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The brave new world of endometrial cancer

Future implications for adjuvant treatment decisions

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Abstract

Purpose

For many decades, endometrial cancer (EC) has been considered as a homogenous tumor entity with good prognosis. The currently valid risk stratification considers clinical and pathological factors. Treatment recommendations differ considerably from country to country.

Materials and methods

The Cancer Genome Atlas (TCGA) Research Network has shown that ECs should be reclassified into four novel molecular prognostic groups, with the potential of changing adjuvant management of EC patients: ultra-mutated, hyper-mutated, copy-number low, and copy-number high. Clinical examples are shown, and the available literature has been highlighted. The European Society of Gynaecological Oncology (ESGO) guideline for endometrial cancer takes the new classification system into consideration for adjuvant treatment decisions and will be published this year.

Results

In the near future, we expect new treatment recommendations that may differ considerably from the clinicopathologically driven recommendations on the basis of our deeper insight and better understanding of molecular markers in endometrial cancer. The PORTEC 4a study is the only recruiting study which randomizes patients to adjuvant or no adjuvant treatment on the basis of the aforementioned new classification system.

Conclusion

The aim of the new classification is a more personalized adjuvant radio(chemo)therapy decision and better oncologic outcomes or avoidance of overtreatment.

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References

  1. Bokhman JV (1983) Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 15:10–17

    CAS  PubMed  Google Scholar 

  2. Salvesen HB, Haldorsen IS, Trovik J (2012) Markers for individualised therapy in endometrial carcinoma. Lancet Oncol 13:e353–e361

    PubMed  Google Scholar 

  3. ASCO (2020) Uterine Cancer Guide. Cancer.Net. www.cancer.net. Accessed: 29.04.2020

  4. Mullins MA, Beyond Obesity CML (2019) The rising incidence and mortality rates of uterine corpus cancer. J Clin Oncol 37:1851–1853

    PubMed  PubMed Central  Google Scholar 

  5. Clarke MA, Devesa SS, Harvey SV, Wentzensen N (2019) Hysterectomy-corrected uterine corpus cancer incidence trends and differences in relative survival reveal racial disparities and rising rates of Nonendometrioid cancers. J Clin Oncol 37:1895–1908

    PubMed  PubMed Central  Google Scholar 

  6. Robert-Koch-Institut, Zentrum für Krebsregisterdaten (2019) Gebärmutterkörperkrebs. www.krebsdaten.de. Accessed: 29.04.2020

  7. ASTEC/EN.5 Study Group, Blake P, Swart AM, Orton J, Kitchener H, Whelan T, Lukka H et al (2009) Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis. Lancet 373:137–146

    Google Scholar 

  8. de Boer SM, Wortman BG, Bosse T, Powell ME, Singh N, Hollema H, Wilson G, Chowdhury MN, Mileshkin L, Pyman J, Katsaros D, Carinelli S, Fyles A, McLachlin CM, Haie-Meder C, Duvillard P, Nout RA, Verhoeven-Adema KW, Putter H, Creutzberg CL, Smit VTHBM; for PORTEC Study Group (2018) Clinical consequences of upfront pathology review in the randomised PORTEC‑3 trial for high-risk endometrial cancer. Ann Oncol 29(2):424–430. https://doi.org/10.1093/annonc/mdx753

  9. de Boer SM, Wortman BG, Bosse T, Powell ME, Singh N, Hollema H, Wilson G et al (2018) Clinical consequences of upfront pathology review in the randomised PORTEC‑3 trial for high-risk endometrial cancer. Ann Oncol 29:424–430

    PubMed  Google Scholar 

  10. Ballester M, Bendifallah S, Darai E (2017) European guidelines (ESMO-ESGO-ESTRO consensus conference) for the management of endometrial cancer. Bull Cancer 104:1032–1038

    PubMed  Google Scholar 

  11. (2018) Interdisziplinäre Leitlinie zur Diagnostik TuNdPmE. Registrierungsnummer: 032-034OL, Entwicklungsstufe: S3. www.awmf.org. Accessed: 29.04.2020

  12. Cancer Genome Atlas Research Network, Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H et al (2013) Integrated genomic characterization of endometrial carcinoma. Nature 497:67–73

    Google Scholar 

  13. Raffone A, Travaglino A, Mascolo M, Carbone L, Guida M, Insabato L, Zullo F (2019) TCGA molecular groups of endometrial cancer: Pooled data about prognosis. Gynecol Oncol 155:374–383

    CAS  PubMed  Google Scholar 

  14. Karnezis AN, Leung S, Magrill J, McConechy MK, Yang W, Chow C, Kobel M et al (2017) Evaluation of endometrial carcinoma prognostic immunohistochemistry markers in the context of molecular classification. J Pathol Clin Res 3:279–293

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Britton H, Huang L, Lum A, Leung S, Shum K, Kale M, Burleigh A et al (2019) Molecular classification defines outcomes and opportunities in young women with endometrial carcinoma. Gynecol Oncol 153:487–495

