Radical Versus Simple Hysterectomy and Pelvic Node Dissection With Low-risk Early Stage Cervical Cancer

NCT ID: NCT01658930

Last Updated: 2024-12-17

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

700 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-12-10

Study Completion Date

2024-11-04

Brief Summary

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The reason this study is being done is to see if a simple hysterectomy is as good as a radical hysterectomy in preventing cancer of the cervix from returning, and whether, because less tissue surrounding the uterus is removed during surgery, there are fewer side-effects after the surgery and in the long-term.

Detailed Description

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At this time, it is not clear which of these approaches best balances the desire to prevent cancer of the cervix from returning with the risks of side effects after surgery and in the long-term.

Conditions

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Cervical Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Radical Hysterectomy

Group Type ACTIVE_COMPARATOR

Radical Hysterectomy + pelvic lymph node dissection

Intervention Type PROCEDURE

This procedure may be performed abdominally, laparoscopically, robotically or vaginally. The uterus, cervix, medial 1/3 of parametria, 2cm of the uterosacral ligaments and upper 1-2cm of the vagina are to be removed en bloc. The uterine artery is ligated laterally to the ureters and the ureters are unroofed to the ureterovesical junction.

Simple Hysterectomy

Group Type EXPERIMENTAL

Simple hysterectomy + pelvic lymph node dissection

Intervention Type PROCEDURE

This procedure may be performed abdominally, laparoscopically, robotically or vaginally. Extrafascial hysterectomy involves removal of the uterus with cervix without adjacent parametria. The uterine arteries are transected medial to the ureters at the level of the isthmus and the uterosacral ligaments are transected at the level of the cervix. Surgeons should pay special attention to make sure that the whole cervix is removed. As such, a maximum of 0.5 cm of vaginal cuff can be removed to ensure the complete removal of the cervix.

Interventions

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Radical Hysterectomy + pelvic lymph node dissection

This procedure may be performed abdominally, laparoscopically, robotically or vaginally. The uterus, cervix, medial 1/3 of parametria, 2cm of the uterosacral ligaments and upper 1-2cm of the vagina are to be removed en bloc. The uterine artery is ligated laterally to the ureters and the ureters are unroofed to the ureterovesical junction.

Intervention Type PROCEDURE

Simple hysterectomy + pelvic lymph node dissection

This procedure may be performed abdominally, laparoscopically, robotically or vaginally. Extrafascial hysterectomy involves removal of the uterus with cervix without adjacent parametria. The uterine arteries are transected medial to the ureters at the level of the isthmus and the uterosacral ligaments are transected at the level of the cervix. Surgeons should pay special attention to make sure that the whole cervix is removed. As such, a maximum of 0.5 cm of vaginal cuff can be removed to ensure the complete removal of the cervix.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed adenocarcinoma, squamous, or adenosquamous cancer of the cervix. Diagnosis has been made by LEEP, cone or cervical biopsy and has been reviewed and confirmed by the local reference gynecological pathologist.
* Patient has been classified as low-risk early-stage cervical cancer. These patients include:

• FIGO Stage IA2 \[FIGO Annual Report, 2009\], defined as:

o evidence of disease by microscopy;
* for patients who underwent a LEEP or cone:

* histologic evidence of depth of stromal invasion \> 3.0 and ≤ 5.0 mm based on the local reference pathologist's measurement of the LEEP or cone specimen NB: the maximum depth of stromal invasion must be ≤ 10 mm.
* histologic evidence of lateral extension that is ≤ 7.0 mm based on the local reference pathologist's measurement of the LEEP or cone specimen; and
* negative margins (patients with positive margins are considered IB1, see below)
* for patients who underwent a cervical biopsy only:

* radiologic evidence of less than 50% stromal invasion based on pelvic MRI

• FIGO Stage IB1 \[FIGO Annual Report, 2009\] with favorable (low risk) features, defined as:
* measured stromal invasion and lateral extension that meet the criteria for IA2 (see above) but with positive margins;
* evidence of disease by clinical exam; lesion must clinically measure ≤ 20 mm
* evidence of disease by microscopy;
* for patients who underwent a LEEP or cone:

* histologic evidence of depth of stromal invasion between 5.1-10 mm and/or lateral extension between 7.1-20.0 mm based on the local reference pathologist's measurement of the LEEP or cone specimen
* for patients who underwent a cervical biopsy only:
* radiologic evidence of less than 50% stromal invasion based on pelvic MRI
* lateral extension ≤ 20 mm based on clinical exam or radiologic imaging.

In addition to above criteria on maximal stromal invasion of ≤ 10 mm, the lesion must be no larger than 20 mm in any dimension by any assessment method (MRI, clinical or histological exam). To ensure patients meet this criterion, investigators may need to sum the lesion measurements from biopsy and other methods that evaluate it in the same plane.

