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 1 with Recommendations on Epidemiology, Screening, Diagnostics and Therapy

Abstract

Aim This update of the interdisciplinary S3 guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL) was published in March 2021. This 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 of updating the S3 guideline dating from 2014 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 a 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 took account of more recently published literature and the appraisal of the new evidence.

Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, screening, diagnostic workup and therapy of patients with cervical cancer. The most important new aspects included in this updated guideline include the newly published FIGO classification of 2018, the radical open surgery approach for cervical cancers up to FIGO stage IB1, and 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.

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 1 with Recommendations on Epidemiology, Screening, Diagnostics and Therapy. Geburtsh Frauenheilk 2022; 82: 139 – 180

Guideline documents

The complete long version, a version for patients and a slide version of this guideline, all of them in German, 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 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 the German Health Insurance Funds (MDK-Gemeinschaft) were involved in 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  Lead 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 (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 Leading 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)

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

Tab. 3  Methodological supervision.

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 Medical Knowledge Management)	Berlin
PD Dr. Simone Wesselmann, MBA (German Cancer Society – certification, quality indicators)	Berlin
Biologist Gregor Wenzel	Berlin

Tab. 4  Guidelines Office and project team.

Name	City
Dr. Martin C. Koch (Guidelines Office)	Erlangen
Dr. Frederik A. Stübs (Guidelines 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 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 that the current therapies administered to patients with cervical cancer can vary greatly. The aim of this updated guideline remains the same as that of the previous version of 2014. This guideline on 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 the 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 guideline has an intersectoral scope. It covers both outpatient and in-patient care as well as rehabilitation.

Target user groups

This S3 guideline addresses 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 representing 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, 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 when compiling this guideline is described in the guideline report. The guideline report 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) shown 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

In this guideline, the level of evidence (using the SIGN classification) in the underlying studies and, when making recommendations, the strength of the recommendation (grade of recommendation) is given for all evidence-based statements and recommendations. As regards the strength of recommendations, the guideline differentiates between three grades of recommendation ( Table 6 ), and the level of recommendation is reflected in the wording used in the respective recommendation:

Tab. 6  Grade of recommendation.

Symbol	Description of level of obligation to comply with the recommendation	Term
A	Strong recommendation	must/must not
B	Simple recommendation	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 (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: Although studies with results which point in a specific direction are available, 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 offered without restrictions. 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 it is not available in regional healthcare systems for structural reasons.

Statements

Statements are expositions or explanations of specific facts, circumstances or problems without directly calling to action. They are adopted using the same approach used for recommendations and following a formal consensus procedure, and they may be based either on study results or on expert opinions.

Achieving consensus and level of consensus

At structured NIH-type (S2k/S3 level) consensus conferences, authorized participants attending the conference voted on draft statements and recommendations. Conferences are structured as follows: a recommendation is presented; participants can ask 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  Epidemiology

Data from the Robert Koch Institute and the GEKID from 2019 show that in 2016, 4380 women developed cervical cancer and 1562 women died from cervical cancer in Germany. Compared to the figures for 2002, the incidence of cervical cancer (6500 vs. 4380) has declined significantly although the number of deaths (1700 vs. 1562) from cervical cancer has decreased only slightly. It is expected that the general administration of HPV vaccinations to girls between the ages of 9 and 14 years in 2007 will reduce future incidence and mortality rates even more. Since June 2018, the STIKO has also recommended that boys between the ages of 9 to 14 years be vaccinated. The herd protection obtained by vaccinating a sufficient number of people should further reduce the incidence and mortality of cervical cancer. In 2016, the relative 5-year survival rate for cervical cancer was 67% and the 10-year survival rate was 63% 1 ,  2 . The age distribution showed a peak between the ages of 40 and 59 years. The mean age at first diagnosis of cervical cancer is currently 55 years and has dropped by 15 years in the last 25 years 1 . Further information on regional differences, histological subtypes and risk factors are available in the long (English-language) version of the guideline.

2  Prevention and Screening

Because complementary S3 guidelines are already available, this guideline did not develop its own recommendations on prevention and screening. Interested parties should refer to the relevant S3 guidelines “Vaccination for the Prevention of HPV-associated Neoplasia (AWMF Registry No. 082/002)” and “Prevention of Cervical Cancer (AWMF Registry No. 015/027OL)” 3 ,  4 .

3  Patient Information

3.1  Informing patients and substance of the information

3.1.1  Informing the patient of the diagnosis

3.1.2  Informing the patient about treatment options

3.1.2.1  Information provided to patients with metastatic or recurrent cervical cancer

4  Diagnosis

The new FIGO classification was introduced in 2018. This new classification now also incorporates findings obtained with radiographic imaging or biopsies to determine the stage of disease (s. Table 19 on p. 261 of the long version of the S3 guideline). In addition, paraaortic lymph nodes are now classified as pN1 and no longer as pM1. Previously, the FIGO classification of cervical cancer consisted of purely clinical staging based on bimanual examination of the patient by a gynecologist. Because the (new) FIGO classification is not congruent with that of the (old) TNM, the old FIGO version is still used in this updated version of the guideline. There are currently no data from clinical studies using the new classification.

4.1  Diagnostic workup as the basis for therapeutic decisions

4.1.1  Images agreed upon by the guideline authors on the diagnostic workup and staging as the basis for therapeutic decisions

The guideline authors agreed on two graphs outlining the diagnostic workup and staging of lesions, as this affects the therapeutic decisions regarding lesions classified as FIGO ≤ IIB or > IIB ( Figs. 1 and 2 ).

Abb. 1.

 Diagnostic workup and staging as the basis for therapeutic decision for lesions which are ≤ FIGO stage IIB (reviewed in 2021). [rerif]

Abb. 2.

 Diagnostic workup and staging as the basis for therapeutic decision for lesions which are > FIGO stage IIB (reviewed in 2021). [rerif]

4.1.2  Recommendations for the diagnostic workup

5  Pathology

5.1  Classification of invasive cervical cancers

5.1.1  Tumor typing

The majority of invasive cervical cancers are squamous cell carcinomas (~ 80%) and adenocarcinomas (~ 5 – 20%) 15 . Other tumor entities are rare. Neuroendocrine (large or small cell) carcinoma and non-HPV-associated adenocarcinoma with the exception of clear cell adenocarcinoma are tumor types which have a particularly unfavorable prognosis.

5.1.2  Staging of cervical cancer

Postoperative staging is based on the TNM classification 16 . Lesions are differentiated into micro- and macroinvasive cancers.

5.2  Tissue preparation

5.2.1  Diagnostic biopsies

5.2.2  Conization

5.2.3  Trachelectomy

5.2.4  Specimens after radical hysterectomy

5.2.5  Lymphadenectomy specimens

5.2.6  Sentinel lymph nodes

5.3  Morphological prognostic factors

Established prognostic factors for cervical cancer are tumor stage and evidence of pelvic or paraaortic lymph node metastasis 17  –  23 . For more information on resection margins, tumor size, tumor-type histology, HPV status, IECC classification, venous infiltration, perineural sheath infiltration, depth of infiltration, micro- and macrometastasis, immunohistochemical ultrastaging, molecular markers, TCGA classification, mutation load and PD-L1 expression, see Chapter 7.3 of the long version of the guideline.

6  Basic Principles of Therapy

When this guideline was being updated, the new FIGO classification was already available to the guideline group. The underlying data is based on the previous classification. Therefore, all tumor stages refer to the old FIGO classification.

6.1  Primary therapy

Primary therapy consists of either surgery or radiochemotherapy. Surgical therapy is recommended for patients with FIGO stage IIA disease or lower. Primary radio(chemo)therapy is predominantly used to treat later stages of disease with more extensive infiltration (from stage IIB), disease with lymph node involvement or inoperable disease. Radio(chemo)therapy is also recommended when several preoperatively determined risk factors are present (i.e., lymphangitis [L1], R1, G3 [its importance is dubious and only in combination with two additional risk factors], neuroendocrine carcinoma, tumor > 4 cm [stage], or histology positive for lymph node metastasis). The choice of treatment for stage IV disease should be made on an individual basis. In general, when deciding on the appropriate therapy, no differences are made between the different histological tumor entities (e.g., adenocarcinoma or squamous cell carcinoma). Although the diagnosis of stage IB and II disease is different prior to therapy, surgery and simultaneous radio(chemo)therapy have equivalent long-term outcomes despite the differences in patterns of recurrence and the side-effects profiles of the therapies.

6.1.1  Surgery – hysterectomy and lymphadenectomy

6.1.1.1  Uterine surgery

Different surgical techniques and principles can be used for cervical and uterine surgery (conization, simple or radical trachelectomy, simple or radical hysterectomy) ( Fig. 3 ). The Piver-Rutledge classification dating from 1974 is the standard classification to rank radical hysterectomies 24 .

Abb. 3.

 Surgical therapy techniques and principles (reviewed 2021). [rerif]

6.1.1.2  Lymphadenectomy or resection of sentinel lymph nodes to identify tumor stages

In this updated guideline, the use of sentinel lymph nodes as a surgical staging concept for tumors ≤ 2 cm and for pT1a1 and L1 disease was based on new data. It has also been shown that patent blue and radioactive marking are equivalent to intraoperative marking with indocyanine green (ICG).

