PORTEC-4a, een onderzoek naar de waarde van een individueel moleculaire risicoprofiel om de nabehandeling na operatie voor vroeg stadium baarmoederkanker (endometriumcarcinoom) te bepalen.

Current standard postoperative treatment for women with early stage, high-intermediat risk endometrial cancer is vaginal brachytherapy, which provides excellent local control with minimal side effects. However, as there is no difference in survival, as 7-8 women have to be treated to prevent 1 vaginal recurrence, and as patients with local recurrence can be effectively salvaged, the question is if this is overtreatment and more effective prediction of the risk of relapse can save many women vaginal brachytherapy and reduce health care costs.

In recent years, the genomic characterisation of endometrial cancer as published by The Cancer Genome Atlas and subsequent independent studies of molecular risk factors such as POLE, L1CAM, MSI, p53 have provided insight into the mutations underlying endometrial cancer development and progression, and have shown strong prognostic impact. In the translational research of PORTEC1- and 2 trials (900 pts) an integrated molecular risk profile has been determined which subclassifies patients with early stage, high-intermiadate risk endometrial cancer as favorable, intermediate or unfavorable, with significantly better prognostic power than the clinicopathologic risk assessment. In the PORTEC-4a trial, this integrated molecular risk profile will be used to evaluate the patient's individual risk and determine adjuvant treatment (favorable: observation; intermediate: vaginal brachytherapy; unfavorable: extermal beam radiotherapy) and compared to standard indication for vagial brachytherapy for all patiente with early stage, high-intermediate risk features.

Objectives and design:

Patient with early stage, high-intermediate risk endometrial carcinoma 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).

The first cohort of 50 patients were included in a pilot phase of the study, which tested the acceptability and logistics of this multicentre study. Results were positive, and the trial has continued and will include 550 evaluable patients, with international participating groups.

Molecular risk profile-based recommendations for adjuvant treatment will, in comparison to standard vaginal brachytherapy, lead to similar vaginal recurrence and recurrence-free survival in patients with high-intermediate risk endometrial carcinoma,while sparing about 50% of women postoperative vaginal brachytherapy and saving health care costs

5-year rates of vaginal control, survival, adverse events, quality of life, health care costs

Evaluation of outcomes and quality of life at 6 month intervals
Long-term outcomes at 7 years after randomisation

Publications:

Wortman BG, et al: Molecular-integrated risk profile to determine adjuvant radiotherapy in endometrial cancer: Evaluation of the pilot phase of the PORTEC-4a trial.Gynecol Oncol. 2018 Oct;151(1):69-75. doi: 10.1016/j.ygyno.2018.07.020. Epub 2018 Aug 3

Van den Heerik ASVM et al: PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer. Int J Gynecol Cancer. 2020 Dec;30(12):2002-2007. doi: 10.1136/ijgc-2020-001929. Epub 2020 Oct 12. PMID: 33046573

Wortman BG, et al: Brachytherapy quality assurance in the PORTEC-4a trial for molecular-integrated risk profile guided adjuvant treatment of endometrial cancer. Radiother Oncol. 2021 Feb;155:160-166. doi: 10.1016/j.radonc.2020.10.038. Epub 2020 Nov 5

Arm 1 (standard): vaginal brachytherapy

Arm 2 (molecular profile based recommendations for adjuvant treatment): observation, vaginal brachytherapy or external beam radiotherapy