), the histological subtype, and lymphatic invasion L1 [20] – [24].

6.1  Diagnosing local recurrence

No.

Recommendations/Statements

GoR

LoE

Sources

17.1.

reviewed 2021

Consensus-based recommendation

If a local recurrence develops, the appropriate imaging diagnostic procedures must be carried out to exclude distant metastases and for treatment planning.

EC


#

6.2  Treatment of local recurrence

No.

Recommendations/Statements

GoR

LoE

Sources

17.2.

reviewed 2021

Consensus-based recommendation

With local recurrences, treatment decisions should be based on the following points:

  • Patientʼs general condition (comorbidities)

  • Location and extent of the local recurrence

  • Presence of distant metastases

  • Extent of metastasis development

  • Type of primary therapy/prior therapies

  • Patientʼs request

EC

6.2.1  Treatment of central tumor recurrence after first-line surgical treatment

No.

Recommendations/Statements

GoR

LoE

Sources

17.3.

reviewed 2021

Consensus-based statement

In case of a central recurrence in a patient who has not previously undergone radiotherapy, exenteration or radiochemotherapy are possible.

EC

17.4.

reviewed 2021

Consensus-based recommendation

Due to its lower morbidity, radiochemotherapy should be carried out in patients with no previous radiotherapy who develop a recurrence.

EC

17.5.

reviewed 2021

Consensus-based recommendation

Exenteration must only be carried out in cases of recurrence if resection with healthy margins appears possible and there are no distant metastases.

EC


#

6.2.2  Treatment of pelvic wall recurrence after first-line or adjuvant radio-/radiochemotherapy

No.

Recommendations/Statements

GoR

LoE

Sources

17.6.

reviewed 2021

Consensus-based recommendation

Repeat radiotherapy at a curative dosage must not be administered in the previously irradiated volume.

EC


#

6.2.3  Palliative treatment of local recurrence (when margin-negative surgery is not possible)

No.

Recommendations/Statements

GoR

LoE

Sources

17.7.

reviewed 2021

Consensus-based recommendation

A surgical intervention can be carried out with palliative intent for a local recurrence, to relieve tumor-specific symptoms.

EC

17.8.

reviewed 2021

Consensus-based recommendation

A radiotherapeutic intervention can be carried out with palliative intent for a local recurrence that is not operable with healthy margins, to relieve tumor-specific symptoms.

EC


#
#
#

7  Distant Metastasis

7.1  Therapy options for distant metastasis

7.1.1  Isolated metastasis

No.

Recommendations/Statements

GoR

LoE

Sources

18.1.

reviewed 2021

Consensus-based recommendation after systematic research

With an isolated metastasis, the option of local therapy in the form of surgery, local irradiation, or locally destructive treatment procedures should be considered on an interdisciplinary basis at the tumor conference.

EC


#

7.1.2  Disseminated metastases

No.

Recommendations/Statements

GoR

LoE

Sources

18.2.

reviewed 2021

Evidence-based statement

With disseminated metastases or metastases that are not accessible for local therapy, there is an indication for administering palliative drug therapy.

ST

1+

[25] – [27]

18.3.

mod. 2021

Evidence-based recommendation

Palliative drug therapy should be administered in the form of platinum-containing combination chemotherapy.

B

1+

[25] – [28]


#

7.1.3  Systemic therapies in the metastatic setting

No.

Recommendations/Statements

GoR

LoE

Sources

18.4.

mod. 2021

Evidence-based recommendation

Following radio(chemo)therapy with cisplatin as a “radiosensitizer,” cisplatin administration can be repeated.

In recurrences/metastases after prior chemotherapy with cisplatin, repeat administration of cisplatin can be carried out in combination with topotecan, paclitaxel, gemcitabine, or vinorelbine, or carboplatin can be administered with paclitaxel.

0

1+

[25], [28], [29]

18.5.

reviewed 2021

Evidence-based statement

Combination therapies are associated with higher rates of morbidity and toxicity than the monotherapy.

Combination therapies have a better response rate.

In relation to overall survival, a slight absolute survival benefit has so far only been demonstrated for the combination of cisplatin with topotecan.

ST

1+

[25], [26], [30]

18.6.

new in 2021

Evidence-based recommendation

As an alternative to cisplatin, carboplatin can also be used in monotherapy and combination therapy.

0

1+

[28], [29]

18.7.

new in 2021

Evidence-based recommendation

Cisplatin should be preferred in patients who have not previously received it.

B

1−

[28]

7.1.3.1  Targeted therapy

No.

Recommendations/Statements

GoR

LoE

Sources

18.8.

mod. 2021

Evidence-based recommendation

Patients with metastatic or recurrent/persistent cervical cancer should receive concurrent bevacizumab – independently of prior treatment with radio(chemo)therapy – for first-line palliative chemotherapy with cisplatin/paclitaxel or topotecan/paclitaxel.

B

1+

[31]


#

7.1.3.2  Second-line therapies for cervical cancer

No.

Recommendations/Statements

GoR

LoE

Sources

18.9.

new in 2021

Consensus-based statement

In patients with PD-L1-positive metastatic cervical carcinoma, checkpoint inhibitors are another therapeutic option.

EC


#
#
#
#

8  Palliative Medical Support

Detailed information can be found in the S3-guideline “Palliative Medicine for Patients with Incurable Cancer” (AWMF registry no. 128/001OL) [32]. The statements below were taken from the above-mentioned guideline.

No.

Recommendations/Statements

GoR

LoE

Sources

19.1.

reviewed 2021

Evidence-based recommendation from the Level 3 guideline on palliative medicine (AWMF register no. 128/001OL, version 2.1, January 2020)

Following a diagnosis of incurable cancer, all patients must be offered palliative care, regardless of whether tumor-specific therapy is being provided.