6.1.1.3  Drainage placement after lymphadenectomy

6.1.2  Radio(chemo)therapy

Radio(chemo)therapy may be administered as neoadjuvant, primary or adjuvant therapy. Standard radio(chemo)therapy is carried out using cisplatin as a radiosensitizer. It is important to differentiate between percutaneous radiotherapy and brachytherapy. Which areas (pelvic/paraaortic) are selected for irradiation depends on histological verification of lymph node involvement and not on any imaging-based presumption of affected lymph nodes. Standard radio(chemo)therapy for stage IIb disease and above as well as lower stages of disease with histologically verified risk factors consists of primary, initially percutaneous, irradiation of the primary tumor and pelvic lymph nodes combined with cisplatin-based chemotherapy followed by brachytherapy.

6.3  Adjuvant therapy

6.3.1  Adjuvant therapy after primary surgery

6.3.2  Adjuvant therapy after primary radiochemotherapy

After primary radio(chemo)therapy has been carried out, the option to perform secondary hysterectomy or expanded chemotherapy may be discussed in specific situations (see Statement).

6.5  Stage-dependent therapy

6.5.1  Standard therapy for invasive cervical cancer

6.5.1.1  FIGO stage IA (synonyms: early stromal invasion, microcarcinoma or microinvasive carcinoma)

6.5.1.2  FIGO stage IB1 and IIA1

6.5.1.3  FIGO stage IB2, IIA2 and IIB

6.5.1.4  FIGO stage III

6.5.1.5  FIGO stage IV

7  Surgical Treatment

Based on new evidence from the LACC trial, the recommendation for the surgical approach to be used for radical hysterectomy in patients with cervical cancer was changed 31 . A clear preference was given to open procedures as opposed to laparoscopic approaches. The relevant recommendation was revised. The guideline authors rated prophylactic salpingectomy carried out in combination with planned hysterectomy as positive. The importance of secondary hysterectomy after radiochemotherapy is still not clear.

8  Radiotherapy

After some revision, the recommendations for primary radiochemotherapy including external radiotherapy, simultaneous cisplatin-based chemotherapy and brachytherapy were confirmed. The grading of recommendations on the use of intensity-modulated radiotherapy techniques and for MRI-guided treatment planning for brachytherapy in the context of primary radiochemotherapy was increased as new data is now available which shows the clinical benefits of these techniques.

8.1  Radiochemotherapy

8.1.1  Radiotherapy techniques (percutaneous radiotherapy)

8.1.2  Brachytherapy technique in primary combined radiochemotherapy

8.1.3  Indications for primary radiotherapy or radio(chemo)therapy

8.1.4  Adjuvant radio(chemo)therapy

8.1.5  Adjuvant chemotherapy after completing radio(chemo)therapy

8.1.6  Neoadjuvant radio(chemo)therapy

8.1.7  Ovarian preservation and fertility

8.1.8  Anemia during radiochemotherapy

8.1.9  Hyperthermia to treat cervical cancer

No.	Recommendations/Statements	GoR	LoE	Sources
4.1. reviewed 2021	Consensus-based statement Recommendations on the prevention and early detection of cervical carcinoma are presented in the Level 3 guidelines (S3) “Vaccine Prevention of HPV-Associated Neoplasia” (AWMF register no. 082/002) and “Prevention of Cervical Carcinoma” (AWMF register no. 015/027OL).	EC

No.	Recommendations/Statements	GoR	LoE	Sources
5.1. reviewed 2021	Consensus-based recommendation High-quality and pertinent information materials (using print or Internet media) must be produced in accordance with defined quality criteria for health information and made available to patients, to support them in independent decision-making for or against medical measures by providing generally comprehensible risk information (e.g., with details of absolute risk reductions).	EC

No.	Recommendations/Statements	GoR	LoE	Sources
5.2. reviewed 2021	Consensus-based recommendation The patient must be informed that her partner or a relative can be invited to be included in the discussion(s).	EC
5.3. reviewed 2021	Consensus-based recommendation During the medical discussion, the patientʼs individual preferences, needs, worries and anxieties must be identified and taken into account. If a patient needs several discussions for the purpose, an offer of further discussions must be available.	EC
5.4. modified 2021	Consensus-based recommendation Providing the patient with medical information is primarily a task for the attending physician, but for specific topics it should be provided by other professional groups such as nurses, psycho-oncologists, etc.	EC
5.5. modified 2021	Consensus-based recommendation Information must be communicated and provided to the patient as early as possible on the basis of the following basic principles of patient-centered communication allowing participatory decision-making: Expressing empathy and active listening Direct, empathetic raising of difficult topics Avoiding specialist medical vocabulary, with specialist terms being explained if needed Using strategies for improving comprehension (repetition, summing up important information, using diagrams, etc.) Encouraging the patient to ask questions Permitting and encouraging expressions of emotion Offering further assistance	EC
5.6. reviewed 2021	Consensus-based recommendation The patient should be offered psychosocial and psycho-oncological support for psychological, sexual, and relationship problems.	EC
5.7. reviewed 2021	Consensus-based recommendation The patient must be informed about the option of contacting self-help groups.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
5.8. reviewed 2021	Consensus-based recommendation In accordance with the “Law on Improving Patientsʼ Rights,” the patient must be informed about all of the treatment options described in this guideline that are relevant to her and about their prospects of success and possible effects. In particular, effects on her physical appearance, sexual life, urinary and rectal continence, and aspects of female identity (self-image, fertility) should be mentioned.	EC
5.9. reviewed 2021	Consensus-based statement Principles, intended treatment goals, duration and implementation of the individual treatment measures Surgical treatment measures: Conization; trachelectomy Surgical staging and associated additional measures Forms of lymphadenectomy Forms of radical hysterectomy Exenteration procedures Surgical options in case of recurrence Radiotherapy: Primary radiotherapy/radio(chemo)therapy Secondary radiotherapy/radio(chemo)therapy Systemic therapy: Neoadjuvant/adjuvant chemotherapy Combined radio(chemo)therapy Targeted therapy Side effects of treatment and ways of treating them Late sequelae of the disease and therapy and ways of treating them Complementary therapy: Mention of the availability of complementary medicine to reduce side effects Participation in clinical studies: Principles and intended treatment goals Duration and implementation of therapy Effects and side effects currently known Special aspects (monitoring, additional measures, compliance, data storage and processing) Other information: Psycho-oncological support and services provided by self-help groups Options for rehabilitation Necessity of follow-up care Aspects of patientʼs own responsibility and compliance (e.g., providing information about symptoms and problems, treatment compliance)	EC
5.10. reviewed 2021	Consensus-based recommendation The patient must be informed about the patient guideline on diagnosis, treatment, and follow-up for patients with cervical carcinoma.	EC
5.11. reviewed 2021	Consensus-based statement Cervical carcinoma is not an emergency case. The patient can and must be given sufficient time for her own decision-making processes.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
5.12. reviewed 2021	Consensus-based recommendation The following points can be mentioned as forming the content of a discussion in the palliative situation: Aims of palliative medical therapy (alleviating suffering, treatment of pain – foremost goal: the patientʼs quality of life) Patientʼs anxieties and fears, with inclusion of her partner and relatives Radio(chemo)therapy – duration and intended effect Palliative drug treatment Palliative surgical treatment Individual treatment decisions, depending on the patientʼs personal life plans If the effectiveness of a treatment is limited, the result of the decision-making process may be to deliberately refrain from palliative tumor treatment Mention of different aspects of palliative care (rehabilitation, psychosocial medicine, psycho-oncology) Side effects and interactions of drugs and complementary medicine Involvement of local hospice group if appropriate Consultation with physicians and nursing services specializing in palliative medicine Problem situations arising during the course of disease: Pain Ureteral stenosis leading to renal failure Fistulas Fetid discharge Bleeding Paralytic or mechanical ileus Thrombosis, pulmonary embolism Symptomatic and supportive therapy: Treatment for lymphedema in the lower extremities Pain therapy Dysuria/bladder spasm Psychosocial and religious/spiritual assistance for the patient and her relatives Resources for assistance	EC

No.	Recommendations/Statements	GoR	LoE	Sources
6.1. modified 2021	Consensus-based recommendation Vaginal ultrasonography must be used for clinical imaging to establish the extent of local tumor spread, and renal ultrasonography to exclude urinary transport disturbance.	EC
6.2. modified 2021	Evidence-based recommendation Patients with histologically confirmed cervical carcinoma from FIGO stage IB2 to III inclusive should undergo pelvic MRI for assessment of locoregional tumor spread. Patients who are unable to undergo pelvic MRI for technical reasons should have a pelvic CT.	B	1+	5  –  7
6.3. modified 2021	Consensus-based recommendation Starting from FIGO IB2 to III, patients in whom pelvic MRI cannot be carried out for technical reasons should undergo locoregional imaging of the pelvis for staging purposes during staging CT examinations of the chest, abdomen, and pelvis.	EC
6.4. new 2021	Consensus-based recommendation Patients in FIGO stage IVA who are unable to undergo pelvic MRI for technical reasons should receive locoregional imaging staging of the pelvis as part of staging CT of the chest/abdomen/pelvis.	EC
6.5. modified 2021	Consensus-based recommendation Patients with histologically confirmed cervical carcinoma FIGO stage IB2 or above should undergo chest/abdominal/pelvic CT for assessment of tumor spread.	EC
6.6. reviewed 2021	Consensus-based recommendation If a tumor of the vaginal part of the cervix cannot be clearly assessed macroscopically, a differential colposcopy and targeted biopsy must be carried out.	EC
6.7. reviewed 2021	Consensus-based recommendation The histologically confirmed tumor stage should be the basis for interdisciplinary treatment decision-making at the tumor conference.	EC
6.8. modified 2021	Evidence-based recommendation PET-CT should not be used for treatment planning in primary cervical carcinoma.	B	2+	6 ,  8  –  11
6.9. modified 2021	Evidence-based recommendation When a local procedure (radiochemotherapy or exenteration) is being considered for treatment of a recurrence, PET-CT should be carried out to exclude lymph-node metastases and distant metastases.	B	2+	6 ,  12  –  14

