PORTEC-4a: Randomised trial of standard or molecular profile-based recommendation for radiotherapy after surgery for women with early stage endometrial cancer

Plain English Summary

Background and study aims
For women with early stage endometrial (womb) cancer, current standard treatment is surgery (removal of the uterus and ovaries) followed by vaginal brachytherapy. Vaginal brachytherapy is a type of radiotherapy where a special applicator is placed in the vagina in which a small pellet of radioactive material is placed to give radiation treatment to the inner part of the vagina. With brachytherapy, the risk of local recurrence (that is, the tumour coming back) is very low and there are very few side effects. However, many women are treated with vaginal brachytherapy, while only few really need this. About 10 women have to be treated to prevent 1 vaginal recurrence. If local recurrence is found, this can be effectively treated at that time. Therefore, treating all women considered to be at risk seems unnecessary. If a better way of predicting which women are likely to suffer a relapse (vaginal recurrence) can be developed then not so many women have to undergo vaginal brachytherapy . This, in turn, will reduce health care costs. In recent years, scientific studies have shown that there are specific alterations in the genes of tumor cells which enable recurrence and the spread of cancer. For endometrial cancer, a better individual risk prediction has been obtained by combining known risk factors with individual alterations in the genes of their tumor. By determining this risk profile on the tumor tissue which has been removed at surgery, a better recommendation can be obtained as to what treatment should be performed, including whether or not vaginal brachytherapy is required

Objectives and design:
In the PORTEC-4a trial, the standard vaginal brachytherapy (standard treatment) will be compared to the use of the individual risk profile to determine adjuvant treatment (favorable: observation; intermediate: vaginal brachytherapy; unfavorable: extermal beam radiotherapy). The aim is to evaluate if the use of the individual risk profile saves many women unnecessary vaginal brachytherapy with similarly high recurrence-free survival and local control, and reduced health costs.
This is a randomised trial, and eligible and consenting women will be randomly assigned (1:2) to vaginal brachytherapy (standard arm) or molecular profile-based recommendations for either observation, vaginal brachytherapy or external beam radiotherapy (investigational arm).

Who can participate?
Women of any age (above 18) who have had surgery (removal of uterus and ovaries) for early stage endometrial cancer.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in group 1 (control group) have
vaginal brachytherapy as usual. Those in group 2 (intervention group) either have no further treatment after surgery, vaginal brachytherapy or external beam radiation therapy, depending upon their molecular profile (that is, the type of alterations in the genes of the tumor cells). All participants are then followed up for at least 5 years to check for recurrence of the tumor, quality of life and any side effects.

What are the possible benefits and risks of participating?
Possible benefits include being spared from further treatment after surgery and have a better understanding what the individual risk of recurrence is.

Where is the study run from?
Lead center is Leiden University Medical Center in the Netherlands. Participating centres are found in all regions of the Netherlands.

When is study starting and how long is it expected to run for?
June 2016 to December 2028

Who is funding the study?
Dutch Cancer Society.

Who is the main contact?
Professor Carien Creutzberg

Study website

Contact information

Prof Carien Creutzberg
Scientific

Leiden University Medical Centre
Dept of Radiation Oncology, K1-P
Albinusdreef 2
Leiden
2333 ZA
Netherlands

ORCID ID	0000-0002-7008-4321
Phone	+31.71.526.5120
Email	c.l.creutzberg@lumc.nl

Dr Anne-Sophie V.M. van den Heerik
Scientific

Leiden University Medical Center, Dept of Radiation Oncology
Albinusdreef 2
Leiden
2333 ZA
Netherlands

ORCID ID	0000-0001-6403-0143
Phone	+31 (0)71 526 5539
Email	a.v.m.van_den_heerik@lumc.nl

Study information

Eligibility

Locations

Countries of recruitment

• Austria
• Belgium
• Czech Republic
• France
• Germany
• Ireland
• Netherlands
• Switzerland

Study participating centres

Sponsor information

Leiden University Medical Center
Hospital/treatment centre

Albinusdreef 2
Leiden
2333 ZA
Netherlands

Website	www.lumc.nl
"ROR"	https://ror.org/05xvt9f17

Funders

Funder type

Charity

Results and Publications

Study outputs

Editorial Notes

11/12/2024: A contact confirmed that the study remains ongoing and the dates are correct.
13/12/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2021 to 24/12/2021.
2. The intention to publish date was changed from 31/12/2023 to 31/12/2024.
3. The data sharing statement was added.
17/08/2021: The following changes were made to the trial record:
1. The study contact details and exclusion criteria were updated.
2. The following trial participating centres were added: University Hospital Gent, University Hospital Tubingen, Rotkreuzklinikum München, Kliniken Essen-Mitte, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Kaiserswerther Diakonie Düsseldorf, Universitatsklinikum Heidelberg, Sankt Gertrauden Krankenhaus Berlin, Kantonsspital Frauenklinik Lucerne, Saint Luke’s Radiation Oncology Network (SLRON), Dublin, St James’s Hospital (SJH), Dublin, Czech republic (group: CEEGOG), University Hospital Prague, Institut Gustave-Roussy, Paris, Hôpital Européen Georges-Pompidou, Paris, Hôpital Tenon, Paris, Medical University, Vienna.
3. The following trial participating centres were removed: Medical Spectrum Twente, Enschede and Radiotherapy Group, Deventer.
4. The target number of participants was changed from 500 to 550.
5. Link to participant information sheet added.
6. Germany, Belgium, Czech Republic, Ireland, Switzerland, Austria and France were added to the countries of recruitment and Australia, New Zealand and the UK were removed.
7. Publication references added.
01/12/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2020 to 31/12/2021.
2. The overall trial end date was changed from 01/06/2025 to 31/12/2028.
3. The intention to publish date was changed from 31/12/2021 to 31/12/2023.
4. IPD sharing statement added.
09/07/2020: The trial contact details have been made publicly visible.
14/02/2020: ClinicalTrials.gov number added.
12/11/2018: Publication reference added.
28/06/2016: Internal review