Clinical Behavior and Treatment of Endometrial Cancer

  • Divya Gupta
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 943)


Endometrial cancer is the most common gynecologic malignancy diagnosed in women in the developed nations. It affects a disproportionate number of reproductive-aged women. While the overall prognosis is good compared to other cancers affecting women, the pathogenesis and clinical behavior of endometrial cancer are heterogeneous. The risk factors associated with the type I and type II endometrial cancers and their pathogenesis will be discussed, as well as the evaluation and primary treatment of women with endometrial cancer. The chapter will also focus on risk stratification for recurrence after surgery and role of adjuvant treatments. Finally, the treatment of recurrent endometrial cancer will be presented.


Endometrial cancer Risk factors Lynch syndrome Fertility sparing Chemotherapy Radiation Surgery Minimally invasive surgery Lymphadenectomy 


  1. 1.
    Eheman C, Henley SJ, Ballard-Barbash R, Jacobs EJ, Schymura MJ, Noone AM, et al. Annual report to the nation on the status of cancer, 1975–2008, featuring cancers associated with excess weight and lack of sufficient physical activity. Cancer. 2012;118(9):2338–66.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013 [cited Available from: Accessed 18 Feb 2015].
  3. 3.
    Smith RA, von Eschenbach AC, Wender R, Levin B, Byers T, Rothenberger D, et al. American Cancer Society guidelines for the early detection of cancer: update of early detection guidelines for prostate, colorectal, and endometrial cancers. Also: update 2001--testing for early lung cancer detection. CA Cancer J Clin. 2001;51(1):38–75. quiz 7-80.CrossRefPubMedGoogle Scholar
  4. 4.
    Aarnio M, Mecklin JP, Aaltonen LA, Nystrom-Lahti M, Jarvinen HJ. Life-time risk of different cancers in hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Int J Cancer. 1995;64(6):430–3.CrossRefPubMedGoogle Scholar
  5. 5.
    Obermair A, Youlden DR, Young JP, Lindor NM, Baron JA, Newcomb P, et al. Risk of endometrial cancer for women diagnosed with HNPCC-related colorectal carcinoma. Int J Cancer. 2010;127(11):2678–84.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Pilarski R, Burt R, Kohlman W, Pho L, Shannon KM, Swisher E. Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria. J Natl Cancer Inst. 2013;105(21):1607–16.CrossRefPubMedGoogle Scholar
  7. 7.
    Lavie O, Hornreich G, Ben-Arie A, Rennert G, Cohen Y, Keidar R, et al. BRCA germline mutations in Jewish women with uterine serous papillary carcinoma. Gynecol Oncol. 2004;92(2):521–4.CrossRefPubMedGoogle Scholar
  8. 8.
    Biron-Shental T, Drucker L, Altaras M, Bernheim J, Fishman A. High incidence of BRCA1-2 germline mutations, previous breast cancer and familial cancer history in Jewish patients with uterine serous papillary carcinoma. Eur J Surg Oncol. 2006;32(10):1097–100.CrossRefPubMedGoogle Scholar
  9. 9.
    Jamison PM, Altekruse SF, Chang JT, Zahn J, Lee R, Noone AM, et al. Site-specific factors for cancer of the corpus uteri from SEER registries: collaborative stage data collection system, version 1 and version 2. Cancer. 2014;120 Suppl 23:3836–45.CrossRefPubMedGoogle Scholar
  10. 10.
    Dijkhuizen FP, Mol BW, Brolmann HA, Heintz AP. The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis. Cancer. 2000;89(8):1765–72.CrossRefPubMedGoogle Scholar
  11. 11.
    ACOG Committee Opinion No. 426: The role of transvaginal ultrasonography in the evaluation of postmenopausal bleeding. Obstet Gynecol. 2009;113(2 Pt 1):462–4.Google Scholar
  12. 12.
    Polyzos NP, Mauri D, Tsioras S, Messini CI, Valachis A, Messinis IE. Intraperitoneal dissemination of endometrial cancer cells after hysteroscopy: a systematic review and meta-analysis. Int J Gynecol Cancer. 2010;20(2):261–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Practice bulletin no. 136: management of abnormal uterine bleeding associated with ovulatory dysfunction. Obstet Gynecol. 2013;122(1):176–85.Google Scholar
  14. 14.