No.	Recommendations/Statements	GoR	LoE	Sources
7.1. reviewed 2021	Consensus-based recommendation Tumor classification must be carried out on the basis of the currently valid edition of the WHO classification.	EC
7.2. reviewed 2021	Consensus-based recommendation In cervical carcinomas with neuroendocrine components, the latter must be reported along with the percentage of the total tumor that they represent.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
7.3. modified 2021	Consensus-based recommendation Staging must be carried out in accordance with the current edition of the TNM classification.	EC
7.4. reviewed 2021	Consensus-based recommendation A diagnosis of microinvasive cervical carcinoma must be based on the definitions given in the current editions of both the WHO and TNM classifications.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
7.5. reviewed 2021	Consensus-based recommendation The biopsy sample that has been taken must be processed in step sections.	EC
7.6. modified 2021	Consensus-based recommendation The report on the findings should mention the evidence and the grade of CIN, ACIS (and its variants in the form of stratified mucin-producing intraepithelial lesions [SMILE]), virus-associated changes, and possible invasion.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
7.7. reviewed 2021	Consensus-based recommendation The pathology report must state the size and characteristics of the excised (conization) specimen. The conization specimen must be completely processed and step sections must be prepared from each paraffin block.	EC
7.8. modified 2021	Consensus-based recommendation The histological report must note the type of lesion (CIN, ACIS and its variants in the form of stratified mucin-producing intraepithelial lesions [SMILE]), its location (endocervical, ectocervical), and its extent, as well as the presence of invasive tumor. When there is evidence of invasion, details must also be given of its extent and of lymphatic, vascular and perineural sheath invasion, as well as grading. The status of the resection margins must also be noted.	EC
7.9. new 2021	Consensus-based recommendation A multifocal microinvasive carcinoma is defined as evidence of invasive foci that are histologically clearly separate from each other at a minimum distance of 0.2 cm. The size of each invasive tumor focus must be reported separately, with the largest single lesion being relevant for staging.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
7.10. reviewed 2021	Consensus-based recommendation Morphological processing must take place in such a way that all therapeutically and prognostically relevant parameters can be assessed. The report must be produced on the basis of the currently valid WHO classification for tumor type and the current TNM classification for staging, as well as the R classification (UICC).	EC
7.11. modified 2021	Consensus-based recommendation The trachelectomy report must include the following details: Histological type (WHO) Grading Presence/absence of lymphatic or venous invasion (L and V status) Presence/absence of perineural sheath infiltration (Pn status) Staging (TNM) Depth of invasion and extent in millimeters in pT1a1 and pT1a2 Three-dimensional tumor size in centimeters (from pT1b1) Minimum distance from the resection margins (endocervical stroma in pT1b tumors) R classification (UICC)	EC

No.	Recommendations/Statements	GoR	LoE	Sources
7.12. reviewed 2021	Consensus-based recommendation Morphological processing must take place in such a way that all therapeutically and prognostically relevant parameters can be assessed. The report must be produced on the basis of the currently valid WHO classification for tumor type and the current TNM classification for staging, as well as the R classification (UICC).	EC
7.13. new 2021	Consensus-based recommendation To document intratumoral heterogeneity, macroscopically visible tumors ≤ 2 cm in size should be completely processed and at least one block per centimeter at the greatest tumor extension should be embedded from tumors larger than 2 cm.	EC
7.14. reviewed 2021	Consensus-based statement Deep stromal infiltration is defined as invasion by the cervical carcinoma into the outer third of the cervical stroma (> 66%).	EC
7.15. modified 2021	Consensus-based recommendation The radical hysterectomy report must include the following details: WHO histological type Grading Presence/absence of lymphatic or venous invasion (L and V status) Presence/absence of perineural sheath infiltration (Pn status) Staging (TNM), taking the conization findings into account in patients who have undergone conization Depth of invasion and extension in millimeters in pT1a1 and pT1a2 Depth of invasion relative to the cervical wall thickness (measurement or percentage figure) Three-dimensional tumor size in centimeters (from pT1b1) Minimum distance from the resection margins (endocervical stroma in pT1b tumors, vagina in pT2a tumors, and parametrium in pT2b tumors) R classification (UICC)	EC

No.	Recommendations/Statements	GoR	LoE	Sources
7.16. reviewed 2021	Consensus-based recommendation Micrometastases are defined as histological evidence of tumor cells in lymph nodes measuring ≥ 0.2 mm, but no larger than 0.2 cm.	EC
7.17. reviewed 2021	Consensus-based recommendation In lymphadenectomy specimens obtained during surgical treatment for cervical carcinoma, all removed lymph nodes must be histologically examined.	EC
7.18. reviewed 2021	Consensus-based recommendation Lymph nodes up to approx. 0.3 cm in size should be completely paraffin-embedded, and larger lymph nodes should be halved along the long axis and also completely paraffin-embedded.	EC
7.19. new 2021	Consensus-based recommendation Evidence of isolated tumor cells or micrometastases should be mentioned in the histological report and included in the TNM classification.	EC
7.20. reviewed 2021	Consensus-based recommendation The report on lymph nodes must include the following details: number of affected lymph nodes relative to the number of lymph nodes removed, correlated with the location of removal (pelvic/para-aortic).	EC

No.	Recommendations/Statements	GoR	LoE	Sources
7.21. reviewed 2021	Consensus-based recommendation Sentinel lymph nodes in cervical carcinoma must be completely paraffin-embedded and examined in step sections.	EC
7.22. new 2021	Consensus-based recommendation Sentinel lymph nodes in cervical carcinoma should be processed as follows: Lamellation of the adipose tissue that has been received, with identification of all sentinel lymph nodes Complete removal of all lymph nodes Halving of all lymph nodes ≤ 0.3 cm in size Lamellation of all lymph nodes > 0.3 cm into 0.2-cm thick lamellae Preparation of step sections Immunohistochemical ultrastaging With sentinel lymph nodes that cannot be identified macroscopically, complete embedding of the adipose tissue	EC
7.23. new 2021	Consensus-based recommendation Intraoperative rapid frozen-section examination (when clinically indicated) of sentinel lymph nodes in cervical carcinoma should be performed as follows: Standard work-up of the sentinel lymph nodes Examination of ALL sentinel lymph nodes in quick section If there is a macroscopically visible tumor, intraoperative examination of a sample of the involved lymph node is sufficient Macroscopically unremarkable lymph nodes must be examined completely intraoperatively Step sections (three) should be made from the frozen blocks The histological frozen-section examination can be supplemented with intraoperative imprint cytology	EC

No.	Recommendations/Statements	GoR	LoE	Sources
8.1. reviewed 2021	Consensus-based recommendation The aim of treatment for primary cervical carcinoma should be individualized therapy. The choice of treatment should take the following factors into account: Patientʼs general condition (with high levels of comorbidity) Patientʼs life situation Clinically/histologically defined stage of the disease Menopausal status Potential wish to have children Short-term and long-term sequelae of the various treatment options Any risk factors Overtreatment and undertreatment should be avoided.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
8.2. reviewed 2021	Consensus-based recommendation Treatment must be administered relative to the histological tumor stage, verified using surgical staging or interventional diagnosis.	EC
8.3. modified 2021	Consensus-based statement Sentinel lymphadenectomy alone should be used: For preoperative imaging (patent blue and radioactive) Or intraoperative imaging (indocyanine green) When sentinel lymph nodes are imaged or detected bilaterally In primary tumors in stage T IA 1 L1 and/or FIGO IA 2 In primary tumors in stage T IB1 (≤ 2 cm) Removal of all imaged or detected sentinel lymph nodes	EC
8.4. modified 2021	Evidence-based statement If the sentinel lymphadenectomy method alone is being carried out, the following staining methods must be used: Staining demonstration or detection using patent blue and radioactive tracer or Staining demonstration or detection using indocyanine green Primary tumor < 2 cm in size, with no risk factors Removal of all sentinel lymph nodes identified using imaging	A	2++	25  –  27

No.	Recommendations/Statements	GoR	LoE	Sources
8.5. reviewed 2021	Evidence-based recommendation Following pelvic lymphadenectomy, placement of a retroperitoneal drain in the surgical area should be avoided, in order to prevent lymphoceles.	B	1+	28

No.	Recommendations/Statements	GoR	LoE	Sources
8.6. reviewed 2021	Evidence-based recommendation Neoadjuvant drug therapy can be carried out in selected patients who are at high-risk.	0	1−	29 ,  30
8.7. reviewed 2021	Consensus-based recommendation after systematic research The significance of tumor-affected lymph nodes after neoadjuvant chemotherapy for further treatment planning is unclear.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
8.8. reviewed 2021	Consensus-based recommendation after systematic research Adjuvant therapy following primary surgical therapy should be administered on the basis of the postoperative histological tumor stage as follows: Negative lymph nodes; R0; no risk factors Follow-up Negative lymph nodes; R0; one or two risk factors (L1, V1, deep stromal invasion, tumor size > 4 cm) Individualized decision Histologically confirmed lymph-node metastases, pelvic (pN1) or R1 or several (≥ 3) simultaneous risk factors (L1, V1, deep stromal invasion, tumor size > 4 cm, as well as grade G3 if two additional risk factors are present) Adjuvant radio(chemo)therapy including lymphatic drainage areas in the histologically identified area (pelvic) Histologically confirmed para-aortic lymph-node metastases (pM1) Extended adjuvant radio(chemo)therapy including lymphatic drainage areas in the histologically identified area (pelvic and para-aortic fields) Distant metastases, M1 (organ metastases, peritoneal carcinosis, ovarian metastases) Systemic chemotherapy; radiotherapy only indicated in case of bleeding problems	EC