Patients are eligible irrespective of the presence or absence of lymph-vascular space involvement (LVSI).

* Physical examination, recto-vaginal examination and visualization of the cervix by speculum or colposcopic examination have been done after the initial diagnostic procedure (LEEP, cone or biopsy) and prior to randomization.
* Chest x-ray or CT scan of chest AND pelvic MRI\* done after initial diagnostic procedure (LEEP, cone or biopsy) and prior to randomization.

The CT should be a 16 slice (or higher) helical scanner. Oral and intravenous contrasts are preferred (unless there is a contraindication to the use of contrast) with scan obtained in the portal phase at a slice thickness of 5mm or lower Pelvic MRI should be performed on a 1.5 or 3 Tesla magnet with pelvic phased-array coils. The MR pulse sequences will consist of T1 gradient echo in the axial plane at 5 mm slice thickness and fast spin echo in the axial, sagittal, and coronal planes at 4 mm slice thickness. The short axis (perpendicular to the tumour's long axis) with a 3 mm slice thickness is required in the best plane to show the maximum thickness of stromal invasion. Use of an anti-peristaltic agent is mandatory while intravenous use of gadolinium or diffusion-weighted imaging (DWI) is optional.

\* Note: pelvic MRI is optional if the patient has stage IA2 disease and underwent a LEEP or cone.

* After consideration of a patient's medical history, physical examination and laboratory testing, patients must be suitable candidates for surgery as defined by the attending physician / investigator.
* Patients must have no desire to preserve fertility.
* Patients fluent in English or French must be willing to complete the Quality of Life Questionnaire. The baseline assessments must be completed within 6 weeks prior to randomization. Inability (illiteracy in English or French, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible. As additional GCIG groups join the study, more translations of some of the questionnaires may be added.

Patients fluent in English or French who reside in Canada and the United Kingdom must agree to participate in the economic evaluation component of this trial and complete the Health Economics Questionnaire. Similarly, patients fluent in English or French accrued from other GCIG groups who are participating in the economic evaluation must be willing to complete the Health Economics Questionnaires.

* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrolment in the trial to document their willingness to participate.
* Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
* Surgery is to be done within 20 weeks of initial diagnosis (NO EXCEPTIONS). The 20-week period includes time required for diagnosis, referral, diagnostic staging, randomization and scheduling of the surgical procedure.
* Patients must be ≥ 18 years old.

Exclusion Criteria

* Patients with FIGO 1A1 disease \[FIGO Annual Report, 2009\].
* History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours, Hodgkin's lymphoma or non-Hodgkin's lymphoma curatively treated with no evidence of disease for \> 5 years.
* Patients with evidence of lymph node metastasis on preoperative imaging or histology.
* Patients who have had or will receive neoadjuvant chemotherapy.
* Patients who are pregnant.
* Patients for whom adjuvant radiation and/or chemotherapy is planned.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Gynecologic Cancer Intergroup (GCIG)

OTHER

Sponsor Role collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role collaborator

Korean Gynecologic Oncology Group

OTHER

Sponsor Role collaborator

Dutch Gynaecological Oncology Group

OTHER

Sponsor Role collaborator

Cancer Trials Ireland

NETWORK

Sponsor Role collaborator

Arbeitsgemeinschaft Gynaekologische Onkologie Austria

OTHER

Sponsor Role collaborator

Belgian Gynaecological Oncology Group

OTHER

Sponsor Role collaborator

ARCAGY/ GINECO GROUP

OTHER

Sponsor Role collaborator

Institute of Cancer Research, United Kingdom

OTHER

Sponsor Role collaborator

Shanghai Cancer Centre

OTHER

Sponsor Role collaborator

P. Herzen Moscow Oncology Research Institute

OTHER_GOV

Sponsor Role collaborator

Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom Germany

OTHER

Sponsor Role collaborator

Institut Universitaire du Cancer de Toulouse

OTHER

Sponsor Role collaborator

Canadian Cancer Trials Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marie Plante

Role: STUDY_CHAIR

Canadian Cancer Trials Group

Gwenael Ferron

Role: STUDY_CHAIR

France-GINECO

Jae-Weon Kim

Role: STUDY_CHAIR

Korean Gynecology Oncology Group

Christian Marth

Role: STUDY_CHAIR

Arbeitsgemeinschaft Gynaekologische Onkologie Austria

John Tidy

Role: STUDY_CHAIR

Institute of Cancer Research, United Kingdom

Noreen Gleeson

Role: STUDY_CHAIR

Ireland Co-operative Oncology Research Group

Frederic Goffin

Role: STUDY_CHAIR

Belgian Gynaecological Oncology Group

Cor de Kroon

Role: STUDY_CHAIR

The Dutch Gynecological Oncology Group (DGOG)