    Schnatz PF, Guile M, O’Sullivan DM, Sorosky JI. Clinical significance of atypical glandular cells on cervical cytology. Obstet Gynecol. 2006;107(3):701–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Lu KH, Daniels M. Endometrial and ovarian cancer in women with Lynch syndrome: update in screening and prevention. Fam Cancer. 2013;12(2):273–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW. ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015;110(2):223–62. quiz 63.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Lee SC, Kaunitz AM, Sanchez-Ramos L, Rhatigan RM. The oncogenic potential of endometrial polyps: a systematic review and meta-analysis. Obstet Gynecol. 2010;116(5):1197–205.CrossRefPubMedGoogle Scholar
  18. 18.
    Kinkel K, Kaji Y, Yu KK, Segal MR, Lu Y, Powell CB, et al. Radiologic staging in patients with endometrial cancer: a meta-analysis. Radiology. 1999;212(3):711–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Selman TJ, Mann CH, Zamora J, Khan KS. A systematic review of tests for lymph node status in primary endometrial cancer. BMC Womens Health. 2008;8:8.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Park JY, Kim EN, Kim DY, Suh DS, Kim JH, Kim YM, et al. Comparison of the validity of magnetic resonance imaging and positron emission tomography/computed tomography in the preoperative evaluation of patients with uterine corpus cancer. Gynecol Oncol. 2008;108(3):486–92.CrossRefPubMedGoogle Scholar
  21. 21.
    Creasman W. Revised FIGO staging for carcinoma of the endometrium. Int J Gynaecol Obstet. 2009;105(2):109.CrossRefPubMedGoogle Scholar
  22. 22.
    Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983;15(1):10–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67–73.CrossRefPubMedGoogle Scholar
  24. 24.
    Hendrickson M, Ross J, Eifel P, Martinez A, Kempson R. Uterine papillary serous carcinoma: a highly malignant form of endometrial adenocarcinoma. Am J Surg Pathol. 1982;6(2):93–108.CrossRefPubMedGoogle Scholar
  25. 25.
    Hamilton CA, Cheung MK, Osann K, Chen L, Teng NN, Longacre TA, et al. Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers. Br J Cancer. 2006;94(5):642–6.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Wheeler DT, Bell KA, Kurman RJ, Sherman ME. Minimal uterine serous carcinoma: diagnosis and clinicopathologic correlation. Am J Surg Pathol. 2000;24(6):797–806.CrossRefPubMedGoogle Scholar
  27. 27.
    Hui P, Kelly M, O’Malley DM, Tavassoli F, Schwartz PE. Minimal uterine serous carcinoma: a clinicopathological study of 40 cases. Mod Pathol. 2005;18(1):75–82.CrossRefPubMedGoogle Scholar
  28. 28.
    Abeler VMKK. Clear cell carcinoma of the endometrium: a histopathological and clinical studies of 97 patients. Gynecol Oncol. 1991;40:207–17.CrossRefPubMedGoogle Scholar
  29. 29.
    Wolfson AH, Brady MF, Rocereto T, Mannel RS, Lee YC, Futoran RJ, et al. A gynecologic oncology group randomized phase III trial of whole abdominal irradiation (WAI) vs. cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I-IV carcinosarcoma (CS) of the uterus. Gynecol Oncol. 2007;107(2):177–85.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Zelmanowicz A, Hildesheim A, Sherman ME, Sturgeon SR, Kurman RJ, Barrett RJ, et al. Evidence for a common etiology for endometrial carcinomas and malignant mixed mullerian tumors. Gynecol Oncol. 1998;69(3):253–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Tornos C, Silva EG, Khorana SM, Burke TW. High-stage endometrioid carcinoma of the ovary. Prognostic significance of pure versus mixed histologic types. Am J Surg Pathol. 1994;18(7):687–93.CrossRefPubMedGoogle Scholar
  32. 32.
    Trimble CL, Kauderer J, Zaino R, Silverberg S, Lim PC, Burke II JJ, et al. Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Cancer. 2006;106(4):812–9.CrossRefPubMedGoogle Scholar
  33. 33.
