What Is the Role of Adjuvant Radiotherapy and Chemotherapy in Endometrial Cancer?

  • Thomas Hogberg
  • Carien L. Creutzberg


In this chapter, the evidence on the role of adjuvant radiotherapy and/or chemotherapy in the treatment of patients with endometrial cancer is discussed, with emphasis on the controversial issues and pro/con discussions. Ongoing issues of debate for which future trials should provide evidence are highlighted. Risk-based treatment selection is emphasized, with the aim of sparing many patients with low-risk endometrial cancer unnecessary toxicities of adjuvant treatment. Ongoing and future research is mainly directed at investigating the role of adjuvant chemotherapy in patients with high-risk disease to improve outcomes.


Endometrial Cancer Endometrial Carcinoma Myometrial Invasion Gynecology Oncology Group Vaginal Brachytherapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    WHO Cancer Mondial. GLOBOCAN.
  2. 2.
    Altekruse SF, Kosary CL, Krapcho M, Neyman N, Aminou R, Waldron W, Ruhl J, Howlader N, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Cronin K, Chen HS, Feuer EJ, Stinchcomb DG, Edwards BKe. SEER Cancer Statistics Review, 1975–2007. Bethesda: National Cancer Institute; 2010. Based on Nov 2009 SEER data submission, posted to the SEER web site, 2010.
  3. 3.
  4. 4.
    Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, Benedet JL, Heintz AP, Ngan HY, Pecorelli S. Carcinoma of the corpus uteri. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet. 2006;95 Suppl 1:S105–43.PubMedCrossRefGoogle Scholar
  5. 5.
    Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983;15:10–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Bansal N, Yendluri V, Wenham RM. The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies. Cancer Control. 2009;16:8–13.PubMedGoogle Scholar
  7. 7.
    Engelsen IB, Akslen LA, Salvesen HB. Biologic markers in endometrial cancer treatment. APMIS. 2009;117:693–707.PubMedCrossRefGoogle Scholar
  8. 8.
    Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group study. Cancer. 1987;60:2035–41.PubMedCrossRefGoogle Scholar
  9. 9.
    Mariani A, Dowdy SC, Cliby WA, Gostout BS, Jones MB, Wilson TO, Podratz KC. Prospective assessment of lymphatic dissemination in endometrial cancer: a paradigm shift in surgical staging. Gynecol Oncol. 2008;109:11–8.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet. 2009;105:103–4.PubMedCrossRefGoogle Scholar
  11. 11.
    Aalders J, Abeler V, Kolstad P, Onsrud M. Postoperative external irradiation and prognostic parameters in stage I endometrial carcinoma: clinical and histopathologic study of 540 patients. Obstet Gynecol. 1980;56:419–27.PubMedGoogle Scholar
  12. 12.
    Creutzberg CL, van Putten WL, Koper PC, Lybeert ML, Jobsen JJ, Warlam-Rodenhuis CC, De Winter KA, Lutgens LC, van den Bergh AC, van de Steen-Banasik E, Beerman H, van Lent M. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet. 2000;355:1404–11.PubMedCrossRefGoogle Scholar
  13. 13.
    Keys HM, Roberts JA, Brunetto VL, Zaino RJ, Spirtos NM, Bloss JD, Pearlman A, Maiman MA, Bell JG. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004;92:744–51.PubMedCrossRefGoogle Scholar
  14. 14.
    Blake P, Swart AM, Orton J, Kitchener H, Whelan T, Lukka H, Eisenhauer E, Bacon M, Tu D, Parmar MK, Amos C, Murray C, Qian W. 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. 2009;373:137–46.PubMedCrossRefGoogle Scholar
  15. 15.
    Nout RA, Smit VTHB, Putter H, Jurgenliemk-Schulz IM, Jobsen JJ, Lutgens LCHW, van der Steen-Banasik EM, Mens JWM, Slot A, Stenfert Kroese MC, van Bunningen BNFM, Ansink AC, van Putten WLJ, Creutzberg CL. Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial carcinoma of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet. 2010;375:816–23.PubMedCrossRefGoogle Scholar
  16. 16.
    Scholten AN, van Putten WL, Beerman H, Smit VT, Koper PC, Lybeert ML, Jobsen JJ, Warlam-Rodenhuis CC, De Winter KA, Lutgens LC, van Lent M, Creutzberg CL. Postoperative radiotherapy for Stage 1 endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review. Int J Radiat Oncol Biol Phys. 2005;63:834–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Creutzberg CL. Survival after relapse in patients with endometrial cancer: results from a randomized trial - Response to the letter to the editor by Pijnenborg et al. Gynecol Oncol. 2004;92:384–6.CrossRefGoogle Scholar
  18. 18.
