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DOI: 10.1055/a-1671-2446
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- Abstract
- I Guideline Information
- II Guideline Application
- III Methodology
- IV Guideline
- 9 The Wish to Have Children
- References/Literatur
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.
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) |
Author Mandate holder |
DGGG working group (AG)/ |
---|---|
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]).
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 |
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
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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
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medical and scientific specialist societies and professional associations,
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special interest groups for women (womenʼs health organizations, patient organizations, and self-help organizations),
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quality assurance institutions and federal and state-level projects (e.g., AQUA, ADT, IQWiG, GEKID, gesundheitsziele.de, IQTIG),
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health policy institutions and decision-making bodies at federal and state levels,
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certification institutions (e.g., DKG),
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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).
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.
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
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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
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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
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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
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Example: An intervention with proven positive effects cannot be recommended because structural reasons mean that it is not available in regional healthcare systems.
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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.
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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]).
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 |
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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].
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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].
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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 |
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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 |
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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 |
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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 |
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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 |
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2.2 Measuring quality of life
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3 Integrative Medicine
3.1 Counselling about complementary and alternative medicine (CAM)
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3.2 Importance of alternative medicine
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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 |
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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
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4.2 Treatment of lymphedema during rehabilitation
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4.3 Treatment of fatigue syndrome during rehabilitation
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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:
|
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 |