    Boronow RC, Morrow CP, Creasman WT, Disaia PJ, Silverberg SG, Miller A, et al. Surgical staging in endometrial cancer: clinical-pathologic findings of a prospective study. Obstet Gynecol. 1984;63(6):825–32.PubMedGoogle Scholar
  34. 34.
    Creaseman 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.CrossRefGoogle Scholar
  35. 35.
    Mariani A, Webb MJ, Keeney GL, Haddock MG, Calori G, Podratz KC. Low-risk corpus cancer: is lymphadenectomy or radiotherapy necessary? Am J Obstet Gynecol. 2000;182(6):1506–19.CrossRefPubMedGoogle Scholar
  36. 36.
    Wethington SL, Barrena Medel NI, Wright JD, Herzog TJ. Prognostic significance and treatment implications of positive peritoneal cytology in endometrial adenocarcinoma: unraveling a mystery. Gynecol Oncol. 2009;115(1):18–25.CrossRefPubMedGoogle Scholar
  37. 37.
    Garg G, Gao F, Wright JD, Hagemann AR, Mutch DG, Powell MA. Positive peritoneal cytology is an independent risk-factor in early stage endometrial cancer. Gynecol Oncol. 2013;128(1):77–82.CrossRefPubMedGoogle Scholar
  38. 38.
    Walker JL, Piedmonte MR, Spirtos NM, Eisenkop SM, Schlaerth JB, Mannel RS, et al. Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group Study LAP2. J Clin Oncol. 2009;27(32):5331–6.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Walker JL, Piedmonte MR, Spirtos NM, Eisenkop SM, Schlaerth JB, Mannel RS, et al. Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group LAP2 Study. J Clin Oncol. 2012;30(7):695–700.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Keys HM, Roberts JA, Brunetto VL, Zaino RJ, Spirtos NM, Bloss JD, et al. 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(3):744–51.CrossRefPubMedGoogle Scholar
  41. 41.
    The writing committee on behalf of the ASTEC study group. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study. Lancet. 2009;373:125–36.CrossRefPubMedCentralGoogle Scholar
  42. 42.
    Mariani A, Dowdy SC, Cliby WA, Gostout BS, Jones MB, Wilson TO, et al. Prospective assessment of lymphatic dissemination in endometrial cancer: a paradigm shift in surgical staging. Gynecol Oncol. 2008;109(1):11–8.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Boruta 2nd DM, Gehrig PA, Fader AN, Olawaiye AB. Management of women with uterine papillary serous cancer: a Society of Gynecologic Oncology (SGO) review. Gynecol Oncol. 2009;115(1):142–53.CrossRefPubMedGoogle Scholar
  44. 44.
    Moller KA, Gehrig PA, Van Le L, Secord AA, Schorge J. The role of optimal debulking in advanced stage serous carcinoma of the uterus. Gynecol Oncol. 2004;94(1):170–4.CrossRefPubMedGoogle Scholar
  45. 45.
    Creutzberg CL, van Putten WLJ, Koper PCM, Lybeert MLM, Jobsen JJ, Wárlám-Rodenhuis CC, et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. Lancet. 2000;355(9213):1404–11.CrossRefPubMedGoogle Scholar
  46. 46.
    Nout RA, Smit VT, Putter H, Jürgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, Mens JW, Slot A, Kroese MC, van Bunningen BN, Ansink AC, van Putten WL, Creutzberg CL, for the PORTEC Study Group. Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet. 2010;375:816–23.Google Scholar
  47. 47.
    Kong A, Johnson N, Kitchener HC, Lawrie TA. Adjuvant radiotherapy for stage I endometrial cancer. Cochrane Database Syst Rev. 2012;3:CD003916.Google Scholar
  48. 48.
    The writing committee on behalf of the ASTEC study group. 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.Google Scholar
  49. 49.
    Creutzberg CL, van Putten WL, Warlam-Rodenhuis CC, van den Bergh AC, de Winter KA, Koper PC, et al. Outcome of high-risk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the Postoperative Radiation Therapy in Endometrial Carcinoma Trial. J Clin Oncol. 2004;22(7):1234–41.CrossRefPubMedGoogle Scholar
  50. 50.