No.	Recommendations/Statements	GoR	LoE	Sources
8.9. reviewed 2021	Consensus-based recommendation after systematic research In stages ≤ FIGO stage IIA, primary surgical therapy should be carried out if adjuvant therapy is not expected (no preoperative risk factors).	EC

No.	Recommendations/Statements	GoR	LoE	Sources
8.10. modified 2021	Consensus-based recommendation In stage IA1 without any risk factors, treatment must be administered as follows: Surgery: Lymph-node removal is not indicated. If family planning has been completed, or if the patient wishes greater certainty: Simple hysterectomy. If the patient wishes to have children: Conization (within healthy margins) with cervical curettage. If there are positive margins in the conization specimen (R1): Repeat conization, or Trachelectomy (within healthy margins, with prophylactic permanent cerclage). Following successful pregnancy: Secondary hysterectomy is possible, particularly if there is persistent HPV, abnormal Pap findings, if the patient wishes maximum safety, or if the cervix is difficult or impossible to assess. Radio(chemo)therapy: Not indicated.	EC
8.11. new 2021	Consensus-based recommendation In stage IA1 with lymphatic infiltration (L1), treatment must be administered as follows: Surgery: Sentinel lymphadenectomy is indicated. If family planning has been completed, or if the patient wishes greater certainty: Simple hysterectomy. If the patient wishes to have children: Conization (within healthy margins) with cervical curettage. If there are positive margins in the conization specimen (R1): Repeat conization, or Trachelectomy (within healthy margins, with prophylactic permanent cerclage). Following successful pregnancy: Secondary hysterectomy is possible, particularly if there is persistent HPV, abnormal Pap findings, if the patient wishes maximum safety, or if the cervix is difficult or impossible to assess. Radio(chemo)therapy: Not indicated.	EC
8.12. modified 2021	Consensus-based recommendation In stage IA1 with at least two risk factors, and stage IA2 with up to one risk factor, treatment should be administered as follows: Surgery: If the patient does not wish to have children and if she wants to be particularly safe and has histologically negative lymph nodes (pelvic) after surgical staging with SNB: Hysterectomy (with bilateral adnexectomy if appropriate), without resection of the parametria (Piver I) If the patient wishes to have children and has negative lymph nodes after surgical staging with SNB: Conization with cervical curettage or Radical trachelectomy with prophylactic permanent cerclage. If there are sentinel lymph nodes affected by tumor, or there are pelvic lymph-node metastases: Para-aortic lymphadenectomy (surgical staging). In premenopausal patients: Ovariopexy to maintain intrinsic ovarian function. If there are macroscopically tumor-affected pelvic and/or para-aortic lymph nodes: Surgical removal before radio(chemo)therapy. After successful pregnancy: Secondary hysterectomy, particularly when there is persistent HPV infection, Pap abnormalities, if the patient wants greater safety, and if the cervix can only be assessed to a limited extent or not at all. Radio(chemo)therapy: If there is histological evidence of pelvic and/or para-aortic lymph-node metastases or there are several risk factors: R(CH)T in the histologically confirmed area of spread.	EC
8.13. modified 2021	Consensus-based recommendation In stage IA2 with at least two risk factors, treatment should be administered as follows: Surgery (preserving fertility is not possible) with SNB: With negative lymph nodes (pelvic) after surgical staging: Radical hysterectomy (with bilateral adnexectomy if appropriate), with resection of the parametria (Piver II) If there are sentinel lymph nodes affected by tumor or if there are pelvic lymph-node metastases: Additional para-aortic lymphadenectomy (surgical staging). In premenopausal patients: Ovariopexy to maintain intrinsic ovarian function. If there are macroscopically tumor-affected pelvic and/or para-aortic lymph nodes: Surgical removal of these before radio(chemo)therapy. Radio(chemo)therapy: If there is histological evidence of pelvic and/or para-aortic lymph-node metastases or there are several risk factors: R(CH)T in the histologically confirmed area of spread.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
8.14. modified 2021	Consensus-based recommendation In stages IB1 and IIA1, treatment should be administered as follows: Surgery: If there are negative lymph nodes (pelvic) after surgical staging: Radical hysterectomy with resection of the medial (near the uterus) half of the parametria, with an adequate safety margin and resection within healthy margins (Piver II). With a tumor-free resection margin at the vaginal cuff (IIA1). If the tumor is < 2 cm, with no risk factors: Surgical staging with SNB and Radical hysterectomy with resection of the medial (near the uterus) half of the parametria, with an adequate safety margin and resection within healthy margins (Piver II). With a tumor-free resection margin at the vaginal cuff (IIA1). If the patient is wishing to have children and the tumor is < 2 cm without risk factors: Surgical staging with SNB and Radical trachelectomy with prophylactic permanent cerclage. If family planning has been completed: Secondary hysterectomy. If there are pelvic lymph-node metastases: Additional para-aortic lymphadenectomy (surgical staging). In postmenopausal patients: Bilateral adnexectomy. In premenopausal patients: Ovariopexy to maintain intrinsic ovarian function. If there are pelvic and/or para-aortic lymph nodes macroscopically affected by tumor: Surgical removal of the nodes, or radio(chemo)therapy. Radio(chemo)therapy: When there is histological evidence of pelvic and/or para-aortic lymph-node metastases, or several confirmed risk factors: R(CH)T. If the patient is inoperable or requests it: R(CH)T. The radiation volume should be based on the anatomy and histologically confirmed lymph-node involvement.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
8.15. reviewed 2021	Consensus-based recommendation In stages IB2, IIA2, and IIB with a maximum of two risk factors, treatment should be administered as follows: Surgery: With negative lymph nodes (pelvic) after surgical staging: Radical hysterectomy (with bilateral adnexectomy if appropriate), Piver type III. With tumor-free resection margin at the vaginal cuff. When there are pelvic lymph-node metastases: Additional para-aortic lymphadenectomy (surgical staging). When there are pelvic and/or para-aortic lymph-nodes with macroscopic tumor involvement: Surgical removal of these before radio(chemo)therapy. When there is vaginal involvement: (Partial) radical colpectomy, with a tumor-free resection margin. In postmenopausal patients: Bilateral adnexectomy. In premenopausal patients with adenocarcinoma: Bilateral adnexectomy. In premenopausal patients with squamous cell carcinoma: Pre-treatment ovariopexy to preserve intrinsic ovarian function, both before planned R(CH)T and also during surgery with necessary adjuvant therapy. Radio(chemo)therapy: With histologically confirmed pelvic and/or para-aortic lymph-node metastases, or with several risk factors: R(CH)T. When the patient is inoperable or requests it: R(CH)T. Stage IIB: Preferably R(CH)T. The radiation volume should be based on the anatomy and histologically confirmed lymph-node involvement.	EC
8.16. modified 2021	Consensus-based statement after systematic research Radical hysterectomy before planned radio(chemo)therapy offers no benefits for the patient in relation to disease-free survival or overall survival.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
8.17. reviewed 2021	Consensus-based recommendation In stage III , the following treatment should be administered: Surgery: Histological verification of spread Surgical staging or interventional clarification. When there are pelvic and/or para-aortic lymph nodes with macroscopic tumor involvement: Surgical removal before radio(chemo)therapy. Radio(chemo)therapy: R(CH)T after surgical staging.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
8.18. reviewed 2021	Consensus-based recommendation In stage IVA, treatment should be administered as follows: Surgery: In selected cases: Primary exenteration. Radio(chemo)therapy: R(CH)T is the treatment of choice.	EC
8.19. reviewed 2021	Consensus-based recommendation In stage IVB, treatment should be administered as follows: Surgery: Symptom-oriented therapy. Radiotherapy or radio(chemo)therapy: Symptom-oriented therapy. Drug therapy: Palliative systemic therapy is the treatment of choice. Additional measures: Best supportive care. Palliative medicine: Early palliative medicine intervention.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
9.1. reviewed 2021	Consensus-based recommendation In postmenopausal patients with macroinvasive carcinoma, bilateral adnexectomy should be carried out during hysterectomy.	EC
9.2. new 2021	Evidence-based recommendation Open radical hysterectomy should be offered to patients up to FIGO stage IB1.	B	1+	31

No.	Recommendations/Statements	GoR	LoE	Sources
9.3. reviewed 2021	Consensus-based statement after systematic research The value of secondary hysterectomy after primary radio(chemo)therapy is unclear in relation to the rate of local recurrence, disease-free survival, metastasis-free survival, and overall survival.	EC
9.4. reviewed 2021	Consensus-based statement Hysterectomy after primary radio(chemo)therapy in patients with complete remission on clinical and imaging findings is associated with a higher morbidity rate in comparison with primary radio(chemo)therapy alone.	EC
9.5. reviewed 2021	Consensus-based statement after systematic research It is unclear whether secondary hysterectomy should be carried out in the form of simple or radical hysterectomy after primary R(CH)T.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
10.1. modified 2021	Evidence-based recommendation Intensity-modulated techniques should be used to achieve optimal sparing of the surrounding tissue during primary radiochemotherapy for cervical carcinoma.	B	1+	32

