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.
Key words: guideline, cervical cancer, cervical intraepithelial neoplasia, therapy, follow-up
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).
Guidelines program of the DGGG, OEGGG and SGGG
For more information, please refer to the end of this guideline.
Guideline funding
This guideline was funded by German Cancer Aid ( Deutsche Krebshilfe , DKH) as part of the German Guideline Program in Oncology.
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
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/
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 |
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
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.
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.
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.
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.
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.
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/ ).
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 |
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 .
2 Psycho-oncology and Quality of Life
2.1 Psycho-oncological support
2.2 Measuring quality of life
3 Integrative Medicine
3.1 Counselling about complementary and alternative medicine (CAM)
3.2 Importance of alternative medicine
4 Rehabilitation
4.1 Physiotherapy treatment during rehabilitation
4.2 Treatment of lymphedema during rehabilitation
4.3 Treatment of fatigue syndrome during rehabilitation
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 .
5.1 Follow-up without suspicion of recurrence
5.2 Tumor markers
5.3 Expanded diagnostic workup for suspicion of recurrence
5.4 HPV vaccination after conization
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
6.2 Treatment of local recurrence
6.2.1 Treatment of central tumor recurrence after first-line surgical treatment
6.2.2 Treatment of pelvic wall recurrence after first-line or adjuvant radio-/radiochemotherapy
6.2.3 Palliative treatment of local recurrence (when margin-negative surgery is not possible)
7 Distant Metastasis
7.1 Therapy options for distant metastasis
7.1.1 Isolated metastasis
7.1.2 Disseminated metastases
7.1.3 Systemic therapies in the metastatic setting
7.1.3.1 Targeted therapy
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.
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 .
11 Incidental Cervical Cancer After Simple Hysterectomy
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
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 ).
Abb. 1.
Agreed care algorithm (reviewed in 2021). [rerif]
13.1.1 Center concept – interdisciplinary tumor board
13.1.2 Advanced training options
Footnotes
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.
| 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 | ||
| 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 | ||
| 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 | ||
| 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 | ||
| 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 | ||
| 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 | ||
| 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 | ||
| 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 | ||
| 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 | ||
| 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 | ||
| 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 | ||
| 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 | ||
| 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 | ||
| 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 | ||
| 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 | ||
| 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 | ||
| 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 | ||
| 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 | ||
| 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 |
| 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 |
| 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 |
| 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 | ||
| 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 |
| 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 | ||
| 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 |
| 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 | ||
| 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 | ||
| 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 | ||
| 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 | ||
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