    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(1):155–9.CrossRefPubMedGoogle Scholar
  51. 51.
    Susumu N, Sagae S, Udagawa Y, Niwa K, Kuramoto H, Satoh S, et al. 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(1):226–33.CrossRefPubMedGoogle Scholar
  52. 52.
    Landrum LM, Nugent EK, Zuna RE, Syzek E, Mannel RS, Moore KN, et al. Phase II trial of vaginal cuff brachytherapy followed by chemotherapy in early stage endometrial cancer patients with high-intermediate risk factors. Gynecol Oncol. 2014;132(1):50–4.CrossRefPubMedGoogle Scholar
  53. 53.
    Galaal K, Al Moundhri M, Bryant A, Lopes AD, Lawrie TA. Adjuvant chemotherapy for advanced endometrial cancer. Cochrane Database Syst Rev. 2014;5:CD010681.Google Scholar
  54. 54.
    Secord AA, Geller MA, Broadwater G, Holloway R, Shuler K, Dao NY, et al. A multicenter evaluation of adjuvant therapy in women with optimally resected stage IIIC endometrial cancer. Gynecol Oncol. 2013;128(1):65–70.CrossRefPubMedGoogle Scholar
  55. 55.
    Einstein MH, Frimer M, Kuo DY, Reimers LL, Mehta K, Mutyala S, et al. Phase II trial of adjuvant pelvic radiation “sandwiched” between combination paclitaxel and carboplatin in women with uterine papillary serous carcinoma. Gynecol Oncol. 2012;124(1):21–5.CrossRefPubMedGoogle Scholar
  56. 56.
    Einstein MH, Klobocista M, Hou JY, Lee S, Mutyala S, Mehta K, et al. Phase II trial of adjuvant pelvic radiation “sandwiched” between ifosfamide or ifosfamide plus cisplatin in women with uterine carcinosarcoma. Gynecol Oncol. 2012;124(1):26–30.CrossRefPubMedGoogle Scholar
  57. 57.
    Havrilesky LJ, Secord AA, Bae-Jump V, Ayeni T, Calingaert B, Clarke-Pearson DL, et al. Outcomes in surgical stage I uterine papillary serous carcinoma. Gynecol Oncol. 2007;105(3):677–82.CrossRefPubMedGoogle Scholar
  58. 58.
    Kelly MG, O’Malley DM, Hui P, McAlpine J, Yu H, Rutherford TJ, et al. Improved survival in surgical stage I patients with uterine papillary serous carcinoma (UPSC) treated with adjuvant platinum-based chemotherapy. Gynecol Oncol. 2005;98(3):353–9.CrossRefPubMedGoogle Scholar
  59. 59.
    Fader AN, Nagel C, Axtell AE, Zanotti KM, Kelley JL, Moore KN, et al. Stage II uterine papillary serous carcinoma: carboplatin/paclitaxel chemotherapy improves recurrence and survival outcomes. Gynecol Oncol. 2009;112(3):558–62.CrossRefPubMedGoogle Scholar
  60. 60.
    Sutton G, Brunetto VL, Kilgore L, Soper JT, McGehee R, Olt G, et al. A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: a Gynecologic Oncology Group Study. Gynecol Oncol. 2000;79(2):147–53.CrossRefPubMedGoogle Scholar
  61. 61.
    Sutton G, Kauderer J, Carson LF, Lentz SS, Whitney CW, Gallion H. Adjuvant ifosfamide and cisplatin in patients with completely resected stage I or II carcinosarcomas (mixed mesodermal tumors) of the uterus: a Gynecologic Oncology Group study. Gynecol Oncol. 2005;96(3):630–4.CrossRefPubMedGoogle Scholar
  62. 62.
    Sutton G, Axelrod JH, Bundy BN, Roy T, Homesley H, Lee RB, et al. Adjuvant whole abdominal irradiation in clinical stages I and II papillary serous or clear cell carcinoma of the endometrium: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2006;100(2):349–54.CrossRefPubMedGoogle Scholar
  63. 63.