No.	Recommendations/Statements	GoR	LoE	Sources
10.2. reviewed 2021	Guideline-adapted recommendation Brachytherapy should be a component of the curative treatment approach in primary treatment for cervical carcinoma that includes radio(chemo)therapy.	B	4	6
10.3. modified 2021	Consensus-based recommendation MRI-planned brachytherapy should be used in primary radiochemotherapy for cervical carcinoma, to reduce the rate and severity of gastrointestinal and urogenital toxicities.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
10.4. reviewed 2021	Evidence-based recommendation In patients with cervical carcinoma in whom there is an indication for primary radiotherapy from stage IB2 onwards, the radiotherapy must be combined with cisplatin-based chemotherapy.	A	1++	33 ,  34

No.	Recommendations/Statements	GoR	LoE	Sources
10.5. reviewed 2021	Consensus-based recommendation Adjuvant cisplatin-containing radiochemotherapy should be used in patients with histologically confirmed postoperative risk factors.	B	1−	35 ,  36

No.	Recommendations/Statements	GoR	LoE	Sources
10.6. reviewed 2021	Evidence-based statement The value of consolidating chemotherapy after the completion of radio(chemo)therapy has not been confirmed.	ST	1−	37 ,  38

No.	Recommendations/Statements	GoR	LoE	Sources
10.7. reviewed 2021	Consensus-based recommendation Neoadjuvant radio(chemo)therapy should not be administered outside of research studies.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
10.8. reviewed 2021	Consensus-based recommendation Young patients should be offered ovariopexy and high-conformal radiotherapy techniques to preserve ovarian hormone function.	EC

No.	Recommendations/Statements	GoR	LoE	Sources
10.9. modified 2021	Guideline-adapted recommendation During radiotherapy or radio(chemo)therapy for cervical carcinoma, the patientʼs hemoglobin values should be monitored and corrected via transfusion at values below 10 g/dL (6.2 mmol/L).	B	2++	6

No.	Recommendations/Statements	GoR	LoE	Sources
10.10. reviewed 2021	Evidence-based recommendation Locoregional hyperthermia can be used in combination with percutaneous radiotherapy to treat locoregional recurrence or primary cervical carcinoma ≥ FIGO stage IIB.	0	1−	39
10.11. modified 2021	Evidence-based statement No advantage in relation to overall survival or disease-free survival has so far been confirmed in randomized trials, with the addition of locoregional hyperthermia to primary radiochemotherapy for cervical carcinoma.	ST	1−	40
10.12. reviewed 2021	Consensus-based recommendation Locoregional hyperthermia must be administered in a quality-assured and standardized fashion, preferably in the framework of scientific studies.	EC

Nr.	Empfehlungen/Statements	EG	LoE	Quellen
4.1. geprüft 2021	Empfehlungen zu Prävention und Früherkennung des Zervixkarzinoms werden in den S3-Leitlinien „Impfprävention HPV-assoziierter Neoplasien (AWMF-Registernummer 082/002)“ und „Prävention des Zervixkarzinoms (AWMF-Registernummer 015/027OL)“ bearbeitet.	EK

Nr.	Empfehlungen/Statements	EG	LoE	Quellen
5.1. geprüft 2021	Qualifizierte und sachdienliche Informationsmaterialien (Print- oder Internetmedien) sollen nach definierten Qualitätskriterien für Gesundheitsinformationen erstellt und Patientinnen zur Verfügung gestellt werden, um sie durch eine allgemeinverständliche Risikokommunikation (z. B. Angabe von absoluten Risikoreduktionen) in ihrer selbstbestimmten Entscheidung für oder gegen medizinische Maßnahmen zu unterstützen.	EK

Nr.	Empfehlungen/Statements	EG	LoE	Quellen
5.2. geprüft 2021	Der Patientin soll angeboten werden, den Partner/die Partnerin oder Angehörige in das Gespräch bzw. die Gespräche einzubeziehen.	EK
5.3. geprüft 2021	Im ärztlichen Gespräch sollen die individuellen Präferenzen, Bedürfnisse, Sorgen und Ängste der Patientin eruiert und berücksichtigt werden. Wenn eine Patientin dafür mehrere Gespräche benötigt, soll das Angebot zu weiteren Gesprächen bestehen.	EK
5.4. mod. 2021	Die medizinische Aufklärung der Patientin ist primär Aufgabe des behandelnden Arztes, sie sollte jedoch bei spezifischen Themen durch andere Berufsgruppen wie Pflege, Psychoonkologen etc. erbracht werden.	EK
5.5. mod. 2021	Die Art der Vermittlung von Informationen und der Aufklärung der Patientin soll möglichst frühzeitig nach folgenden Grundprinzipien einer patientinnenzentrierten Kommunikation, die eine partizipative Entscheidungsfindung ermöglicht, erfolgen: Ausdruck von Empathie und aktives Zuhören, direktes und einfühlsames Ansprechen schwieriger Themen, Vermeidung von medizinischem Fachvokabular, ggf. Erklärung von Fachbegriffen, Strategien, um das Verständnis zu verbessern (Wiederholung, Zusammenfassung wichtiger Informationen, Nutzung von Grafiken u. a.), Ermutigung, Fragen zu stellen, Erlaubnis und Ermutigung, Gefühle auszudrücken, weiterführende Hilfe anbieten.	EK
5.6. geprüft 2021	Der Patientin sollte eine psychosoziale und psychoonkologische Unterstützung bei psychischen, sexuellen oder partnerschaftlichen Problemen angeboten werden.	EK
5.7. geprüft 2021	Die Patientin soll auf die Möglichkeit, Selbsthilfegruppen zu kontaktieren, hingewiesen werden.	EK

Nr.	Empfehlungen/Statements	EG	LoE	Quellen
5.8. geprüft 2021	Gemäß dem „Gesetz zur Verbesserung der Rechte von Patientinnen und Patienten“ soll die Patientin über alle in dieser Leitlinie beschriebenen für sie relevanten Therapieoptionen, deren Erfolgsaussichten und deren mögliche Auswirkungen informiert werden. Insbesondere soll auf die Auswirkungen auf ihr körperliches Erscheinungsbild, ihr Sexualleben, ihre Harn- und Stuhlkontrolle (Inkontinenz) und Aspekte des weiblichen Selbstverständnisses (Selbstbild, Fertilität) eingegangen werden.	EK
5.9. geprüft 2021	Prinzipien, angestrebte Behandlungsziele, Dauer und die Durchführung der einzelnen Therapiemaßnahmen Operative Therapiemaßnahmen: Konisation; Trachelektomie operatives Staging und die damit einhergehenden weiteren Maßnahmen Formen der Lymphadenektomie Formen der radikalen Hysterektomie exenterative Verfahren operative Behandlungsmöglichkeiten des Rezidivs Strahlentherapie: primäre Radiatio/Radio(chemo) therapie sekundäre Radiatio/Radio(chemo) therapie systemische Therapie: neoadjuvante/adjuvante Chemotherapie kombinierte Radio(chemo)therapie zielgerichtete Therapie Nebenwirkungen der Therapie und ihre Behandlungsmöglichkeiten Spätfolgen der Erkrankung und der Therapie und ihre Behandlungsmöglichkeiten komplementäre Therapie: Erfassen des Hinzuziehens von Komplementärmedizin zur Reduktion von Nebenwirkungen Teilnahme an klinischen Studien: Prinzipien und angestrebte Behandlungsziele Dauer und Durchführung der Therapie bisher bekannte Wirkungen und Nebenwirkungen Besonderheiten (Monitoring, zusätzliche Maßnahmen, Mitwirkung, Datenspeicherung und -verarbeitung) sonstige Informationen: psychoonkologische Unterstützung sowie Leistungen der Selbsthilfegruppen Möglichkeiten der Rehabilitation Notwendigkeit der Nachsorge Aspekte der Eigenverantwortung und Mitwirkung (z. B. Mitteilung von Symptomen und Problemen, Therapiecompliance)	EK
5.10. geprüft 2021	Die Patientin soll auf die Patientinnen-Leitlinie zur Diagnostik, Therapie und Nachsorge der Patientin mit Zervixkarzinom hingewiesen werden.	EK
5.11. geprüft 2021	Die Erkrankung Zervixkarzinom ist kein Notfall! Der Patientin ist für ihren Entscheidungsprozess ausreichend Zeit einzuräumen.	EK

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5.12. geprüft 2021	Als Inhalte eines Gesprächs in der Palliativsituation können folgende Punkte angesprochen werden: Ziele der palliativmedizinischen Therapie (Linderung von Leiden, Behandlung von Schmerzen – oberstes Ziel: Lebensqualität der Patientin): Ängste und Befürchtungen der Patientin mit Einbeziehung von Partner und Angehörigen Radio(chemo)therapie, Dauer und damit angestrebtes Ziel palliative medikamentöse Behandlung palliative operative Behandlung individuelle Therapieentscheidungen abhängig von der persönlichen Lebensplanung der Patientin bei eingeschränkten Therapieeffekten kann das Ergebnis der Entscheidungsfindung der bewusste Verzicht auf palliative Tumortherapie sein Verweis auf Palliativkapitel (Rehabilitation, Psychosoziale Medizin, Psychoonkologie) Nebenwirkungen und Interaktionen von Medikamenten und Komplementärmedizin ggf. Einbinden der lokalen Hospizinitiative Hinzuziehen palliativmedizinisch spezialisierter Ärzte und Pflegedienste Problemsituationen im Krankheitsverlauf: Schmerzen Ureterstenosen mit konsekutivem Nierenversagen Fisteln fötider Ausfluss Blutungen paralytischer oder mechanischer Ileus Thrombose, Lungenembolie symptomatische, supportive Therapie (Verweis Supportivtherapie): Behandlung von Lymphödemen der unteren Extremitäten Schmerztherapie Dysurie/Blasenspasmen psychosoziale und religiöse/spirituelle Begleitung der Patientin sowie ihrer Angehörigen Hilfsmittel	EK

