PORTEC-4a: Molecular Profile-based Versus Standard Adjuvant Radiotherapy in Endometrial Cancer

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.

Sex

Female

Minimum age

18 Years

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

• DERIVEDvan den Heerik ASVM, Horeweg N, Haverkort MAD, Kuijsters N, Kommoss S, Koppe FLA, Nowee ME, Westerveld H, De Jong MAA, Fruhauf F, Cnossen JS, Mens JWM, Beukema JC, Chargari C, Gillham C, Jurgenliemk-Schulz IM, Vandecasteele K, Hamann M, Kiderlen M, Staebler A, Nijman HW, Wortman BG, Asteinidou E, de Boer SM, van den Hout WB, Verhoeven-Adema KW, Nout RA, Putter H, Bosse T, Creutzberg CL. Molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer (PORTEC-4a): results of a randomised, open-label, phase 3, multicentre, non-inferiority trial. Lancet Oncol. 2026 Jan;27(1):23-35. doi: 10.1016/S1470-2045(25)00612-6. PMID 41449145
• DERIVEDNero C, Ciccarone F, Pietragalla A, Duranti S, Daniele G, Scambia G, Lorusso D. Adjuvant Treatment Recommendations in Early-Stage Endometrial Cancer: What Changes With the Introduction of The Integrated Molecular-Based Risk Assessment. Front Oncol. 2021 Sep 1;11:612450. doi: 10.3389/fonc.2021.612450. eCollection 2021. PMID 34540651
• DERIVEDvan den Heerik ASVM, Horeweg N, Nout RA, Lutgens LCHW, van der Steen-Banasik EM, Westerveld GH, van den Berg HA, Slot A, Koppe FLA, Kommoss S, Mens JWM, Nowee ME, Bijmolt S, Cibula D, Stam TC, Jurgenliemk-Schulz IM, Snyers A, Hamann M, Zwanenburg AG, Coen VLMA, Vandecasteele K, Gillham C, Chargari C, Verhoeven-Adema KW, Putter H, van den Hout WB, Wortman BG, Nijman HW, Bosse T, Creutzberg CL. 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
• DERIVEDWortman BG, Bosse T, Nout RA, Lutgens LCHW, van der Steen-Banasik EM, Westerveld H, van den Berg H, Slot A, De Winter KAJ, Verhoeven-Adema KW, Smit VTHBM, Creutzberg CL; PORTEC Study Group. 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. PMID 30078506