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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 |
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5.2 Tumor markers
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5.3 Expanded diagnostic workup for suspicion of recurrence
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5.4 HPV vaccination after conization
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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
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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:
|
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 |
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6.2.2 Treatment of pelvic wall recurrence after first-line or adjuvant radio-/radiochemotherapy
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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 |
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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 |
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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+ |
|
18.3. mod. 2021 |
Evidence-based recommendation Palliative drug therapy should be administered in the form of platinum-containing combination chemotherapy. |
B |
1+ |
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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+ |
|
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+ |
|
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+ |
|
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
#
#
#
#
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− |
|
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− |
#
#
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.
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]).


13.1.1 Center concept – interdisciplinary tumor board
#
13.1.2 Advanced training options
#
#
#
#


#
-
References/Literatur
- 1 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF). Supportive Therapie bei onkologischen PatientInnen – Langversion 1.3, 2020, AWMF Registernummer: 032/054OL. Online (Stand: 01.09.2021): https://www.leitlinienprogramm-onkologie.de/leitlinien/supportive-therapie/
- 2 Choi H, Palmer MH, Park J. Meta-analysis of pelvic floor muscle training: randomized controlled trials in incontinent women. Nurs Res 2007; 56: 226-234
- 3 Dumoulin C, Hay-Smith J. Pelvic floor muscle training versus no treatment, or inactive control treatments, for urinary incontinence in women. Cochrane Database Syst Rev 2010; (01) CD005654
- 4 Hosker G, Cody JD, Norton CC. Electrical stimulation for faecal incontinence in adults. Cochrane Database Syst Rev 2007; (03) CD001310
- 5 Imamura M, Abrams P, Bain C. et al. Systematic review and economic modelling of the effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence. Health Technol Assess 2010; 14: 1-188 iii–iv
- 6 Norton C, Cody JD. Biofeedback and/or sphincter exercises for the treatment of faecal incontinence in adults. Cochrane Database Syst Rev 2012; (07) CD002111
- 7 Shamliyan TA, Kane RL, Wyman J. et al. Systematic review: randomized, controlled trials of nonsurgical treatments for urinary incontinence in women. Ann Intern Med 2008; 148: 459-473
- 8 Theofrastous JP, Wyman JF, Bump RC. et al. Effects of pelvic floor muscle training on strength and predictors of response in the treatment of urinary incontinence. Neurourol Urodyn 2002; 21: 486-490
- 9 Velthuis MJ, Agasi-Idenburg SC, Aufdemkampe G. et al. The effect of physical exercise on cancer-related fatigue during cancer treatment: a meta-analysis of randomised controlled trials. Clin Oncol 2010; 22: 208-221
- 10 Cramp F, Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev 2008; (02) CD006145
- 11 Brown JC, Huedo-Medina TB, Pescatello LS. et al. Efficacy of exercise interventions in modulating cancer-related fatigue among adult cancer survivors: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2011; 20: 123-133
- 12 Khatcheressian JL, Wolff AC, Smith TJ. et al. American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol 2006; 24: 5091-5097