    Homesley HD, Filiaci V, Markman M, Bitterman P, Eaton L, Kilgore LC, et al. Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2007;25(5):526–31.CrossRefPubMedGoogle Scholar
  64. 64.
    The National Cancer Comprehensive Guidelines v2.2015. Uterine Neoplasms [Internet]. [cited April 21, 2015]. Available from:
  65. 65.
    Cantrell LA, Zhou C, Mendivil A, Malloy KM, Gehrig PA, Bae-Jump VL. Metformin is a potent inhibitor of endometrial cancer cell proliferation--implications for a novel treatment strategy. Gynecol Oncol. 2010;116(1):92–8.CrossRefPubMedGoogle Scholar
  66. 66.
    Hanna RK, Zhou C, Malloy KM, Sun L, Zhong Y, Gehrig PA, et al. Metformin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and modulation of the mTOR pathway. Gynecol Oncol. 2012;125(2):458–69.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Burke WM, Orr J, Leitao M, Salom E, Gehrig P, Olawaiye AB, et al. Endometrial cancer: a review and current management strategies: part II. Gynecol Oncol. 2014;134(2):393–402.CrossRefPubMedGoogle Scholar
  68. 68.
    Burke WM, Orr J, Leitao M, Salom E, Gehrig P, Olawaiye AB, et al. Endometrial cancer: a review and current management strategies: part I. Gynecol Oncol. 2014;134(2):385–92.CrossRefPubMedGoogle Scholar
  69. 69.
    Soliman PT, Oh JC, Schmeler KM, Sun CC, Slomovitz BM, Gershenson DM, et al. Risk factors for young premenopausal women with endometrial cancer. Obstet Gynecol. 2005;105(3):575–80.CrossRefPubMedGoogle Scholar
  70. 70.
    Lachance JA, Everett EN, Greer B, Mandel L, Swisher E, Tamimi H, et al. The effect of age on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer. Gynecol Oncol. 2006;101(3):470–5.CrossRefPubMedGoogle Scholar
  71. 71.
    Barakat RR, Bundy BN, Spirtos NM, Bell J, Mannel RS. Randomized double-blind trial of estrogen replacement therapy versus placebo in stage I or II endometrial cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2006;24(4):587–92.CrossRefPubMedGoogle Scholar
  72. 72.
    Ayhan A, Taskiran C, Simsek S, Sever A. Does immediate hormone replacement therapy affect the oncologic outcome in endometrial cancer survivors? Int J Gynecol Cancer. 2006;16(2):805–8.CrossRefPubMedGoogle Scholar
  73. 73.
    Lee TS, Jung JY, Kim JW, Park NH, Song YS, Kang SB, et al. Feasibility of ovarian preservation in patients with early stage endometrial carcinoma. Gynecol Oncol. 2007;104(1):52–7.CrossRefPubMedGoogle Scholar
  74. 74.
    Walsh C, Holschneider C, Hoang Y, Tieu K, Karlan B, Cass I. Coexisting ovarian malignancy in young women with endometrial cancer. Obstet Gynecol. 2005;106(4):693–9.CrossRefPubMedGoogle Scholar
  75. 75.
    Wright JD, Buck AM, Shah M, Burke WM, Schiff PB, Herzog TJ. Safety of ovarian preservation in premenopausal women with endometrial cancer. J Clin Oncol. 2009;27(8):1214–9.CrossRefPubMedGoogle Scholar
  76. 76.
    Lee TS, Kim JW, Kim TJ, Cho CH, Ryu SY, Ryu HS, et al. Ovarian preservation during the surgical treatment of early stage endometrial cancer: a nation-wide study conducted by the Korean Gynecologic Oncology Group. Gynecol Oncol. 2009;115(1):26–31.CrossRefPubMedGoogle Scholar
  77. 77.
    Kudesia R, Singer T, Caputo TA, Holcomb KM, Kligman I, Rosenwaks Z, et al. Reproductive and oncologic outcomes after progestin therapy for endometrial complex atypical hyperplasia or carcinoma. Am J Obstet Gynecol. 2014;210(3):255.CrossRefPubMedGoogle Scholar
  78. 78.
