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

A Randomized Phase III Trial Comparing Radical Hysterectomy and Pelvic Node Dissection vs Simple Hysterectomy and Pelvic Node Dissection in Patients With Low-Risk Early Stage Cervical Cancer (SHAPE)

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.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer
• Intervention / Treatment: Procedure: Radical Hysterectomy + pelvic lymph node dissection; Procedure: Simple hysterectomy + pelvic lymph node dissection

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 700
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Medical University of Graz
  • Graz, Austria, 8020
    • Barmherzige Brueder Graz
  • Innsbruck, Austria, 6020
    • Medical University of Innsbruck
  • Leoben, Austria, 8700
    • LKH Leoben
  • Linz, Austria, 4020
    • Landes- Frauen- und Kinderklinik Linz
  • Salzburg, Austria, 5020
    • LKH Salzburg
  • Vienna, Austria, 1090
    • Medical University of Vienna
• Belgium
  • Liege, Belgium, 4000
    • CHU Sart Tilman Liege
  • Liege, Belgium, 4000
    • CHR de la Citadelle liege
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • UZ Leuven
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Clinical Research Unit at Vancouver Coastal
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • QEII Health Sciences Centre
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Regional Health Centre
    • London, Ontario, Canada, N6A 5W9
      • London Regional Cancer Program
    • Mississauga, Ontario, Canada, L5M 2N1
      • Trillium Health Partners - Credit Valley Hospital
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Research Institute
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
    • Montreal, Quebec, Canada, H2X 3E4
      • CHUM-Centre Hospitalier de l'Universite de Montreal
    • Montreal, Quebec, Canada, H3T 1E2
      • The Jewish General Hospital
    • Montreal, Quebec, Canada, H1T 2M4
      • CIUSSS de l'Est-de-I'lle-de-Montreal
    • Quebec City, Quebec, Canada, G1R 2J6
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • CIUSSS de l'Estrie - Centre hospitalier
• China
  • Shanghai, China, 200032
    • Shanghai Cancer center
• France
  • Amiens, France, 80054
    • CHU Amiens
  • Bordeaux, France, 33076
    • Institut Bergonié Bordeaux
  • Brest, France, 29609
    • CHRU de Brest
  • Chambery, France, 73011
    • CHU de Chambery
  • Clermont Ferrand, France, 63011
    • Centre Jean PERRIN - Clermont-Ferrand
  • Clermont-Ferrand, France, 63003
    • CHU de Clermont-Ferrand
  • Dijon, France, 21079
    • Chu de Dijon
  • Dijon, France, 21079
    • Centre Georges Francois Leclerc - Dijon
  • Lille, France, 59037
    • CHRU de Lille
  • Lille, France, 59000
    • Centre Oscar Lambret - Lille
  • Limoges, France, 87042
    • CHU Limoges
  • Lyon, France, 69229
    • Hospices Civils de Lyon
  • Lyon, France, 69373
    • Centre Léon Bérard - Lyon
  • Marseille, France, 13273
    • Institut Paoli Calmettes - Marseille
  • Montpellier, France, 34298
    • Institut Regional Du Cancer de Montpellier
  • Mougins, France, 06254
    • Institut Arnault Tzank - Mougins
  • Nice, France, 06003
    • CHU de Nice
  • Nimes, France, 30029
    • CHU de Nîmes
  • Paris, France, 75015
    • HOPITAL EUROPEEN GEORGES POMPIDOU - Paris
  • Reims, France, 51092
    • Chu de Reims
  • Rennes, France, 35033
    • CHU de Rennes
  • Rennes, France, 35043
    • Clinique Mutualiste de la Sagesse - Rennes
  • Rouen, France, 76175
    • Clinique Mathilde - Rouen
  • Saint-Herblain, France, 44805
    • ICO - Rene Gauducheau
  • Strasbourg, France, 67091
    • CHU de Strasbourg
  • Talence, France, 33404
    • CHU de Bordeaux
  • Toulouse, France, 31059
    • Institut Claudius REGAUD - Toulouse
  • Tours, France, 37044
    • Chru De Tours
• Germany
  • Bad Homburg, Germany, 61352
    • Hochtaunus-Kliniken gGmbH
  • Berlin, Germany, 12559
    • DRK Kliniken Berlin Koepenick
  • Berlin, Germany, 14050
    • DRK Klinikum Berlin Westend
  • Berlin, Germany, 14193
    • Martin-Luther-Krankenhaus Berlin
  • Bremen, Germany, 28211
    • GYNAEKOLOGICUM Bremen
  • Duesseldorf, Germany, 40225
    • Universitaetsfrauenklinik Duesseldorf
  • Duesseldorf, Germany, 40489
    • Kaiserswerther Diakonie - Florence-Nightingale-Krankenhaus
  • Essen, Germany, 45136
    • Kliniken Essen Mitte
  • Freiburg, Germany, 79106
    • Universitaetsfrauenklinik Freiburg
  • Greifswald, Germany, 17475
    • Universitaetsfrauenklinik Greifswald
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg - Eppendorf
  • Hamburg, Germany, 20259
    • Agaplesion Diakonieklinikum Hamburg
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Homburg-Saar, Germany, 66421
    • Universitaetsklinikum des Saarlandes
  • Jena, Germany, 07747
    • Universitaetsfrauenklinik Jena
  • Luebeck, Germany, 23538
    • Universitaetsfrauenklinik Luebeck
  • Mainz, Germany, 55131
    • Universitaetsfrauenklinik Mainz
  • Muenchen, Germany, 81377
    • Klinikum der Universitaet Muenchen - LMU Campus Grosshadern
  • Tuebingen, Germany, 72076
    • Universitaetsfrauenklinik Tuebingen
  • Ulm, Germany, 89075
    • Universitaetsfrauenklinik Ulm
  • Witten, Germany, 58452
    • Marien-Hospital Witten
• Ireland
  • Leinster
    • Dublin, Leinster, Ireland, Dublin 8
      • St James Hospital
• Netherlands
  • Leiden, Netherlands, 2300 RC
    • LUMC
  • Rotterdam, Netherlands, 3000CA
    • Erasmus MC
• Norway
  • Postboks 4953 Nydalen
    • Oslo, Postboks 4953 Nydalen, Norway, 0424
      • Oslo University Hospital
• Russian Federation
  • Moscow, Russian Federation
    • Hertzen Moscow Scientific Research
• United Kingdom
  • Portsmouth, United Kingdom, PO6 3LY
    • Queen Alexandra Hospital
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Royal Cornwall Hospital
  • Essex
    • Westcliff-on-Sea, Essex, United Kingdom, SS0 0RY
      • Southend University Hospital
  • Ethelbert Road
    • Canterbury, Ethelbert Road, United Kingdom, CT1 3NG
      • East Kent Hospitals University NHS Foundation Trust
  • Glossop Road
    • Sheffield, Glossop Road, United Kingdom, S10 2TJ
      • Sheffield Teaching Hospitals NHS Foundation Trust
  • Marton Road
    • Middlesbrough, Marton Road, United Kingdom, TS4 3BW
      • South Tees Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Radical Hysterectomy	Procedure: 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.
Experimental: Simple Hysterectomy	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pelvic Recurrence Rate at 3 Years	Pelvic recurrence rate at 3 years was estimated by 1-the Kaplan-Meier estimate for the probability of pelvic relapse free survival (PRFS) at 3 years. PRFS was defined as the time from randomization to the time when a recurrence within the pelvic field was first documented. Patients who had a relapse outside of the pelvic field documented or died before the documentation of a pelvic relapse were censored at the time of first documented extra-pelvic relapse or death. The pelvic relapse free survival of patients who were alive without any relapse at the time of final analysis was censored at the last known alive.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pelvic Relapse-free Survival	It was defined as the time from randomization to the time when a recurrence within the pelvic field was first documented. Patients who had a relapse outside of the pelvic field documented or died before the documentation of a pelvic relapse were censored at the time of first documented extra-pelvic relapse or death. The pelvic relapse free survival of patients who were alive without any relapse at the time of final analysis was censored at the last known alive. 3 year pelvic relapse-free survival was estimated by Kaplan-Meier method.	3 years
Extra-pelvic Relapse-free Survival	It was defined as the time from randomization to the documented reappearance of disease provided that this recurrence is outside of pelvic. Patients who relapsed in pelvic field were censored at the time of first documented pelvic relapse. Patients who died before any relapse or alive without recurrence were censored at the date of death or last known alive date. 3 year extra-pelvic relapse-free survival was estimated by Kaplan-Meier method.	3 years
Relapse-free Survival	It was defined as the time from randomization to the first time when either a pelvic or extra-pelvic recurrence was documented. Patients who died before any recurrence or alive without recurrence were censored at the date of death or last known alive date. 3 year relapse-free survival was estimated by Kaplan-Meier method.	3 years
Overall Survival	It was defined as the time from randomization until death from any cause. The living patients were censored at the date of last known alive. 3 year overall survival was estimated by Kaplan-Meier method.	3 years

