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| ID | Type | Description | Link |
|---|---|---|---|
| UL2011-5336 | Other Grant/Funding Number | Dutch Cancer Society | |
| ISRCTN11659025 | Registry Identifier | ISRCTN Registry | |
| NTR5841 | Registry Identifier | Netherlands Trials Registry |
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| Name | Class |
|---|---|
| Dutch Cancer Society | OTHER |
| Comprehensive Cancer Centre The Netherlands | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Molecular profile based treatment | Experimental | Determination of the integrated clinicopathological and molecular profile to determine adjuvant treatment: observation for favourable profile; vaginal brachytherapy for intermediate profile; external beam radiotherapy for unfavourable profile |
|
| Vaginal brachytherapy | Active Comparator | Adjuvant vaginal brachytherapy (standard treatment) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vaginal brachytherapy | Radiation | Internal radiation of the vaginal vault using a vaginal cylinder, 21 Gy in 3 out-patient sessions over 2 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Vaginal recurrence | Total vaginal recurrence and vaginal recurrence as first failure | 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events | Treatment-related symptoms according to CTCAE v 4.0 | 5 years |
| Health-related cancer-specific quality of life | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Recurrence (vaginal and total) per risk profile | Vaginal, pelvic and distant relapse split by risk profile and compared between the 2 arms | 5 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):
World Health Organization (WHO)-performance status 0-2
Written informed consent
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Carien L. Creutzberg, MD, PhD | Leiden University Medical Center, Dept of Radiation Oncology | Study Chair |
| Remi A. Nout, MD, PhD | ErasmusMC Dept of Radiation Oncology | Principal Investigator |
| Anne-Sophie van den Heerik, MD | Leiden University Medical Center, Dept of Radiation Oncology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University, Vienna | Vienna | Austria | ||||
| University Hospital Gent |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41449145 | Derived | van 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. | |
| 34540651 |
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Specifics will be decided and made public on website at a later stage, most probably from 5 years after final publication onwards
From 5 years after final publication onwards
Upon written application with a clear decription of aim, methods and analysis plan, publication plan, after approval from the study team
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2:1 randomisation to adjuvant treatment assignment based on the integrated molecular risk profile or standard adjuvant vaginal brachytherapy
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Evaluation of outcomes is done without information on randomised arm
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| External beam radiotherapy | Radiation | External beam pelvic radiotherapy on a linear accelerator, 48.6 Gy in 27 out-patients sessions over 5.5 weeks |
|
| Observation | Other | No radiation therapy, but active follow-up and quality of life questionnaires as in the groups who have adjuvant treatment |
|
| 5 years |
| Endometrial cancer-related symptoms and quality of life | Endometrial cancer-related specific symptoms (EORTC EN24 module)- clinically relevant changes on these scales (quite a bit/very much vs no or mild symptoms) | 5 years |
| Relapse-free survival | Relapse-free survival (survival without relapse) | 5 years |
| Survival | Overall survival (all-cause death) | 5 years |
| 5-year vaginal control including treatment for relapse | Long-term local control including salvage treatment for local relapse | 5 years |
| Pelvic recurrence (total) | Total pelvic recurrences | 5 years |
| Pelvic recurrence as first failure | Pelvic recurrence as first failure | 5 years |
| Distant recurrence (total) | Total distant recurrences | 5 years |
| Distant recurrence as first failure | Distant recurrence as first failure | 5 years |
| Endometrial cancer related health care costs | All hospital based health care costs used with primary treatment or during followup for treatment of adverse events and/or treatment for relapse | 5 years |
| Ghent |
| Belgium |
| CEEGOG, General Faculty Hospital and First Faculty of Medicine, Charles University, Prague | Prague | Czechia |
| GINECO group - Institut Goustave Roussy | Paris | France |
| Hôpital Européen Georges-Pompidou | Paris | France |
| Hôpital Tenon | Paris | France |
| Sankt Gertrauden Krankenhaus | Berlin | Germany |
| Kaiserswerther Diakonie | Düsseldorf | Germany |
| Evang. Kliniken Essen-Mitte | Essen | Germany |
| Universitatsklinikum Heidelberg | Heidelberg | Germany |
| Universitätsklinikum Schleswig-Holstein, Campus Lübeck | Lübeck | Germany |
| Rotkreuzklinikum München | Münich | Germany |
| University Hospital | Tübingen | Germany |
| CancerTrials Ireland - St James Hospital (SLRON SJH) | Dublin | Ireland |
| CancerTrials Ireland - St Luke's Hospital (SLRON SLH) | Dublin | Ireland |
| Academic Medical Center | Amsterdam | Netherlands |
| NKI / Antoni van Leeuwenhoekhuis | Amsterdam | Netherlands |
| Radiation Therapy Group | Arnhem | Netherlands |
| Catharina Hospital | Eindhoven | Netherlands |
| Zuidwest Radiotherapy Institute | Flushing | Netherlands |
| University Medical Center Groningen | Groningen | Netherlands |
| Radiotherapy Institute Friesland | Leeuwarden | Netherlands |
| Leiden University Medical Center | Leiden | Netherlands |
| MAASTRO radiation oncology clinic | Maastricht | Netherlands |
| Radboud University Medical Center | Nijmegen | Netherlands |
| ErasmusMC Cancer Center | Rotterdam | Netherlands |
| Haaglanden Medical Center | The Hague | Netherlands |
| Verbeeten institute | Tilburg | Netherlands |
| University Medical Center Utrecht | Utrecht | Netherlands |
| Isala Clinics | Zwolle | Netherlands |
| Kantonsspital Frauenklinik Lucerne | Lucerne | Switzerland |
| Derived |
| Nero 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. |
| 33046573 | Derived | van 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. |
| 30078506 | Derived | Wortman 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. |
| ID | Term |
|---|---|
| D016889 | Endometrial Neoplasms |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
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| ID | Term |
|---|---|
| D019370 | Observation |
| ID | Term |
|---|---|
| D008722 | Methods |
| D008919 | Investigative Techniques |
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