    Gallos ID, Ganesan R, Gupta JK. Prediction of regression and relapse of endometrial hyperplasia with conservative therapy. Obstet Gynecol. 2013;121(6):1165–71.CrossRefPubMedGoogle Scholar
  79. 79.
    Gill BS, Chapman BV, Hansen KJ, Sukumvanich P, Beriwal S. Primary radiotherapy for nonsurgically managed stage I endometrial cancer: utilization and impact of brachytherapy. Brachytherapy. 2015;14(3):373–9.CrossRefPubMedGoogle Scholar
  80. 80.
    Salani R, Backes FJ, Fung MF, Holschneider CH, Parker LP, Bristow RE, et al. Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations. Am J Obstet Gynecol. 2011;204(6):466–78.CrossRefPubMedGoogle Scholar
  81. 81.
    Bristow RE, Purinton SC, Santillan A, Diaz-Montes TP, Gardner GJ, Giuntoli II RL. Cost-effectiveness of routine vaginal cytology for endometrial cancer surveillance. Gynecol Oncol. 2006;103(2):709–13.CrossRefPubMedGoogle Scholar
  82. 82.
    Lajer H, Elnegaard S, Christensen RD, Ortoft G, Schledermann DE, Mogensen O. Survival after stage IA endometrial cancer; can follow-up be altered? A prospective nationwide Danish survey. Acta Obstet Gynecol Scand. 2012;91(8):976–82.CrossRefPubMedGoogle Scholar
  83. 83.
    Hunn J, Tenney ME, Tergas AI, Bishop EA, Moore K, Watkin W, et al. Patterns and utility of routine surveillance in high grade endometrial cancer. Gynecol Oncol. 2015;137(3):485–9.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Gupta D, Gunter MJ, Yang K, Lee S, Zuckerwise L, Chen LM, et al. Performance of serum CA125 as a prognostic biomarker in patients with uterine papillary serous carcinoma. Int J Gynecol Cancer. 2011;21(3):529–34.CrossRefPubMedGoogle Scholar
  85. 85.
    Olawaiye AB, Rauh-Hain JA, Withiam-Leitch M, Rueda B, Goodman A, del Carmen MG. Utility of pre-operative serum CA-125 in the management of uterine papillary serous carcinoma. Gynecol Oncol. 2008;110(3):293–8.CrossRefPubMedGoogle Scholar
  86. 86.
    Duska LR, Fader AN, Dizon DS. Survivorship in gynecologic cancer: enduring the treatment toward a new normal. Am Soc Clin Oncol Educ Book. 2014:e288–94Google Scholar
  87. 87.
    Jhingran A, Burke TW, Eifel PJ. Definitive radiotherapy for patients with isolated vaginal recurrence of endometrial carcinoma after hysterectomy. Int J Radiat Oncol Biol Phys. 2003;56(5):1366–72.CrossRefPubMedGoogle Scholar
  88. 88.
    Creutzberg CL, van Putten WL, Koper PC, Lybeert ML, Jobsen JJ, Warlam-Rodenhuis CC, et al. Survival after relapse in patients with endometrial cancer: results from a randomized trial. Gynecol Oncol. 2003;89(2):201–9.CrossRefPubMedGoogle Scholar
  89. 89.
    Barakat RR, Goldman NA, Patel DA, Venkatraman ES, Curtin JP. Pelvic exenteration for recurrent endometrial cancer. Gynecol Oncol. 1999;75(1):99–102.CrossRefPubMedGoogle Scholar
  90. 90.
    Dowdy SC, Mariani A, Cliby WA, Haddock MG, Petersen IA, Sim FH, et al. Radical pelvic resection and intraoperative radiation therapy for recurrent endometrial cancer: technique and analysis of outcomes. Gynecol Oncol. 2006;101(2):280–6.CrossRefPubMedGoogle Scholar
  91. 91.
    Rose PG, Brunetto VL, VanLe L, Bell J, Walker JL, Lee RB. A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2000;78(2):212–6.CrossRefPubMedGoogle Scholar
  92. 92.
    Fiorica J. Phase II, trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004;92(1):10–4.CrossRefPubMedGoogle Scholar
  93. 93.