    Nout RA, Putter H, Jurgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, Mens JW, Slot A, Stenfert Kroese MC, van Bunningen BN, Smit VT, Nijman HW, van den Tol PP, Creutzberg CL. Quality of life after pelvic radiotherapy or vaginal brachytherapy for endometrial cancer: first results of the randomized PORTEC-2 trial. J Clin Oncol. 2009;27:3547–56.PubMedCrossRefGoogle Scholar
  19. 19.
    Nout RA, Putter H, Jurgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, Mens JW, Slot A, Stenfert Kroese MC, Nijman HW, van de Poll-Franse LV, Creutzberg CL. Five-year quality of life of endometrial cancer patients treated in the randomised Post Operative Radiation Therapy in Endometrial Cancer (PORTEC-2) trial and comparison with norm data. Eur J Cancer. 2012;48:1638–48.PubMedCrossRefGoogle Scholar
  20. 20.
    Kong A, Simera I, Collingwood M, Williams C, Kitchener H. Adjuvant radiotherapy for stage I endometrial cancer: systematic review and meta-analysis. Ann Oncol. 2007;18:1595–604.PubMedCrossRefGoogle Scholar
  21. 21.
    Thomas GM. A role for adjuvant radiation in clinically early carcinoma of the endometrium? Int J Gynecol Cancer. 2010;20:S64–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Mariani A, Dowdy SC, Cliby WA, Haddock MG, Keeney GL, Lesnick TG, Podratz KC. Efficacy of systematic lymphadenectomy and adjuvant radiotherapy in node-positive endometrial cancer patients. Gynecol Oncol. 2006;101:200–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Cragun JM, Havrilesky LJ, Calingaert B, Synan I, Secord AA, Soper JT, Clarke-Pearson DL, Berchuck A. Retrospective analysis of selective lymphadenectomy in apparent early-stage endometrial cancer. J Clin Oncol. 2005;23:3668–75.PubMedCrossRefGoogle Scholar
  24. 24.
    Chan JK, Cheung MK, Huh WK, Osann K, Husain A, Teng NN, Kapp DS. Therapeutic role of lymph node resection in endometrioid corpus cancer: a study of 12,333 patients. Cancer. 2006;107:1823–30.PubMedCrossRefGoogle Scholar
  25. 25.
    Smith DC, Macdonald OK, Lee CM, Gaffney DK. Survival impact of lymph node dissection in endometrial adenocarcinoma: a surveillance, epidemiology, and end results analysis. Int J Gynecol Cancer. 2008;18:255–61.PubMedCrossRefGoogle Scholar
  26. 26.
    Todo Y, Kato H, Kaneuchi M, Watari H, Takeda M, Sakuragi N. Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis. Lancet. 2010;375:1165–72.PubMedCrossRefGoogle Scholar
  27. 27.
    Kitchener H, Swart AM, Qian Q, Amos C, Parmar MK. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study. Lancet. 2009;373:125–36.PubMedCrossRefGoogle Scholar
  28. 28.
    Benedetti PP, Basile S, Maneschi F, Alberto LA, Signorelli M, Scambia G, Angioli R, Tateo S, Mangili G, Katsaros D, Garozzo G, Campagnutta E, Donadello N, Greggi S, Melpignano M, Raspagliesi F, Ragni N, Cormio G, Grassi R, Franchi M, Giannarelli D, Fossati R, Torri V, Amoroso M, Croce C, Mangioni C. Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. J Natl Cancer Inst. 2008;100:1707–16.CrossRefGoogle Scholar
  29. 29.
    May K, Bryant A, Dickinson HO, Kehoe S, Morrison J. Lymphadenectomy for the management of endometrial cancer. Cochrane Database Syst Rev. 2010;CD007585.Google Scholar
  30. 30.
    Susumu N, Sagae S, Udagawa Y, Niwa K, Kuramoto H, Satoh S, Kudo R. Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study. Gynecol Oncol. 2008;108:226–33.PubMedCrossRefGoogle Scholar
  31. 31.
    Maggi R, Lissoni A, Spina F, Melpignano M, Zola P, Favalli G, Colombo A, Fossati R. Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial. Br J Cancer. 2006;95:266–71.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Klopp AH, Jhingran A, Ramondetta L, Lu K, Gershenson DM, Eifel PJ. Node-positive adenocarcinoma of the endometrium: outcome and patterns of recurrence with and without external beam irradiation. Gynecol Oncol. 2009;115:6–11.PubMedCrossRefGoogle Scholar
  33. 33.
    Mundt AJ, McBride R, Rotmensch J, Waggoner SE, Yamada SD, Connell PP. Significant pelvic recurrence in high-risk pathologic stage I–IV endometrial carcinoma patients after adjuvant chemotherapy alone: implications for adjuvant radiation therapy. Int J Radiat Oncol Biol Phys. 2001;50:1145–53.PubMedCrossRefGoogle Scholar
  34. 34.