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6.1. mod. 2021	Zur Festlegung der lokalen Tumorausbreitung soll klinisch bildgebend der vaginale Ultraschall und zum Ausschluss einer Harntransportstörung der Nierenultraschall durchgeführt werden.	EK
6.2. mod. 2021	Patientinnen mit histologisch gesichertem Zervixkarzinom ab mindestens FIGO-Stadium IB2 und bis einschließlich III sollten eine MRT-Becken zur Beurteilung der lokoregionären Tumorausbreitung erhalten.	B	1+	5  –  7
6.3. mod. 2021	Bei Patientinnen ab mindestens FIGO IB2 bis einschließlich III, bei denen aus technischen Gründen eine MRT-Becken nicht durchgeführt werden kann, sollte das lokoregionäre bildgebende Staging des Beckens im Rahmen der Staging-CT-Thorax/Abdomen/Becken-Untersuchung erfolgen.	EK
6.4. neu 2021	Bei Patientinnen im Stadium FIGO IVA, bei denen aus technischen Gründen eine MRT-Becken nicht durchgeführt werden kann, sollte das lokoregionäre bildgebende Staging des Beckens im Rahmen der Staging-CT-Thorax/Abdomen/ Becken-Untersuchung erfolgen.	EK
6.5. mod. 2021	Patientinnen mit histologisch gesichertem Zervixkarzinom ab mindestens FIGO-Stadium IB2 sollten ein CT-Thorax/Abdomen/Becken zur Beurteilung der Tumorausbreitung erhalten.	EK
6.6. geprüft 2021	Bei makroskopisch nicht sicher beurteilbarem Tumor der Portio soll eine Differenzialkolposkopie und gezielte Biopsie erfolgen.	EK
6.7. geprüft 2021	Grundlage der interdisziplinären Therapieentscheidung in der Tumorkonferenz sollte das histologisch gesicherte Tumorstadium sein.	EK
6.8. mod. 2021	Das PET-CT sollte zur Therapieplanung des primären Zervixkarzinoms nicht eingesetzt werden.	B	2+	6 ,  8  –  11
6.9. mod. 2021	Bei Erwägung eines lokalen Verfahrens (RCHT, Exenteration) zur Therapie eines Rezidivs sollte zum Ausschluss von Lymphknoten- und Fernmetastasen eine PET-CT durchgeführt werden.	B	2+	6 ,  12  –  14

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7.1. geprüft 2021	Die Tumortypisierung des Zervixkarzinoms soll nach der aktuell gültigen Auflage der WHO-Klassifikation erfolgen.	EK
7.2. geprüft 2021	Bei Zervixkarzinomen mit neuroendokriner Komponente soll diese mit Angabe des Prozentsatzes am Gesamttumor ausgewiesen werden.	EK

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7.3. mod. 2021	Die Stadieneinteilung des Zervixkarzinoms soll nach der aktuellen Auflage der TNM-Klassifikation erfolgen.	EK
7.4. geprüft 2021	Der Diagnose eines mikroinvasiven Zervixkarzinoms soll die Definition der jeweils aktuellen Auflage der WHO- und TNM-Klassifikation zugrunde gelegt werden.	EK

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7.5. geprüft 2021	Das entnommene Biopsat soll in Stufenschnitten aufgearbeitet werden.	EK
7.6. mod. 2021	Der Befundbericht sollte zum Nachweis und zum Grad der CIN, eines AIS (und dessen Variante in Form der stratifizierten muzinproduzierenden Läsion [SMILE]) sowie zu virusassoziierten Veränderungen und einer eventuellen Invasion Stellung nehmen.	EK

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7.7. geprüft 2021	Der pathologische Befundbericht soll zur Größe und Beschaffenheit des Exzidates (Konisates) Stellung nehmen. Das Konisat soll vollständig aufgearbeitet und von jedem Paraffinblock sollen Stufenschnitte angefertigt werden.	EK
7.8. mod. 2021	Im histologischen Befundbericht vermerkt sein sollen die Art der Läsion (CIN, AIS und dessen Variante in Form der stratifizierten muzinproduzierenden Läsion [SMILE]), deren Lokalisation (endo-, ektozervikal) und deren Ausdehnung sowie das Vorhandensein eines invasiven Tumors. Beim Nachweis einer Invasion soll zusätzlich die Angabe der Größenausdehnung erfolgen und zur Lymph-, Blutgefäß- sowie Perineuralscheideninvasion sowie zum Grading Stellung bezogen werden. Zum Status der Resektionsränder soll Stellung genommen werden.	EK
7.9. neu 2021	Ein multifokales mikroinvasives Karzinom ist definiert als der Nachweis voneinander histologisch klar separierter invasiver Foci, die einen minimalen Abstand von 0,2 cm aufweisen. Jeder invasive Tumorfokus soll separat in seiner Größe angegeben werden, wobei die größte Einzelläsion stagingrelevant ist.	EK

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7.10. geprüft 2021	Die morphologische Aufarbeitung soll so erfolgen, dass alle therapeutisch und prognostisch relevanten Parameter erhoben werden können. Der Befunderstellung soll die jeweils gültige WHO-Klassifikation zur Tumortypisierung und die aktuelle TNM-Klassifikation zur Stadieneinteilung sowie die R-Klassifikation (UICC) zugrunde gelegt werden.	EK
7.11. mod. 2021	Der Befundbericht zur Trachelektomie soll folgende Angaben beinhalten: histologischer Typ nach WHO, Grading, Nachweis/Fehlen von Lymph- oder Veneneinbrüchen (L- und V-Status), Nachweis/Fehlen von Perineuralscheideninfiltraten (Pn-Status), Staging (TNM), Invasionstiefe und Ausdehnung in mm bei pT1a1 und pT1a2, dreidimensionale Tumorgröße in cm (ab pT1b1), minimaler Abstand zu den Resektionsrändern (bei pT1b-Tumoren endozervikales Stroma), R-Klassifikation (UICC).	EK

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7.12. geprüft 2021	Die morphologische Aufarbeitung soll so erfolgen, dass alle therapeutisch und prognostisch relevanten Parameter erhoben werden können. Der Befunderstellung soll die jeweils gültige WHO-Klassifikation zur Tumortypisierung und die aktuelle TNM-Klassifikation zur Stadieneinteilung sowie die R-Klassifikation (UICC) zugrunde gelegt werden.	EK
7.13. neu 2021	Zur Dokumentation einer intratumoralen Heterogenität sollen makroskopisch sichtbare Tumoren ≤ 2 cm vollständig aufgearbeitet und von Tumoren ab 2 cm Größe mindestens ein Block pro Zentimeter größter Tumorausdehnung eingebettet werden.	EK
7.14. geprüft 2021	Eine tiefe Stromainfiltration ist definiert als die Invasion des Zervixkarzinoms bis in das äußere Drittel des zervikalen Stromas (> 66%).	EK
7.15. mod. 2021	Der Befundbericht zur radikalen Hysterektomie soll folgende Angaben beinhalten: histologischer Typ nach WHO, Grading, Nachweis/Fehlen von Lymph- oder Veneneinbrüchen (L- und V-Status), Nachweis/Fehlen von Perineuralscheideninfiltraten (Pn-Status), Staging (TNM), bei konisierten Patientinnen unter Berücksichtigung des Konisationsbefundes, Invasionstiefe und Ausdehnung in mm bei pT1a1 und pT1a2, Invasionstiefe in Relation zur Zervixwanddicke (metrisch oder Prozentangabe) dreidimensionale Tumorgröße in cm (ab pT1b1), minimaler Abstand zu den Resektionsrändern (bei pT1b-Tumoren endozervikales Stroma, pT2a-Tumoren Vagina, pT2b Parametrium), R-Klassifikation (UICC).	EK

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7.16. geprüft 2021	Mikrometastasen sind definiert als der histologische Nachweis von Tumorzellen im Lymphknoten von ≥ 0,2 mm, aber nicht größer als 0,2 cm.	EK
7.17. geprüft 2021	Bei Lymphonodektomiepräparaten im Rahmen der operativen Therapie beim Zervixkarzinom sollen alle entfernten Lymphknoten histologisch untersucht werden.	EK
7.18. geprüft 2021	Lymphknoten bis ca. 0,3 cm Größe sollten komplett eingebettet und größere Lymphknoten entlang ihrer Längsachse halbiert und ebenfalls komplett eingebettet werden.	EK
7.19. neu 2021	Der Nachweis von isolierten Tumorzellen bzw. von Mikrometastasen soll im histologischen Befundbericht erwähnt werden und in die TNM-Klassifikation einfließen.	EK
7.20. geprüft 2021	Der Befundbericht zu den Lymphknoten soll folgende Angaben beinhalten: Angabe der Zahl der befallenen Lymphknoten im Verhältnis zur Zahl der entfernten Lymphknoten in Zuordnung zur Entnahmelokalisation (pelvin/paraaortal)	EK