    Altman AD, Thompson J, Nelson G, Chu P, Nation J, Ghatage P. Use of aromatase inhibitors as first- and second-line medical therapy in patients with endometrial adenocarcinoma: a retrospective study. J Obstet Gynaecol Can. 2012;34(7):664–72.CrossRefPubMedGoogle Scholar
  94. 94.
    Decruze SB, Green JA. Hormone therapy in advanced and recurrent endometrial cancer: a systematic review. Int J Gynecol Cancer. 2007;17(5):964–78.CrossRefPubMedGoogle Scholar
  95. 95.
    Thigpen JT, Brady MF, Alvarez RD, Adelson MD, Homesley HD, Manetta A, et al. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol. 1999;17(6):1736–44.PubMedGoogle Scholar
  96. 96.
    Dellinger TH, Monk BJ. Systemic therapy for recurrent endometrial cancer: a review of North American trials. Expert Rev Anticancer Ther. 2009;9(7):905–16.CrossRefPubMedGoogle Scholar
  97. 97.
    Thigpen T, Brady MF, Homesley HD, Soper JT, Bell J. Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2001;19(2):364–7.PubMedGoogle Scholar
  98. 98.
    Fleming GF, Brunetto VL, Cella D, Look KY, Reid GC, Munkarah AR, et al. 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(11):2159–66.CrossRefPubMedGoogle Scholar
  99. 99.
    Fleming GF, Filiaci VL, Bentley RC, Herzog T, Sorosky J, Vaccarello L, et al. Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study. Ann Oncol. 2004;15(8):1173–8.CrossRefPubMedGoogle Scholar
  100. 100.
    Humber CE, Tierney JF, Symonds RP, Collingwood M, Kirwan J, Williams C, et al. Chemotherapy for advanced, recurrent or metastatic endometrial cancer: a systematic review of Cochrane collaboration. Ann Oncol. 2007;18(3):409–20.CrossRefPubMedGoogle Scholar
  101. 101.
    Sovak MA, Dupont J, Hensley ML, Ishill N, Gerst S, Abu-Rustum N, et al. Paclitaxel and carboplatin in the treatment of advanced or recurrent endometrial cancer: a large retrospective study. Int J Gynecol Cancer. 2007;17(1):197–203.CrossRefPubMedGoogle Scholar
  102. 102.
    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(4):803–8.CrossRefPubMedGoogle Scholar
  103. 103.
    Miller DS, Blessing JA, Lentz SS, Waggoner SE. A phase II trial of topotecan in patients with advanced, persistent, or recurrent endometrial carcinoma: a gynecologic oncology group study. Gynecol Oncol. 2002;87(3):247–51.CrossRefPubMedGoogle Scholar
  104. 104.
    Moxley KM, McMeekin DS. Endometrial carcinoma: a review of chemotherapy, drug resistance, and the search for new agents. Oncologist. 2010;15(10):1026–33.CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Muggia FM, Blessing JA, Sorosky J, Reid GC. Phase II trial of the pegylated liposomal doxorubicin in previously treated metastatic endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2002;20(9):2360–4.CrossRefPubMedGoogle Scholar
  106. 106.
    Alvarez EA, Brady WE, Walker JL, Rotmensch J, Zhou XC, Kendrick JE, et al. Phase II trial of combination bevacizumab and temsirolimus in the treatment of recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2013;129(1):22–7.CrossRefPubMedGoogle Scholar
  107. 107.
    Oza AM, Elit L, Tsao MS, Kamel-Reid S, Biagi J, Provencher DM, et al. Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials Group. J Clin Oncol. 2011;29(24):3278–85.CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Myers AP. New strategies in endometrial cancer: targeting the PI3K/mTOR pathway--the devil is in the details. Clin Cancer Res. 2013;19(19):5264–74.CrossRefPubMedGoogle Scholar
  109. 109.
    Matulonis U, Vergote I, Backes F, Martin LP, McMeekin S, Birrer M, et al. Phase II study of the PI3K inhibitor pilaralisib (SAR245408; XL147) in patients with advanced or recurrent endometrial carcinoma. Gynecol Oncol. 2015;136(2):246–53.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.University of Connecticut, St. Francis Hospital & Medical Center, Comprehensive Women’s Health CenterHartfordUSA

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