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
- Histologically confirmed adenocarcinoma, squamous, or adenosquamous cancer of the
cervix diagnosed within 12 weeks prior to randomization. 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
- FIGO Stage IA2 [FIGO Annual Report, 2009], defined as:
- evidence of disease by microscopy;
1. for patients who underwent a LEEP or cone.
- histologic evidence of depth of stromal invasion between 3.0-5.0
mm based on the local reference pathologist's measurement of the
LEEP or cone specimen.
- histologic evidence of lateral extension that is not greater than
7.0 mm based on the local reference pathologist's measurement of
the LEEP or cone specimen.
- negative margins.
2. for patients who underwent a cervical biopsy only:
- radiologic evidence of less than 50% stromal invasion based on
- FIGO Stage IB1 [FIGO Annual Report, 2009] with favorable (low risk) features,
- a clinically visible lesion or a microscopically diagnosed lesion measuring
> 5 mm depth of invasion or > 7 mm in lateral extension;
- histologic evidence of less than 10mm stromal invasion based on the local
reference pathologist's measurement of the LEEP or cone specimen Note: this
criterion will not apply to patients who underwent a cervical biopsy only;
- Radiologic evidence of maximum dimension of ≤ 20 mm as seen by pelvic MRI;
- Radiologic evidence of less than 50% stromal invasion based on pelvic MRI.
Note: Patients are eligible irrespective of the presence or absence of
lymph-vascular space involvement (LVSI).
- The histologic grade of cervical cancer must be 1, 2, 3 or not assessable [FIGO
Annual Report, 2009].
- 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. Staging criteria
described in 5.1.2 must be satisfied based on these examinations.
- 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 required (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 not required 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, French or Spanish must be willing to complete the Quality
of Life Questionnaire and the Sexual Health Questionnaire. The baseline assessments
must be completed within 6 weeks prior to randomization. Inability (illiteracy in
English, French or Spanish, 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
enrollment 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 8 weeks of randomization.
- Patients must be ≥ 18 years old.
- 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.