- 13 Grunfeld E, Dhesy-Thind S, Levine M. Clinical practice guidelines for the care and treatment of breast cancer: follow-up after treatment for breast cancer (summary of the 2005 update). CMAJ 2005; 172: 1319-1320
- 14 Pestalozzi BC, Luporsi-Gely E, Jost LM. et al. ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and follow-up of primary breast cancer. Ann Oncol 2005; 16 (Suppl. 01) i7-i9
- 15 Hurria A, Hudis C. Follow-up care of breast cancer survivors. Crit Rev Oncol Hematol 2003; 48: 89-99
- 16 Rojas MP, Telaro E, Russo A. et al. Follow-up strategies for women treated for early breast cancer. Cochrane Database Syst Rev 2005; (01) CD001768
- 17 Palli D, Russo A, Saieva C. et al. Intensive vs. clinical follow-up after treatment of primary breast cancer: 10-year update of a randomized trial. National Research Council Project on Breast Cancer Follow-up. JAMA 1999; 281: 1586
- 18 Gulliford T, Opomu M, Wilson E. et al. Popularity of less frequent follow up for breast cancer in randomised study: initial findings from the hotline study. BMJ 1997; 314: 174-177
- 19 van Nagell jr. JR, Rayburn W, Donaldson ES. et al. Therapeutic implications of patterns of recurrence in cancer of the uterine cervix. Cancer 1979; 44: 2354-2361
- 20 Guskova E, Kit OI, Nerodo GA. et al. Prognostic factors of cervical cancer recurrence. J Clin Oncol 2016; 34(15_suppl): e17025
- 21 Hong JH, Tsai CS, Lai CH. et al. Recurrent squamous cell carcinoma of cervix after definitive radiotherapy. Int J Radiat Oncol Biol Phys 2004; 60: 249-257
- 22 Kamura T, Tsukamoto N, Tsuruchi N. et al. Multivariate analysis of the histopathologic prognostic factors of cervical cancer in patients undergoing radical hysterectomy. Cancer 1992; 69: 181-186
- 23 Noh JM, Park W, Kim YS. et al. Comparison of clinical outcomes of adenocarcinoma and adenosquamous carcinoma in uterine cervical cancer patients receiving surgical resection followed by radiotherapy: a multicenter retrospective study (KROG 13-10). Gynecol Oncol 2014; 132: 618-623
- 24 Perez CA, Fox S, Lockett MA. et al. Impact of dose in outcome of irradiation alone in carcinoma of the uterine cervix: analysis of two different methods. Int J Radiat Oncol Biol Phys 1991; 21: 885-898
- 25 Scatchard K, Forrest JL, Flubacher M. et al. Chemotherapy for metastatic and recurrent cervical cancer. Cochrane Database Syst Rev 2012; (10) CD006469
- 26 Hirte HW, Strychowsky JE, Oliver T. et al. Chemotherapy for recurrent, metastatic, or persistent cervical cancer: a systematic review. Int J Gynecol Cancer 2007; 17: 1194-1204
- 27 Tzioras S, Pavlidis N, Paraskevaidis E. et al. Effects of different chemotherapy regimens on survival for advanced cervical cancer: systematic review and meta-analysis. Cancer Treat Rev 2007; 33: 24-38
- 28 Kitagawa R, Katsumata N, Shibata T. et al. Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Cisplatin in Metastatic or Recurrent Cervical Cancer: The Open-Label Randomized Phase III Trial JCOG0505. J Clin Oncol 2015; 33: 2129-2135
- 29 Lorusso D, Petrelli F, Coinu A. et al. A systematic review comparing cisplatin and carboplatin plus paclitaxel-based chemotherapy for recurrent or metastatic cervical cancer. Gynecol Oncol 2014; 133: 117-123
- 30 Long 3rd HJ, Bundy BN, Grendys jr. EC. et al. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol 2005; 23: 4626-4633
- 31 Tewari KS, Sill MW, Penson RT. et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet 2017; 390: 1654-1663
- 32 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF). Palliativmedizin für Patienten mit einer nicht-heilbaren Krebserkrankung, Langversion 2.1, 2020, AWMF-Registernummer: 128/001OL. Online (Stand: 01.04.2020): https://www.leitlinienprogramm-onkologie.de/leitlinien/palliativmedizin/
- 33 Haun MW, Estel S, Rucker G. et al. Early palliative care for adults with advanced cancer. Cochrane Database Syst Rev 2017; (06) CD011129
- 34 Adler K, Schlieper D, Kindgen-Milles D. et al. Integration of palliative care into intensive care: Systematic review. Anaesthesist 2017; 66: 660-666
- 35 Dalgaard KM, Bergenholtz H, Nielsen ME. et al. Early integration of palliative care in hospitals: A systematic review on methods, barriers, and outcome. Palliat Support Care 2014; 12: 495-513