    Humber CE, Tierney JF, Symonds RP, Collingwood M, Kirwan J, Williams C, Green JA. Chemotherapy for advanced, recurrent or metastatic endometrial cancer: a systematic review of Cochrane collaboration. Ann Oncol. 2007;18:409–20.PubMedCrossRefGoogle Scholar
  35. 35.
    Temkin SM, Fleming G. Current treatment of metastatic endometrial cancer. Cancer Control. 2009;16:38–45.PubMedGoogle Scholar
  36. 36.
    Aapro MS, Van Wijk FH, Bolis G, Chevallier B, Van Der Burg ME, Poveda A, De Oliveira CF, Tumolo S, di Scotto Palumbo V, Piccart M, Franchi M, Zanaboni F, Lacave AJ, Fontanelli R, Favalli G, Zola P, Guastalla JP, Rosso R, Marth C, Nooij M, Presti M, Scarabelli C, Splinter TA, Ploch E, Beex LV, Ten Bokkel HW, Forni M, Melpignano M, Blake P, Kerbrat P, Mendiola C, Cervantes A, Goupil A, Harper PG, Madronal C, Namer M, Scarfone G, Stoot JE, Teodorovic I, Coens C, Vergote I, Vermorken JB. Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group. Ann Oncol. 2003;14:441–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Thigpen JT, Brady MF, Homesley HD, Malfetano J, DuBeshter B, Burger RA, Liao S. Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: Gynecologic Oncology Group study. J Clin Oncol. 2004;22:3902–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Fleming GF, Brunetto VL, Cella D, Look KY, Reid GC, Munkarah AR, Kline R, Burger RA, Goodman A, Burks RT. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2004;22:2159–66.PubMedCrossRefGoogle Scholar
  39. 39.
    Hoskins PJ, Swenerton KD, Pike JA, Wong F, Lim P, Acquino-Parsons C, Lee N. Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study. J Clin Oncol. 2001;19:4048–53.PubMedGoogle Scholar
  40. 40.
    Sorbe B, Andersson H, Boman K, Rosenberg P, Kalling M. Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel-long-term follow-up. Int J Gynecol Cancer. 2008;18:803–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Akram T, Maseelall P, Fanning J. Carboplatin and paclitaxel for the treatment of advanced or recurrent endometrial cancer. Am J Obstet Gynecol. 2005;192:1365–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Michener CM, Peterson G, Kulp B, Webster KD, Markman M. Carboplatin plus paclitaxel in the treatment of advanced or recurrent endometrial carcinoma. J Cancer Res Clin Oncol. 2005;131:581–4.PubMedCrossRefGoogle Scholar
  43. 43.
    Scudder SA, Liu PY, Wilczynski SP, Smith HO, Jiang C, Hallum III AV 3rd, Smith GB, Hannigan EV, Markman M, Alberts DS. Paclitaxel and carboplatin with amifostine in advanced, recurrent, or refractory endometrial adenocarcinoma: a phase II study of the Southwest Oncology Group. Gynecol Oncol. 2005;96:610–5.PubMedCrossRefGoogle Scholar
  44. 44.
    Arimoto T, Nakagawa S, Yasugi T, Yoshikawa H, Kawana K, Yano T, Taketani Y. Treatment with paclitaxel plus carboplatin, alone or with irradiation, of advanced or recurrent endometrial carcinoma. Gynecol Oncol. 2007;104:32–5.PubMedCrossRefGoogle Scholar
  45. 45.
    Sovak MA, Dupont J, Hensley ML, Ishill N, Gerst S, Abu-Rustum N, Anderson S, Barakat R, Konner J, Poyner E, Sabbatini P, Spriggs DR, Aghajanian C. Paclitaxel and carboplatin in the treatment of advanced or recurrent endometrial cancer: a large retrospective study. Int J Gynecol Cancer. 2007;17:197–203.PubMedCrossRefGoogle Scholar
  46. 46.
    Homesley HD, Blessing JA, Sorosky J, Reid G, Look KY. Phase II trial of liposomal doxorubicin at 40 mg/m(2) every 4 weeks in endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2005;98:294–8.PubMedCrossRefGoogle Scholar
  47. 47.
    du Bois A, Pfisterer J, Burchardi N, Loibl S, Huober J, Wimberger P, Burges A, Stahle A, Jackisch C, Kolbl H. Combination therapy with pegylated liposomal doxorubicin and carboplatin in gynecologic malignancies: a prospective phase II study of the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and Kommission Uterus (AGO-K-Ut). Gynecol Oncol. 2007;107:518–25.PubMedCrossRefGoogle Scholar
  48. 48.
