Endometrial Cancer Stage I, Endometrial Cancer Stage II
Conditions
Keywords
Radiotherapy, Vaginal brachytherapy, Molecular risk factors
Brief summary
This is prospective, multicenter, randomised phase III trial among women with endometrial cancer with high-intermediate risk features to investigate the role of an integrated clinicopathological and molecular risk profile to determine if participants should receive no adjuvant therapy, vaginal brachytherapy or external beam radiotherapy based on a favourable, intermediate or unfavourable profile as compared to standard adjuvant vaginal brachytherapy.
Detailed description
Adjuvant therapy for women with endometrial cancer has increasingly been tailored to prognostic factors to prevent overtreatment and select those women for adjuvant treatment who will have a clinically relevant reduction of the risk of relapse by the adjuvant treatment. Risk profiles have traditionally been based on clinicopathological factors such as age, stage, grade, LVSI and depth of invasion. Newer, both molecular-genetic (the cancer genome atlas subgroups) or immunohistochemistry-based (L1-CAM) risk factors have become available which are strongly related to outcomes and risk of cancer spread. In a comprehensive analysis of the PORTEC-1 and-2 biobank an integrated clinicopathological and molecular risk profile was determined which separated the current high-intermediate risk group of endometrial cancer in 3 separate groups (favourable, intermediate or unfavourable) with clearly separated outcomes, which is now prospectively tested in the clinic to determine adjuvant treatment. This is the first randomised trial using the molecular risk factors to assign adjuvant treatment for women with stage I-II high-intermediate risk endometrial cancer.
Interventions
RADIATIONVaginal brachytherapy
Internal radiation of the vaginal vault using a vaginal cylinder, 21 Gy in 3 out-patient sessions over 2 weeks
RADIATIONExternal beam radiotherapy
External beam pelvic radiotherapy on a linear accelerator, 48.6 Gy in 27 out-patients sessions over 5.5 weeks
OTHERObservation
No radiation therapy, but active follow-up and quality of life questionnaires as in the groups who have adjuvant treatment
Sponsors
Dutch Cancer Society
Comprehensive Cancer Centre The Netherlands
Leiden University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Evaluation of outcomes is done without information on randomised arm
Intervention model description
2:1 randomisation to adjuvant treatment assignment based on the integrated molecular risk profile or standard adjuvant vaginal brachytherapy
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed endometrioid type endometrial carcinoma, International Federation of Gynecology and Obstetrics (FIGO) 2009 stage I, with one of the following combinations of stage, grade, age, and lymph-vascular space invasion (LVSI): 1. Stage IA, grade 3 (any age, with or without LVSI) 2. Stage IB, grade 1 or 2 and age \>60 years 3. Stage IB, grade 1-2 with documented LVSI 4. Stage IB, grade 3 without LVSI 5. Stage II (microscopic), grade 1 * World Health Organization (WHO)-performance status 0-2 * Written informed consent
Exclusion criteria
* Any other stage and type of endometrial carcinoma * Histological types serous carcinoma or clear cell carcinoma (at least 10% if mixed type), or undifferentiated or neuroendocrine carcinoma * Uterine sarcoma (including carcinosarcoma) * Previous malignancy (except for non-melanomatous skin cancer) \< 5 yrs * Previous pelvic radiotherapy * Expected interval between the operation and start of radiotherapy exceeding 8 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vaginal recurrence | 5 years | Total vaginal recurrence and vaginal recurrence as first failure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 5 years | Treatment-related symptoms according to CTCAE v 4.0 |
| Health-related cancer-specific quality of life | 5 years | Cancer-specific quality of life (European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQC-30) - clinically relevant changes on QLQC30 functioning scales, general quality of life and general cancer symptoms |
| Endometrial cancer-related symptoms and quality of life | 5 years | Endometrial cancer-related specific symptoms (EORTC EN24 module)- clinically relevant changes on these scales (quite a bit/very much vs no or mild symptoms) |
| Relapse-free survival | 5 years | Relapse-free survival (survival without relapse) |
| Survival | 5 years | Overall survival (all-cause death) |
| Pelvic recurrence (total) | 5 years | Total pelvic recurrences |
| Pelvic recurrence as first failure | 5 years | Pelvic recurrence as first failure |
| Distant recurrence (total) | 5 years | Total distant recurrences |
| Distant recurrence as first failure | 5 years | Distant recurrence as first failure |
| Endometrial cancer related health care costs | 5 years | All hospital based health care costs used with primary treatment or during followup for treatment of adverse events and/or treatment for relapse |
| 5-year vaginal control including treatment for relapse | 5 years | Long-term local control including salvage treatment for local relapse |
Other
| Measure | Time frame | Description |
|---|---|---|
| Recurrence (vaginal and total) per risk profile | 5 years | Vaginal, pelvic and distant relapse split by risk profile and compared between the 2 arms |
Countries
Austria, Belgium, Czechia, France, Germany, Ireland, Netherlands, Switzerland
Outcome results
None listed