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7.21. geprüft 2021	Sentinel-Lymphknoten beim Zervixkarzinom sollen vollständig eingebettet und in Stufenschnitten untersucht werden.	EK
7.22. neu 2021	Sentinel-Lymphknoten beim Zervixkarzinom sollten wie folgt aufgearbeitet werden: Lamellierung des übersandten Fettgewebes mit Identifikation aller Sentinel-Lymphknoten, vollständige Entfernung aller Lymphknoten, Halbierung aller Lymphknoten ≤ 0,3 cm Größe, Lamellierung aller Lymphknoten > 0,3 cm in 0,2 cm dicke Lamellen, Anfertigung von Stufenschnitten, immunhistochemisches Ultrastaging, vollständige Einbettung des Fettgewebes bei makroskopisch nicht identifizierbaren Sentinel-Lymphknoten.	EK
7.23. neu 2021	Die intraoperative Schnellschnittuntersuchung (wenn klinisch indiziert) von Sentinel-Lymphknoten beim Zervixkarzinom soll wie folgt durchgeführt werden: Aufarbeitung der Sentinel-Lymphknoten nach Standard, Untersuchung aller Sentinel-Lymphknoten im Schnellschnitt, bei makroskopisch sichtbarem Tumor ist die intraoperative Untersuchung einer Probe des befallenen Lymphknotens ausreichend, makroskopisch unauffällige Lymphknoten sollen vollständig intraoperativ untersucht werden, von den Gefrierblöckchen sollen (3) Stufenschnitte angefertigt werden, die histologische Gefrierschnittuntersuchung kann durch eine intraoperative Imprintzytologie ergänzt werden.	EK

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8.1. geprüft 2021	Ziel der Therapie des primären Zervixkarzinoms sollte eine individuelle Therapie sein. Die Therapiewahl sollte unter Berücksichtigung folgender Faktoren erfolgen: des Allgemeinzustands (bei hoher Komorbidität), der Lebenssituation der Patientin, des klinisch/histologisch definierten Stadiums der Erkrankung, des Menopausenstatus, des potenziellen Kinderwunschs, der Kurz- und Langzeitfolgen der verschiedenen Therapiemöglichkeiten, etwaiger Risikofaktoren. Über- bzw. Untertherapien sollten vermieden werden.	EK

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8.2. geprüft 2021	Die Therapie soll in Abhängigkeit des histologischen Tumorstadiums erfolgen, verifiziert mittels operativem Staging oder interventioneller Diagnostik.	EK
8.3. mod. 2021	Die alleinige Sentinel-Lymphonodektomie sollte eingesetzt werden bei: präoperativer Darstellung (Patentblau und radioaktiv), oder intraoperativer Darstellung (Indocyaningrün), bei Darstellung bzw. Detektion von Sentinel-Lymphknoten beidseits , bei Primärtumoren im Stadium T IA 1 L1 und/oder FIGO IA 2, bei Primärtumoren im Stadium T IB1 (≤ 2 cm), Entfernung aller dargestellten bzw. detektierten Sentinel-Lymphknoten.	EK
8.4. mod. 2021	Wenn die alleinige Sentinel-Lymphonodektomiemethode durchgeführt wird, sollen folgende Färbemethoden durchführt werden: Anfärbung Darstellung bzw. Detektion mittels Patentblau und radioaktivem Tracer oder Anfärbung Darstellung bzw. Detektion mittels Indocyaningrün.	A	2++	25  –  27

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8.5. geprüft 2021	Nach pelviner Lymphonodektomie sollte auf die Einlage einer retroperitonealen Drainage in das OP-Gebiet zur Vermeidung von Lymphozysten verzichtet werden.	B	1+	28

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8.6. geprüft 2021	Eine medikamentöse neoadjuvante Therapie kann bei ausgewählten Risikopatientinnen durchgeführt werden.	0	1−	29 ,  30
8.7. geprüft 2021	Die Bedeutung tumorbefallener Lymphknoten nach neoadjuvanter Chemotherapie für die weitere Therapieplanung ist unklar.	EK

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8.8. geprüft 2021	Die adjuvante Therapie nach primär operativer Therapie sollte anhand des postoperativen histologischen Tumorstadiums folgendermaßen erfolgen: negative Lymphknoten; R0; keine Risikofaktoren Nachsorge negative Lymphknoten; R0; 1 oder 2 Risikofaktoren (L1, V1, tiefe Stromainvasion, Tumorgröße > 4 cm) individuelle Entscheidung histologisch gesicherte Lymphknotenmetastasen pelvin (pN1) oder R1 oder simultan mehrere [≥ 3] Risikofaktoren (L1, V1, tiefe Stromainvasion, Tumorgröße > 4 cm sowie Grading G3, falls 2 weitere Risikofaktoren vorliegen) adjuvante Radio(chemo)therapie inklusive Lymphabflussgebiete des histologisch nachgewiesenen Bereichs (pelvin) histologisch gesicherte Lymphknotenmetastasen paraaortal (pM1) erweiterte adjuvante Radio(chemo)therapie inklusive Lymphabflussgebiete des histologisch nachgewiesenen Bereichs (pelvin und paraaortales Feld) Fernmetastasen M1 (Organmetastasen, Peritonealkarzinose, Ovarmetastasen) systemische Chemotherapie; Radiotherapie nur bei Blutungsproblematik indiziert	EK

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8.9. geprüft 2021	In den Stadien ≤ FIGO-Stadium IIA sollte bei nicht zu erwartender adjuvanter Therapie (fehlende präoperative Risikofaktoren) die primär operative Therapie erfolgen.	EK

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8.10. mod. 2021	Im Stadium IA1 ohne Risikofaktor soll folgendermaßen therapiert werden: Operation: Lymphknotenentfernung ist nicht indiziert. nach abgeschlossener Familienplanung bzw. bei Sicherheitsbedürfnis der Patientin: einfache Hysterektomie bei Kinderwunsch: Konisation (in sano) mit Zervixkürettage bei positiven Rändern im Konisat (R1): Wiederholung der Konisation oder Durchführung einer Trachelektomie (in sano, mit prophylaktischer Permanentcerclage) nach erfolgreicher Schwangerschaft: sekundäre Hysterektomie möglich, v. a. bei HPV-Persistenz, Pap-Auffälligkeiten, Wunsch nach maximaler Sicherheit, eingeschränkter oder aufgehobener Beurteilbarkeit der Zervix Radio(chemo)therapie: nicht indiziert	EK
8.11. neu 2021	Im Stadium IA1 mit Lymphgefäßinfiltration (L1) soll folgendermaßen therapiert werden: Operation: Sentinel-Lymphonodektomie ist indiziert. nach abgeschlossener Familienplanung bzw. bei Sicherheitsbedürfnis der Patientin: einfache Hysterektomie bei Kinderwunsch: Konisation (in sano) mit Zervixkürettage bei positiven Rändern im Konisat (R1): Wiederholung der Konisation oder Durchführung einer Trachelektomie (in sano, mit prophylaktischer Permanentcerclage) nach erfolgreicher Schwangerschaft: sekundäre Hysterektomie möglich, v. a. bei HPV-Persistenz, Pap-Auffälligkeiten, Wunsch nach maximaler Sicherheit, eingeschränkter oder aufgehobener Beurteilbarkeit der Zervix Radio(chemo)therapie: nicht indiziert	EK
8.12. mod. 2021	Im Stadium IA1 mit mindestens 2 Risikofaktoren und Stadium IA2 mit bis zu 1 Risikofaktor sollte folgendermaßen therapiert werden: Operation: nach abgeschlossener Familienplanung bzw. bei besonderem Sicherheitsbedürfnis der Patientin und histologisch negativen Lymphknoten (pelvin) nach operativem Staging mittels SNB: Hysterektomie (ggf. mit Adnexektomie beidseits) ohne Resektion der Parametrien (Piver I) bei Kinderwunsch und histologisch negativen Lymphknoten nach Operativem Staging mittels SNB: Konisation mit Zervixkürettage oder radikale Trachelektomie mit prophylaktischer Permanentcerclage bei tumorbefallenen Sentinel-Lymphknoten oder pelvinen Lymphknotenmetastasen: paraaortale Lymphonodektomie (operatives Staging) bei prämenopausalen Patientinnen: Ovariopexie zum Erhalt der intrinsischen Ovarialfunktion bei makroskopisch tumorbefallenen pelvinen und/oder paraaortalen Lymphknoten: operative Entfernung vor einer Radio(chemo)therapie nach erfolgreicher Schwangerschaft: sekundäre Hysterektomie, v. a. bei HPV-Persistenz, Pap-Auffälligkeiten, Wunsch nach Sicherheit, eingeschränkter oder aufgehobener Beurteilbarkeit der Zervix Radio(chemo)therapie: bei histologisch nachgewiesenen pelvinen und/oder paraaortalen Lymphknotenmetastasen bzw. mehreren Risikofaktoren: R(CH)T im histologisch nachgewiesenen Ausbreitungsfeld	EK
8.13. mod. 2021	Im Stadium IA2 mit mindestens 2 Risikofaktoren sollte folgendermaßen therapiert werden: Operation (kein Fertilitätserhalt möglich) mit SNB: bei negativen Lymphknoten (pelvin) nach operativem Staging: radikale Hysterektomie (ggf. mit Adnexektomie beidseits) mit Resektion der medialen (uterusnahen) Hälfte der Parametrien (Piver II) bei tumorbefallenen Sentinel-Lymphknoten oder pelvinen Lymphknoten-metastasen: zusätzlich paraaortale Lymphonodektomie (operatives Staging) bei prämenopausalen Patientinnen: Ovariopexie zum Erhalt der intrinsischen Ovarialfunktion bei makroskopisch tumorbefallenen pelvinen und/oder paraaortalen Lymphknoten: operative Entfernung derselben vor einer Radio(chemo)therapie Radio(chemo)therapie: bei histologisch nachgewiesenen pelvinen und/oder paraaortalen Lymphknotenmetastasen bzw. mehreren Risikofaktoren: R(CH)T im histologisch nachgewiesenen Ausbreitungsfeld	EK