Xiaohua Wu

Role: STUDY_CHAIR

Fudan University

Sven Mahner

Role: STUDY_CHAIR

AGO Germany

Brynhildur Eyjolfsdottir

Role: STUDY_CHAIR

Oslo University Hospital

Alexey Shevchuk

Role: STUDY_CHAIR

Hertzen Institute, Moscow

Locations

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Barmherzige Brueder Graz

Graz, , Austria

Site Status

Medical University of Graz

Graz, , Austria

Site Status

Medical University of Innsbruck

Innsbruck, , Austria

Site Status

LKH Leoben

Leoben, , Austria

Site Status

Landes- Frauen- und Kinderklinik Linz

Linz, , Austria

Site Status

LKH Salzburg

Salzburg, , Austria

Site Status

Medical University of Vienna

Vienna, , Austria

Site Status

UZ Leuven

Leuven, Vlaams-Brabant, Belgium

Site Status

CHR de la Citadelle liege

Liège, , Belgium

Site Status

CHU Sart Tilman Liege

Liège, , Belgium

Site Status

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

Clinical Research Unit at Vancouver Coastal

Vancouver, British Columbia, Canada

Site Status

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status

QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

Site Status

Royal Victoria Regional Health Centre

Barrie, Ontario, Canada

Site Status

London Regional Cancer Program

London, Ontario, Canada

Site Status

Trillium Health Partners - Credit Valley Hospital

Mississauga, Ontario, Canada

Site Status

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Site Status

University Health Network

Toronto, Ontario, Canada

Site Status

Greenfield Park, Quebec, Canada

Site Status

CIUSSS de l'Est-de-I'lle-de-Montreal

Montreal, Quebec, Canada

Site Status

CHUM-Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada

Site Status

The Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Québec, Quebec, Canada

Site Status

CIUSSS de l'Estrie - Centre hospitalier

Sherbrooke, Quebec, Canada

Site Status

Shanghai Cancer Center

Shanghai, , China

Site Status

CHU Amiens

Amiens, , France

Site Status

Institut Bergonie Bordeaux

Bordeaux, , France

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CHRU de Brest

Brest, , France

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CHU de Chambery

Chambéry, , France

Site Status

CHU de Clermont-Ferrand

Clermont-Ferrand, , France

Site Status

Centre Jean Perrin - Clermont-Ferrand

Clermont-Ferrand, , France

Site Status

Centre Georges Francois Leclerc - Dijon

Dijon, , France

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CHU de Dijon

Dijon, , France

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Centre Oscar Lambret - Lille

Lille, , France

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CHRU de Lille

Lille, , France

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CHU Limoges

Limoges, , France

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Hospices Civils de Lyon

Lyon, , France

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Centre Leon Berard - Lyon

Lyon, , France

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Institut Paoli Calmettes - Marseille

Marseille, , France

Site Status

Institut Regional du Cancer de Montpellier

Montpellier, , France

Site Status

Institut Arnault Tzank - Mougins

Mougins, , France

Site Status

CHU de Nice

Nice, , France

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CHU de Nimes

Nîmes, , France

Site Status

Hopital Europeen Georges Pompidou - Paris

Paris, , France

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CHU de Reims

Reims, , France

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CHU de Rennes

Rennes, , France

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Clinique Mutualiste de la Sagesse - Rennes

Rennes, , France

Site Status

Clinique Mathilde - Rouen

Rouen, , France

Site Status

ICO - Rene Gauducheau

Saint-Herblain, , France

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CHU de Strasbourg

Strasbourg, , France

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CHU de Bordeaux

Talence, , France

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Institut Claudius Regaud - Toulouse

Toulouse, , France

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CHRU de Tours

Tours, , France

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Hochtaunus-Kliniken gGmbH

Bad Homburg, , Germany

Site Status

DRK Kliniken Berlin Koepenick

Berlin, , Germany

Site Status

DRK Klinikum Berlin Westend

Berlin, , Germany

Site Status

Martin-Luther-Krankenhaus Berlin

Berlin, , Germany

Site Status

GYNAEKOLOGICUM Bremen

Bremen, , Germany

Site Status

Universitaetsfrauenklinik Duesseldorf

Düsseldorf, , Germany

Site Status

Kaiserswerther Diakonie - Florence-Nightingale-Krankenhaus

Düsseldorf, , Germany

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Kliniken Essen Mitte

Essen, , Germany

Site Status

Universitaetsfrauenklinik Freiburg

Freiburg im Breisgau, , Germany

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Universitaetsfrauenklinik Greifswald