- 36 Davis MP, Temel JS, Balboni T. et al. A review of the trials which examine early integration of outpatient and home palliative care for patients with serious illnesses. Ann Palliat Med 2015; 4: 99-121
- 37 Gaertner J, Siemens W, Meerpohl JJ. et al. Effect of specialist palliative care services on quality of life in adults with advanced incurable illness in hospital, hospice, or community settings: systematic review and meta-analysis. BMJ 2017; 357: j2925
- 38 Hui D, Kim YJ, Park JC. et al. Integration of oncology and palliative care: a systematic review. Oncologist 2015; 20: 77-83
- 39 Tassinari D, Drudi F, Monterubbianesi MC. et al. Early Palliative Care in Advanced Oncologic and Non-Oncologic Chronic Diseases: A Systematic Review of Literature. Rev Recent Clin Trials 2016; 11: 63-71
- 40 Hui D, Meng YC, Bruera S. et al. Referral Criteria for Outpatient Palliative Cancer Care: A Systematic Review. Oncologist 2016; 21: 895-901
- 41 Fertility preservation for patients with malignant disease. Guideline of the DGGG, DGU and DGRM (S2k-Level, AWMF Registry No. 015/082, November 2017). Online (Stand: 31.03.2020): http://www.awmf.org/leitlinien/detail/ll/015-082.html
- 42 De Vincenzo R, Tortorella L, Ricci C. et al. Locally advanced cervical cancer complicating pregnancy: A case of competing risks from the Catholic University of the Sacred Heart in Rome. Gynecol Oncol 2018; 150: 398-405
- 43 Fader AN, Alward EK, Niederhauser A. et al. Cervical dysplasia in pregnancy: a multi-institutional evaluation. Am J Obstet Gynecol 2010; 203: 113.e1-113.e6
- 44 Cohen JG, Kapp DS, Shin JY. et al. Small cell carcinoma of the cervix: treatment and survival outcomes of 188 patients. Am J Obstet Gynecol 2010; 203: 347.e1-347.e6
- 45 Lee SW, Nam JH, Kim DY. et al. Unfavorable prognosis of small cell neuroendocrine carcinoma of the uterine cervix: a retrospective matched case-control study. Int J Gynecol Cancer 2010; 20: 411-416
- 46 Tian WJ, Zhang MQ, Shui RH. Prognostic factors and treatment comparison in early-stage small cell carcinoma of the uterine cervix. Oncol Lett 2012; 3: 125-130
- 47 Moore DH, Blessing JA, McQuellon RP. et al. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol 2004; 22: 3113-3119
- 48 McCusker ME, Cote TR, Clegg LX. et al. Endocrine tumors of the uterine cervix: incidence, demographics, and survival with comparison to squamous cell carcinoma. Gynecol Oncol 2003; 88: 333-339
- 49 Chen J, Macdonald OK, Gaffney DK. Incidence, mortality, and prognostic factors of small cell carcinoma of the cervix. Obstet Gynecol 2008; 111: 1394-1402
- 50 Tempfer CB, Tischoff I, Dogan A. et al. Neuroendocrine carcinoma of the cervix: a systematic review of the literature. BMC Cancer 2018; 18: 530
- 51 Xu F, Ma J, Yi H. et al. Clinicopathological Aspects of Small Cell Neuroendocrine Carcinoma of the Uterine Cervix: a Multicenter Retrospective Study and Meta-Analysis. Cell Physiol Biochem 2018; 50: 1113-1122
Correspondebce/Korrespondenzadresse
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
-
References/Literatur
- 1 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF). Supportive Therapie bei onkologischen PatientInnen – Langversion 1.3, 2020, AWMF Registernummer: 032/054OL. Online (Stand: 01.09.2021): https://www.leitlinienprogramm-onkologie.de/leitlinien/supportive-therapie/
- 2 Choi H, Palmer MH, Park J. Meta-analysis of pelvic floor muscle training: randomized controlled trials in incontinent women. Nurs Res 2007; 56: 226-234
- 3 Dumoulin C, Hay-Smith J. Pelvic floor muscle training versus no treatment, or inactive control treatments, for urinary incontinence in women. Cochrane Database Syst Rev 2010; (01) CD005654
- 4 Hosker G, Cody JD, Norton CC. Electrical stimulation for faecal incontinence in adults. Cochrane Database Syst Rev 2007; (03) CD001310
- 5 Imamura M, Abrams P, Bain C. et al. Systematic review and economic modelling of the effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence. Health Technol Assess 2010; 14: 1-188 iii–iv
- 6 Norton C, Cody JD. Biofeedback and/or sphincter exercises for the treatment of faecal incontinence in adults. Cochrane Database Syst Rev 2012; (07) CD002111