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8.14. mod. 2021	Im Stadium IB1 und IIA1 sollte folgendermaßen therapiert werden: Operation: bei negativen Lymphknoten (pelvin) nach operativem Staging radikale Hysterektomie mit Resektion der medialen (uterusnahen) Hälfte der Parametrien mit ausreichendem Sicherheitsabstand und Resektion im Gesunden (Piver II) mit tumorfreiem Resektionsrand der Scheidenmanschette (IIA1) bei Tumoren < 2 cm ohne Risikofaktoren: operatives Staging mittels SNB und radikale Hysterektomie mit Resektion der medialen (uterusnahen) Hälfte der Parametrien mit ausreichendem Sicherheitsabstand und Resektion im Gesunden (Piver II) mit tumorfreiem Resektionsrand der Scheidenmanschette (IIA1) bei Kinderwunsch und Tumoren < 2 cm ohne Risikofaktoren: operatives Staging mittels SNB und radikale Trachelektomie mit prophylaktischer Permanentcerclage nach abgeschlossener Familienplanung: sekundäre Hysterektomie bei pelvinen Lymphknotenmetastasen: zusätzlich paraaortale Lymphonodektomie (operatives Staging) bei postmenopausalen Patientinnen: Adnexektomie beidseits bei prämenopausalen Patientinnen: Ovariopexie zum Erhalt der intrinsischen Ovarialfunktion bei makroskopisch tumorbefallenen pelvinen und/oder paraaortalen Lymphknoten: operative Entfernung derselben vor einer Radio(chemo)therapie Radio(chemo)therapie: bei histologisch nachgewiesenen pelvinen und/oder paraaortalen Lymphknotenmetastasen bzw. mehreren nachgewiesenen Risikofaktoren: R(CH)T bei Inoperabilität oder Wunsch der Patientin: R(CH)T Das Bestrahlungsvolumen sollte sich nach der Anatomie und dem histologisch nachgewiesenen Lymphknotenbefall richten.	EK

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8.15. geprüft 2021	Im Stadium IB2, IIA2 und IIB mit maximal 2 Risikofaktoren sollte folgendermaßen therapiert werden: Operation: bei negativen Lymphknoten (pelvin) nach operativem Staging: radikale Hysterektomie (ggf. mit Adnexektomie beidseits) Typ Piver III mit tumorfreiem Resektionsrand der Scheidenmanschette bei pelvinen Lymphknotenmetastasen: zusätzlich paraaortale Lymphonodektomie (operatives Staging) bei makroskopisch tumorbefallenen pelvinen und/oder paraaortalen Lymphknoten: operative Entfernung derselben vor einer Radio(chemo)therapie bei Scheidenbefall: (partielle) radikale Kolpektomie mit tumorfreiem Resektatrand bei postmenopausalen Patientinnen: Adnexektomie beidseits bei prämenopausalen Patientinnen mit Adenokarzinom: Adnexektomie beidseits bei prämenopausalen Patientinnen mit Plattenepithelkarzinom: prätherapeutische Ovariopexie zum Erhalt der intrinsischen Ovarialfunktion, sowohl vor geplanter R(CH)T als auch während der OP bei notwendiger adjuvanter Therapie Radio(chemo)therapie: bei histologisch nachgewiesenen pelvinen und/oder paraaortalen Lymphknotenmetastasen bzw. mehreren Risikofaktoren: R(CH)T bei Inoperabilität oder Wunsch der Patientin: R(CH)T Stadium IIB: R(CH)T bevorzugt Das Bestrahlungsvolumen sollte sich nach der Anatomie und dem histologisch nachgewiesenen Lymphknotenbefall richten.	EK
8.16. mod. 2021	Die radikale Hysterektomie vor der geplanten Radio(chemo)therapie hat keinen Vorteil für das krankheitsfreie Überleben oder das Gesamtüberleben der Patientin.	EK

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8.17. geprüft 2021	Im Stadium III sollte folgendermaßen therapiert werden: Operation: histologische Verifizierung der Ausbreitung operatives Staging oder interventionelle Abklärung bei makroskopisch tumorbefallenen pelvinen und/oder paraaortalen Lymphknoten: operative Entfernung vor einer Radio(chemo)therapie Radio(chemo)therapie: R(CH)T nach operativem Staging	EK

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8.18. geprüft 2021	Im Stadium IVA sollte folgendermaßen therapiert werden: Operation: in ausgesuchten Fällen: primäre Exenteration Radio(chemo)therapie: R(CH)T ist Therapie der Wahl.	EK
8.19. geprüft 2021	Im Stadium IVB sollte folgendermaßen therapiert werden: Operation: symptomorientierte Therapie Radiotherapie oder Radio(chemo) therapie: symptomorientierte Therapie medikamentöse Therapie: Die palliative Systemtherapie ist die Therapie der Wahl. weitere Maßnahmen: Best supportive Care Palliativmedizin: palliativmedizinische Frühintervention	EK

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9.1. geprüft 2021	In der Postmenopause sollte bei makroinvasivem Karzinom eine beidseitige Adnexektomie im Rahmen einer Hysterektomie durchgeführt werden.	EK
9.2. neu 2021	Die offene radikale Hysterektomie sollte den Patientinnen bis FIGO IB1 angeboten werden.	B	1+	31

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9.3. geprüft 2021	Die Wertigkeit der sekundären Hysterektomie nach primärer Radio(chemo)therapie bezogen auf die Lokalrezidivrate, das krankheitsfreie Überleben, das metastasenfreie Überleben oder das Gesamtüberleben ist unklar.	EK
9.4. geprüft 2021	Eine Hysterektomie nach primärer Radio(chemo)therapie bei klinischer und bildgebender Komplettremission hat eine höhere Morbidität im Vergleich zur alleinigen primären Radio(chemo)therapie.	EK
9.5. geprüft 2021	Ob die sekundäre Hysterektomie nach primärer R(CH)T als einfache oder radikale Hysterektomie durchgeführt werden soll, ist unklar.	EK

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10.1. mod. 2021	Intensitätsmodulierte Techniken sollten zur optimalen Schonung des umliegenden Gewebes in der primären Radiochemotherapie des Zervixkarzinoms zum Einsatz kommen.	B	1+	32

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10.2. geprüft 2021	Die Brachytherapie sollte Bestandteil des kurativen Therapiekonzeptes in der Primärtherapie des Zervixkarzinoms, die eine Radio(chemo)therapie beinhaltet, sein.	B	4	6
10.3. mod. 2021	In der primären Radiochemotherapie des Zervixkarzinoms sollte die MRT-geplante Brachytherapie eingesetzt werden, um die Rate und den Schweregrad gastrointestinaler und urogenitaler Toxizitäten zu reduzieren.	EK

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10.4. geprüft 2021	Bei der Patientin mit Zervixkarzinom soll bei Indikationsstellung zu einer primären Radiotherapie ab Stadium IB2 diese in Kombination mit einer cisplatinbasierten Chemotherapie erfolgen.	A	1++	33 ,  34

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10.5. geprüft 2021	Die adjuvante cisplatinhaltige Radiochemotherapie sollte bei Patientinnen mit histologisch gesicherten postoperativen Risikofaktoren zum Einsatz kommen.	B	1−	35 ,  36

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10.6. geprüft 2021	Der Stellenwert der konsolidierenden Chemotherapie nach abgeschlossener Radio(chemo)therapie ist nicht gesichert.	ST	1−	37 ,  38

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10.7. geprüft 2021	Die neoadjuvante Radio(chemo)therapie sollte außerhalb von Studien nicht angewandt werden.	EK

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10.8. geprüft 2021	Zum Erhalt der hormonellen Funktion des Ovars sollte der jungen Patientin die Ovariopexie und hochkonformale Strahlentherapietechniken angeboten werden.	EK

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10.9. mod. 2021	Während einer Radiotherapie oder Radio(chemo)therapie des Zervixkarzinoms sollte der Hämoglobinwert überwacht werden und bei Werten unterhalb von 10 g/dl (6,2 mmol/l) mittels Transfusion korrigiert werden.	B	2++	6

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10.10. geprüft 2021	Die lokoregionäre Hyperthermie kann bei der Therapie des lokoregionären Rezidivs oder des primären Zervixkarzinoms ≥ FIGO-Stadium IIB in Kombination mit der perkutanen Radiotherapie eingesetzt werden.	0	1−	39
10.11. mod. 2021	Ein Vorteil im Gesamtüberleben oder krankheitsfreien Überleben durch Hinzunahme der lokoregionären Hyperthermie zur primären Radiochemotherapie des Zervixkarzinoms konnte in randomisierten Studien bisher nicht nachgewiesen werden.	ST	1−	40
10.12. geprüft 2021	Die lokoregionäre Hyperthermie soll qualitätsgesichert und standardisiert erfolgen, möglichst im Rahmen von wissenschaftlichen Studien.	EK