Greifswald, , Germany

Site Status

Universitaetsklinikum Hamburg - Eppendorf

Hamburg, , Germany

Site Status

Agaplesion Diakonieklinikum Hamburg

Hamburg, , Germany

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Medizinische Hochschule Hannover

Hanover, , Germany

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Universitaetsklinikum des Saarlandes

Homburg-Saar, , Germany

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Universitaetsfrauenklinik Jena

Jena, , Germany

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Universitaetsfrauenklinik Luebeck

Lübeck, , Germany

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Universitaetsfrauenklinik Mainz

Mainz, , Germany

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Klinikum der Universitaet Muenchen - LMU Campus Grosshadern

München, , Germany

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Universitaetsfrauenklinik Tuebingen

Tübingen, , Germany

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Universitaetsfrauenklinik Ulm

Ulm, , Germany

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Marien-Hospital Witten

Witten, , Germany

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St James Hospital

Dublin, Leinster, Ireland

Site Status

LUMC

Leiden, , Netherlands

Site Status

Erasmus MC

Rotterdam, , Netherlands

Site Status

Oslo University Hospital

Oslo, Postboks 4953 Nydalen, Norway

Site Status

Hertzen Moscow Scientific Research

Moscow, , Russia

Site Status

Royal Cornwall Hospital

Truro, Cornwall, United Kingdom

Site Status

Southend University Hospital

Westcliff-on-Sea, Essex, United Kingdom

Site Status

East Kent Hospitals University NHS Foundation Trust

Canterbury, Ethelbert Road, United Kingdom

Site Status

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, Glossop Road, United Kingdom

Site Status

South Tees Hospitals NHS Foundation Trust

Middlesbrough, Marton Road, United Kingdom

Site Status

Queen Alexandra Hospital

Portsmouth, , United Kingdom

Site Status

Countries

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Austria Belgium Canada China France Germany Ireland Netherlands Norway Russia United Kingdom

References

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Plante M, Kwon JS, Ferguson S, Samouelian V, Ferron G, Maulard A, de Kroon C, Van Driel W, Tidy J, Williamson K, Mahner S, Kommoss S, Goffin F, Tamussino K, Eyjolfsdottir B, Kim JW, Gleeson N, Brotto L, Tu D, Shepherd LE; CX.5 SHAPE investigators; CX.5 SHAPE Investigators. Simple versus Radical Hysterectomy in Women with Low-Risk Cervical Cancer. N Engl J Med. 2024 Feb 29;390(9):819-829. doi: 10.1056/NEJMoa2308900.

Reference Type RESULT
PMID: 38416430 (View on PubMed)

Kwon JS, McTaggart-Cowan H, Ferguson SE, Samouelian V, Lambaudie E, Guyon F, Tidy J, Williamson K, Gleeson N, de Kroon C, van Driel W, Mahner S, Hanker L, Goffin F, Berger R, Eyjolfsdottir B, Kim JW, Brotto LA, Pataky R, Yeung SST, Chan KKW, Cheung MC, Ubi J, Tu D, Shepherd LE, Plante M. Cost-effectiveness analysis of simple hysterectomy compared to radical hysterectomy for early cervical cancer: analysis from the GCIG/CCTG CX.5/SHAPE trial. J Gynecol Oncol. 2024 Nov;35(6):e117. doi: 10.3802/jgo.2024.35.e117. Epub 2024 Oct 18.

Reference Type DERIVED
PMID: 39453395 (View on PubMed)

Ferguson SE, Brotto LA, Kwon J, Samouelian V, Ferron G, Maulard A, Kroon C, Driel WV, Tidy J, Williamson K, Mahner S, Kommoss S, Goffin F, Tamussino K, Eyjolfsdottir B, Kim JW, Gleeson N, Tu D, Shepherd L, Plante M. Sexual Health and Quality of Life in Patients With Low-Risk Early-Stage Cervical Cancer: Results From GCIG/CCTG CX.5/SHAPE Trial Comparing Simple Versus Radical Hysterectomy. J Clin Oncol. 2025 Jan 10;43(2):167-179. doi: 10.1200/JCO.24.00440. Epub 2024 Oct 1.

Reference Type DERIVED
PMID: 39353164 (View on PubMed)

Boisen M, Guido R. Emerging Treatment Options for Cervical Dysplasia and Early Cervical Cancer. Clin Obstet Gynecol. 2023 Sep 1;66(3):500-515. doi: 10.1097/GRF.0000000000000790. Epub 2023 Jul 25.

Reference Type DERIVED
PMID: 37650664 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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CX5

Identifier Type: -

Identifier Source: org_study_id