- 7 Shamliyan TA, Kane RL, Wyman J. et al. Systematic review: randomized, controlled trials of nonsurgical treatments for urinary incontinence in women. Ann Intern Med 2008; 148: 459-473
- 8 Theofrastous JP, Wyman JF, Bump RC. et al. Effects of pelvic floor muscle training on strength and predictors of response in the treatment of urinary incontinence. Neurourol Urodyn 2002; 21: 486-490
- 9 Velthuis MJ, Agasi-Idenburg SC, Aufdemkampe G. et al. The effect of physical exercise on cancer-related fatigue during cancer treatment: a meta-analysis of randomised controlled trials. Clin Oncol 2010; 22: 208-221
- 10 Cramp F, Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev 2008; (02) CD006145
- 11 Brown JC, Huedo-Medina TB, Pescatello LS. et al. Efficacy of exercise interventions in modulating cancer-related fatigue among adult cancer survivors: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2011; 20: 123-133
- 12 Khatcheressian JL, Wolff AC, Smith TJ. et al. American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol 2006; 24: 5091-5097
- 13 Grunfeld E, Dhesy-Thind S, Levine M. Clinical practice guidelines for the care and treatment of breast cancer: follow-up after treatment for breast cancer (summary of the 2005 update). CMAJ 2005; 172: 1319-1320
- 14 Pestalozzi BC, Luporsi-Gely E, Jost LM. et al. ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and follow-up of primary breast cancer. Ann Oncol 2005; 16 (Suppl. 01) i7-i9
- 15 Hurria A, Hudis C. Follow-up care of breast cancer survivors. Crit Rev Oncol Hematol 2003; 48: 89-99
- 16 Rojas MP, Telaro E, Russo A. et al. Follow-up strategies for women treated for early breast cancer. Cochrane Database Syst Rev 2005; (01) CD001768
- 17 Palli D, Russo A, Saieva C. et al. Intensive vs. clinical follow-up after treatment of primary breast cancer: 10-year update of a randomized trial. National Research Council Project on Breast Cancer Follow-up. JAMA 1999; 281: 1586
- 18 Gulliford T, Opomu M, Wilson E. et al. Popularity of less frequent follow up for breast cancer in randomised study: initial findings from the hotline study. BMJ 1997; 314: 174-177
- 19 van Nagell jr. JR, Rayburn W, Donaldson ES. et al. Therapeutic implications of patterns of recurrence in cancer of the uterine cervix. Cancer 1979; 44: 2354-2361
- 20 Guskova E, Kit OI, Nerodo GA. et al. Prognostic factors of cervical cancer recurrence. J Clin Oncol 2016; 34(15_suppl): e17025
- 21 Hong JH, Tsai CS, Lai CH. et al. Recurrent squamous cell carcinoma of cervix after definitive radiotherapy. Int J Radiat Oncol Biol Phys 2004; 60: 249-257
- 22 Kamura T, Tsukamoto N, Tsuruchi N. et al. Multivariate analysis of the histopathologic prognostic factors of cervical cancer in patients undergoing radical hysterectomy. Cancer 1992; 69: 181-186
- 23 Noh JM, Park W, Kim YS. et al. Comparison of clinical outcomes of adenocarcinoma and adenosquamous carcinoma in uterine cervical cancer patients receiving surgical resection followed by radiotherapy: a multicenter retrospective study (KROG 13-10). Gynecol Oncol 2014; 132: 618-623
- 24 Perez CA, Fox S, Lockett MA. et al. Impact of dose in outcome of irradiation alone in carcinoma of the uterine cervix: analysis of two different methods. Int J Radiat Oncol Biol Phys 1991; 21: 885-898
- 25 Scatchard K, Forrest JL, Flubacher M. et al. Chemotherapy for metastatic and recurrent cervical cancer. Cochrane Database Syst Rev 2012; (10) CD006469
- 26 Hirte HW, Strychowsky JE, Oliver T. et al. Chemotherapy for recurrent, metastatic, or persistent cervical cancer: a systematic review. Int J Gynecol Cancer 2007; 17: 1194-1204
- 27 Tzioras S, Pavlidis N, Paraskevaidis E. et al. Effects of different chemotherapy regimens on survival for advanced cervical cancer: systematic review and meta-analysis. Cancer Treat Rev 2007; 33: 24-38
- 28 Kitagawa R, Katsumata N, Shibata T. et al. Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Cisplatin in Metastatic or Recurrent Cervical Cancer: The Open-Label Randomized Phase III Trial JCOG0505. J Clin Oncol 2015; 33: 2129-2135