Collaborators and Investigators

• Sponsor: Canadian Cancer Trials Group
• Collaborators: Canadian Institutes of Health Research (CIHR); Institute of Cancer Research, United Kingdom; ARCAGY/ GINECO GROUP; Belgian Gynaecological Oncology Group; Korean Gynecologic Oncology Group; Cancer Trials Ireland; Arbeitsgemeinschaft Gynaekologische Onkologie Austria; Gynecologic Cancer Intergroup (GCIG); Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom Germany; Dutch Gynaecological Oncology Group; P. Herzen Moscow Oncology Research Institute; Shanghai Cancer Centre; Institut Universitaire du Cancer de Toulouse
• Investigators: Study Chair: Marie Plante, Canadian Cancer Trials Group; Study Chair: Gwenael Ferron, France-GINECO; Study Chair: Jae-Weon Kim, Korean Gynecology Oncology Group; Study Chair: Christian Marth, Arbeitsgemeinschaft Gynaekologische Onkologie Austria; Study Chair: John Tidy, Institute of Cancer Research, United Kingdom; Study Chair: Noreen Gleeson, Ireland Co-operative Oncology Research Group; Study Chair: Frederic Goffin, Belgian Gynaecological Oncology Group; Study Chair: Cor de Kroon, The Dutch Gynecological Oncology Group (DGOG); Study Chair: Xiaohua Wu, Fudan University; Study Chair: Sven Mahner, AGO Germany; Study Chair: Brynhildur Eyjolfsdottir, Oslo University Hospital; Study Chair: Alexey Shevchuk, Hertzen Institute, Moscow

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2012
• Primary Completion (Actual): March 11, 2023
• Study Completion (Actual): November 4, 2024

Study Registration Dates

• First Submitted: August 3, 2012
• First Submitted That Met QC Criteria: August 6, 2012
• First Posted (Estimated): August 7, 2012

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 21, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Uterine Cervical Neoplasms
• Other Study ID Numbers: CX5

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No