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The PORTEC-4a trial is the first study worldwide that introduced molecular factors in decision making on adjuvant treatment for women with high-intermediate risk endometrial cancer (HIR-EC). For patients randomised to the intervention arm, adjuvant treatment was based upon a molecular-integrated risk profile.  Here we report on the feasibility of determining the molecular-integrated risk profile and starting adjuvant therapy within a clinically acceptable time frame after surgery.

Women with complete surgical resection of HIR-EC were eligible. Patients were randomized (2:1) between individualized treatment based upon the molecular-integrated risk profile and standard vaginal brachytherapy (VBT). In patients with a favourable profile, adjuvant treatment was omitted; in those with an intermediate profile, VBT was recommended, and the small group with an unfavourable profile received pelvic radiotherapy. After randomisation, histopathological slides and representative tumour block were obtained by pathology laboratories which had been validated for review and determination of the molecular-integrated risk profile. Histopathological, immunohistochemical and molecular analyses were performed, after which risk groups assignment was done and adjuvant therapy could be initiated, figure 1. Accrual completed in December 2021 and final results are expected in 2024.

Between 2016 and 2021, 569 patients were enrolled of whom 361 evaluable patients were allocated to the intervention arm. Twelve pathology laboratories in 8 European countries were validated during the conducted of the trial. Of 284 patients the molecular-integrated risk profile was determined at the LUMC department of Pathology and 77 at laboratories elsewhere. Average time between randomisation and result of the risk profile was 2 weeks (range 0 – 6 weeks) for LUMC and 3 weeks (0 – 12 weeks) for other laboratories. For 48.5% of participants pathology review took longer than 2 weeks, of which 1.1% more than 6 weeks. Median time between surgery and start of adjuvant treatment was 7 weeks (0 – 13 weeks); this was 7 weeks (5 – 12 weeks) for patients receiving VBT and 8 weeks (5 – 13 weeks) for pelvic radiotherapy. Less than 10% of patients started adjuvant treatment more than 9 weeks after surgery. Only in 2 (0.5%) cases determination of the risk profile failed due to technical issues; these patients received VBT according to protocol.

Determination of the molecular-integrated risk profile for participants of the PORTEC-4a trial was proven to be feasible within a clinically acceptable time frame. It is shown that prompt sending of the tumour material, excellent collaboration between clinicians, pathologists within and between centers is essential to ensure timely results and treatment. Development of quicker and cheaper DNA-sequencing methods might greatly facilitate implementation of the molecular-integrated risk profile in routine clinical practice.