- 29 Lorusso D, Petrelli F, Coinu A. et al. A systematic review comparing cisplatin and carboplatin plus paclitaxel-based chemotherapy for recurrent or metastatic cervical cancer. Gynecol Oncol 2014; 133: 117-123
- 30 Long 3rd HJ, Bundy BN, Grendys jr. EC. et al. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol 2005; 23: 4626-4633
- 31 Tewari KS, Sill MW, Penson RT. et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet 2017; 390: 1654-1663
- 32 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF). Palliativmedizin für Patienten mit einer nicht-heilbaren Krebserkrankung, Langversion 2.1, 2020, AWMF-Registernummer: 128/001OL. Online (Stand: 01.04.2020): https://www.leitlinienprogramm-onkologie.de/leitlinien/palliativmedizin/
- 33 Haun MW, Estel S, Rucker G. et al. Early palliative care for adults with advanced cancer. Cochrane Database Syst Rev 2017; (06) CD011129
- 34 Adler K, Schlieper D, Kindgen-Milles D. et al. Integration of palliative care into intensive care: Systematic review. Anaesthesist 2017; 66: 660-666
- 35 Dalgaard KM, Bergenholtz H, Nielsen ME. et al. Early integration of palliative care in hospitals: A systematic review on methods, barriers, and outcome. Palliat Support Care 2014; 12: 495-513
- 36 Davis MP, Temel JS, Balboni T. et al. A review of the trials which examine early integration of outpatient and home palliative care for patients with serious illnesses. Ann Palliat Med 2015; 4: 99-121
- 37 Gaertner J, Siemens W, Meerpohl JJ. et al. Effect of specialist palliative care services on quality of life in adults with advanced incurable illness in hospital, hospice, or community settings: systematic review and meta-analysis. BMJ 2017; 357: j2925
- 38 Hui D, Kim YJ, Park JC. et al. Integration of oncology and palliative care: a systematic review. Oncologist 2015; 20: 77-83
- 39 Tassinari D, Drudi F, Monterubbianesi MC. et al. Early Palliative Care in Advanced Oncologic and Non-Oncologic Chronic Diseases: A Systematic Review of Literature. Rev Recent Clin Trials 2016; 11: 63-71
- 40 Hui D, Meng YC, Bruera S. et al. Referral Criteria for Outpatient Palliative Cancer Care: A Systematic Review. Oncologist 2016; 21: 895-901
- 41 Fertility preservation for patients with malignant disease. Guideline of the DGGG, DGU and DGRM (S2k-Level, AWMF Registry No. 015/082, November 2017). Online (Stand: 31.03.2020): http://www.awmf.org/leitlinien/detail/ll/015-082.html
- 42 De Vincenzo R, Tortorella L, Ricci C. et al. Locally advanced cervical cancer complicating pregnancy: A case of competing risks from the Catholic University of the Sacred Heart in Rome. Gynecol Oncol 2018; 150: 398-405
- 43 Fader AN, Alward EK, Niederhauser A. et al. Cervical dysplasia in pregnancy: a multi-institutional evaluation. Am J Obstet Gynecol 2010; 203: 113.e1-113.e6
- 44 Cohen JG, Kapp DS, Shin JY. et al. Small cell carcinoma of the cervix: treatment and survival outcomes of 188 patients. Am J Obstet Gynecol 2010; 203: 347.e1-347.e6
- 45 Lee SW, Nam JH, Kim DY. et al. Unfavorable prognosis of small cell neuroendocrine carcinoma of the uterine cervix: a retrospective matched case-control study. Int J Gynecol Cancer 2010; 20: 411-416
- 46 Tian WJ, Zhang MQ, Shui RH. Prognostic factors and treatment comparison in early-stage small cell carcinoma of the uterine cervix. Oncol Lett 2012; 3: 125-130
- 47 Moore DH, Blessing JA, McQuellon RP. et al. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol 2004; 22: 3113-3119
- 48 McCusker ME, Cote TR, Clegg LX. et al. Endocrine tumors of the uterine cervix: incidence, demographics, and survival with comparison to squamous cell carcinoma. Gynecol Oncol 2003; 88: 333-339
- 49 Chen J, Macdonald OK, Gaffney DK. Incidence, mortality, and prognostic factors of small cell carcinoma of the cervix. Obstet Gynecol 2008; 111: 1394-1402
- 50 Tempfer CB, Tischoff I, Dogan A. et al. Neuroendocrine carcinoma of the cervix: a systematic review of the literature. BMC Cancer 2018; 18: 530
- 51 Xu F, Ma J, Yi H. et al. Clinicopathological Aspects of Small Cell Neuroendocrine Carcinoma of the Uterine Cervix: a Multicenter Retrospective Study and Meta-Analysis. Cell Physiol Biochem 2018; 50: 1113-1122