    PubMed  Google Scholar 

  16. Creutzberg CL, Nout RA, Lybeert ML, Warlam-Rodenhuis CC, Jobsen JJ, Mens JW, Lutgens LC et al (2011) Fifteen-year radiotherapy outcomes of the randomized PORTEC‑1 trial for endometrial carcinoma. Int J Radiat Oncol Biol Phys 81:e631–e638

    PubMed  Google Scholar 

  17. de Boer SM, Nout RA, Jurgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, Mens JW et al (2015) Long-term impact of endometrial cancer diagnosis and treatment on health-related quality of life and cancer survivorship: results from the randomized PORTEC‑2 trial. Int J Radiat Oncol Biol Phys 93:797–809

    PubMed  Google Scholar 

  18. Wortman BG, Creutzberg CL, Putter H, Jurgenliemk-Schulz IM, Jobsen JJ, Lutgens LCHW, van der Steen-Banasik EM et al (2018) Ten-year results of the PORTEC‑2 trial for high-intermediate risk endometrial carcinoma: improving patient selection for adjuvant therapy. Br J Cancer 119:1067–1074

    CAS  PubMed  PubMed Central  Google Scholar 

  19. de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, Colombo A, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Carinelli S, Provencher D, Hanzen C, Lutgens LCHW, Smit VTHBM, Singh N, Do V, D’Amico R, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC study group (2018) Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol 19(3):295–309. https://doi.org/10.1016/S1470-2045(18)30079-2

  20. Creutzberg CL (2004) GOG-99: ending the controversy regarding pelvic radiotherapy for endometrial carcinoma? Gynecol Oncol 92:740–743

    PubMed  Google Scholar 

  21. Stelloo E, Nout RA, Osse EM, Jurgenliemk-Schulz IJ, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM et al (2016) Improved risk assessment by integrating molecular and Clinicopathological factors in early-stage Endometrial cancer-combined analysis of the PORTEC cohorts. Clin Cancer Res 22:4215–4224

    CAS  PubMed  Google Scholar 

  22. Stelloo E, Bosse T, Nout RA, MacKay HJ, Church DN, Nijman HW, Leary A et al (2015) Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative. Mod Pathol 28:836–844

    CAS  PubMed  Google Scholar 

  23. Reijnen C, Kusters-Vandevelde HVN, Prinsen CF, Massuger LFAG, Snijders MPML, Kommoss S, Brucker SY et al (2019) Mismatch repair deficiency as a predictive marker for response to adjuvant radiotherapy in endometrial cancer. Gynecol Oncol 154:124–130

    CAS  PubMed  Google Scholar 

  24. Van Gool IC, Rayner E, Osse EM, Nout RA, Creutzberg CL, Tomlinson IPM, Church DN et al (2018) Adjuvant treatment for POLE proofreading domain-mutant cancers: sensitivity to radiotherapy, chemotherapy, and Nucleoside analogues. Clin Cancer Res 24:3197–3203

    PubMed  Google Scholar 

  25. Wortman BG, Bosse T, Nout RA, Lutgens L, van der Steen-Banasik EM, Westerveld H, van den Berg H et al (2018) Molecular-integrated risk profile to determine adjuvant radiotherapy in endometrial cancer: Evaluation of the pilot phase of the PORTEC-4a trial. Gynecol Oncol 151:69–75

    CAS  PubMed  Google Scholar 

  26. Matei D, Filiaci V, Randall ME, Mutch D, Steinhoff MM, DiSilvestro PA, Moxley KM et al (2019) Adjuvant chemotherapy plus radiation for locally advanced Endometrial cancer. N Engl J Med 380:2317–2326

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Randall ME, Filiaci V, McMeekin DS, von Gruenigen V, Huang H, Yashar CM, Mannel RS et al (2019) Phase III Trial: Adjuvant Pelvic Radiation Therapy Versus Vaginal Brachytherapy Plus Paclitaxel/Carboplatin in High-Intermediate and High-Risk Early Stage Endometrial Cancer. J Clin Oncol 37:1810–1818

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Wortman BG, Nout RA, Bosse T, Creutzberg CL (2019) Selecting Adjuvant treatment for Endometrial carcinoma using molecular risk factors. Curr Oncol Rep 21:83

    PubMed  PubMed Central  Google Scholar 

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Correspondence to S. Marnitz.

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Conflict of interest

S. Marnitz, T. Waltar, C. Köhler, A. Mustea, and B. Schömig-Markiefka declare that they have no competing interests.

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Marnitz, S., Waltar, T., Köhler, C. et al. The brave new world of endometrial cancer. Strahlenther Onkol 196, 963–972 (2020). https://doi.org/10.1007/s00066-020-01632-w

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  • DOI: https://doi.org/10.1007/s00066-020-01632-w

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