    Pignata S, Scambia G, Pisano C, Breda E, Di Maio M, Greggi S, Ferrandina G, Lorusso D, Zagonel V, Febbraro A, Riva N, De Rosa V, Gallo C, Perrone F. A multicentre phase II study of carboplatin plus pegylated liposomal doxorubicin as first-line chemotherapy for patients with advanced or recurrent endometrial carcinoma: the END-1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) group. Br J Cancer. 2007;96:1639–43.Google Scholar
  49. 49.
    Vandenput I, Vergote I, Leunen K, Berteloot P, Neven P, Amant F. Leuven dose-dense paclitaxel/carboplatin regimen in patients with primary advanced or recurrent endometrial carcinoma. Int J Gynecol Cancer. 2009;19:1147–51.PubMedCrossRefGoogle Scholar
  50. 50.
    Nomura H, Aoki D, Takahashi F, Katsumata N, Watanabe Y, Konishi I, Jobo T, Hatae M, Hiura M, Yaegashi N. Randomized phase II study comparing docetaxel plus cisplatin, docetaxel plus carboplatin, and paclitaxel plus carboplatin in patients with advanced or recurrent endometrial carcinoma: a Japanese Gynecologic Oncology Group study (JGOG2041). Ann Oncol. 2011;22:636–42.PubMedCrossRefGoogle Scholar
  51. 51.
    Aoki D. Completion of patient enrollment to JGOG2043, a randomized phase III trial for endometrial cancer. JGOG International. 2012 September No.7.
  52. 52.
    Miller D, Felicias V, Fleming G, Mannel R, Cohn D, Matsumoto T, Tewari K, DiSilvestro P, Pearl M, Zaino R. Late-Breaking Abstract 1: Randomized phase III noninferiority trial of first line chemotherapy for metastatic or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. Gynecologic Oncology 2012;125:771.Google Scholar
  53. 53.
    Randall ME, Filiaci VL, Muss H, Spirtos NM, Mannel RS, Fowler J, Thigpen JT, Benda JA. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2006;24:36–44.PubMedCrossRefGoogle Scholar
  54. 54.
    Hogberg T, Signorelli M, De Oliveira CF, Fossati R, Lissoni AA, Sorbe B, Andersson H, Grenman S, Lundgren C, Rosenberg P, Boman K, Tholander B, Scambia G, Reed N, Cormio G, Tognon G, Clarke J, Sawicki T, Zola P, Kristensen G. Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer–results from two randomised studies. Eur J Cancer. 2010;46:2422–31.PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Morrow CP, Bundy BN, Homesley HD, Creasman WT, Hornback NB, Kurman R, Thigpen JT. Doxorubicin as an adjuvant following surgery and radiation therapy in patients with high-risk endometrial carcinoma, stage I and occult stage II: a Gynecologic Oncology Group study. Gynecol Oncol. 1990;36:166–71.PubMedCrossRefGoogle Scholar
  56. 56.
    Kuoppala T, Maenpaa J, Tomas E, Puistola U, Salmi T, Grenman S, Lehtovirta P, Fors M, Luukkaala T, Sipila P. Surgically staged high-risk endometrial cancer: randomized study of adjuvant radiotherapy alone vs. sequential chemo-radiotherapy. Gynecol Oncol. 2008;110:190–5.PubMedCrossRefGoogle Scholar
  57. 57.
    McMeekin DS, Filiaci VL, Thigpen JT, Gallion HH, Fleming GF, Rodgers WH. The relationship between histology and outcome in advanced and recurrent endometrial cancer patients participating in first-line chemotherapy trials: a Gynecologic Oncology Group study. Gynecol Oncol. 2007;106:16–22.PubMedCrossRefGoogle Scholar
  58. 58.
    Greven K, Winter K, Underhill K, Fontenesci J, Cooper J, Burke T. Final analysis of RTOG 9708: adjuvant postoperative irradiation combined with cisplatin/paclitaxel chemotherapy following surgery for patients with high-risk endometrial cancer. Gynecol Oncol. 2006;103:155–9.PubMedCrossRefGoogle Scholar
  59. 59.
  60. 60.
  61. 61.
  62. 62.
  63. 63.
  64. 64.
    Creutzberg CL. Adjuvant chemotherapy for endometrial cancer: unproven. Int J Gynecol Cancer. 2010;20:1105–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Dedes KJ, Wetterskog D, Ashworth A, Kaye SB, Reis-Filho JS. Emerging therapeutic targets in endometrial cancer. Nat Rev Clin Oncol. 2011;8:261–71.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  1. 1.Department of Cancer EpidemiologyLund University HospitalLundSweden
  2. 2.Radiation OncologyLeiden University Medical CenterLeidenThe Netherlands

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