A

1−

[32] – [40]

19.2.

reviewed 2021

Consensus-based recommendation from the Level 3 guideline on palliative medicine (AWMF register no. 128/001OL, version 2.1, January 2020)

In the case of incurable cancer, the physical, psychological, social, and spiritual needs, as well as burdens and information requirements, of patients and their relatives must be assessed repeatedly and reassessed again if the clinical situation changes.

EC

19.3.

reviewed 2021

Evidence-based recommendation from the Level 3 guideline on palliative medicine (AWMF register no. 128/001OL, version 2.1, January 2020)

Patients with incurable cancer and a highly complex situation must receive specialized palliative care.

A

1−

[37], [38], [40]


#
#

9  The Wish to Have Children

The recommendations in this chapter are based on expert opinions as well as the current S2k guideline on preserving the fertility of patients with oncological disease (AWMF registry number: 015/082; version 1.0; September 2017), as the data are not sufficient for an evidence-based recommendation [41]. For more information on fertility preservation methods and their success rates, please refer to the S2k guideline mentioned here.

No.

Recommendations/Statements

GoR

LoE

Sources

20.1.

new in 2021

Consensus-based recommendation

Women with early-stage cervical cancer who wish to have children must be offered fertility-preserving treatment options.

EC

10  Cervical Cancer in Pregnancy

The published incidence of cervical cancer in pregnancy is low and lies between 0.02 and 0.9% [42].

No.

Recommendations/Statements

GoR

LoE

Sources

21.1.

reviewed 2021

Evidence-based recommendation

During pregnancy, any cytological suspicion of higher-grade dysplasia or carcinoma must be clarified using colposcopy and biopsy.

A

2+

[43]


#

11  Incidental Cervical Cancer After Simple Hysterectomy

No.

Recommendations/Statements

GoR

LoE

Sources

22.1.

reviewed 2021

Consensus-based recommendation

In cases of incidental cervical carcinoma after simple hysterectomy, stage-appropriate treatment must be administered. If a radical hysterectomy would originally have been indicated, surgical staging must be carried out, followed by either repeat surgery (parametria, vaginal cuff, lymphadenectomy) or radio(chemo)therapy.

EC


#

12  Neuroendocrine Cervical Carcinoma

Neuroendocrine cervical carcinoma (NECC) is a particularly rare but very high-risk form of cervical cancer with an incidence of around 1 – 1.5% of all cervical cancers. Overall, NECC has a poor prognosis, irrespective of the therapy administered, and has a poorer prognosis than adenocarcinoma or squamous cell carcinoma [44] – [49]. Already in the early stages of disease (I to IIA), 40 – 60% of patients develop regional lymph node metastasis or hematogenous distant metastasis. The 5-year survival rate is between 34 – 37%, with a mean overall survival of 40 months [50], [51]. The most common therapy used to treat early-stage disease (FIGO I–IIA) is radical hysterectomy, optionally followed by adjuvant chemotherapy (or a first-line neoadjuvant concept), and this appears to have the best survival rates [50], [51]. Because of its histological similarity to small cell bronchial carcinoma (SCLC), treatment often consists of chemotherapy with etoposide and cisplatin/carboplatin (PE) or vincristine, adriamycin and cyclophosphamide (VAC) [50], [51]. Treatment of locally advanced NECC (IIB–IVB) or recurrence consists of combined radiochemotherapy or chemotherapy [50], [51]. To facilitate therapy planning, cases may be presented to specialist tumor boards for neuroendocrine tumors.


#

13  Healthcare Facilities

13.1  Treatment in oncological centers

No.

Recommendations/Statements

GoR

LoE

Sources

24.1.

reviewed 2021

Consensus-based recommendation

Patients with cervical carcinoma should be treated by an interdisciplinary team. The team should include all of the specialist disciplines necessary, in a cross-sectoral network. This is best achieved in a certified center.

EC

After the gynecological examination has been carried out, the patient will need to undergo further histological investigation if results of the cytological pap smear and/or HPV test are abnormal, with further examinations carried out either at a local center with the appropriate expertise or in a certified gynecological dysplasia clinic/unit ([Fig. 1]).

Zoom Image
Abb. 1 Agreed care algorithm (reviewed in 2021). [rerif]

13.1.1  Center concept – interdisciplinary tumor board

No.

Recommendations/Statements

GoR

LoE

Sources

24.2.

reviewed 2021

Consensus-based recommendation

The cases of all patients with cervical carcinoma must be presented at an interdisciplinary tumor conference.

EC


#

13.1.2  Advanced training options

No.

Recommendations/Statements

GoR

LoE

Sources

24.3.

reviewed 2021

Consensus-based recommendation

Education and further training for physicians in the treatment of patients with cervical carcinoma should take place in a gynecological cancer center/oncological center.

EC


#
#
#
#
Zoom Image

#

Conflict of Interest/Interessenkonflikt

The conflicts of interest of all the authors are listed in the long German-language version of the guideline report./Die Interessenkonflikte der Autoren sind im Leitlinienreport aufgelistet.


Correspondebce/Korrespondenzadresse

Prof. Dr. med. Matthias Beckmann
Universitätsklinikum Erlangen
Frauenklinik
Universitätsstraße 21 – 23
91054 Erlangen
Germany   

Publication History

Received: 29 September 2021
Received: 14 October 2021

Accepted: 17 October 2021

Article published online:
11 February 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany


Zoom Image
Abb. 1 Agreed care algorithm (reviewed in 2021). [rerif]
Zoom Image
Zoom Image
Abb. 1 Konsentierter Versorgungsalgorithmus (geprüft 2021). [rerif]
Zoom Image