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Surgical treatment of high stage endometrial cancer: current perspectives

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Endometrial cancer is now the most common gynecologic malignancy. We investigate on new scientific evidences in endometrial cancer, particularly underlined updates in advanced endometrial cancer. Early stage endometrial cancer is the most frequent presentation; however, advanced endometrial cancer that occurs in 3–13 % of cases has bad prognosis. There are two types of endometrial cancer different in molecular pattern, therapeutic strategy and prognosis. Type I endometrial cancers develop in an environment of unopposed estrogen and often arise out of endometrial hyperplasia, characterized by mutations in the PTEN gene, K-ras, and microsatellite instability inception. Type II cancer is not an estrogen-related cancer, occurs predominantly in postmenopausal women, shows typical mutations in p53 and HER2/neu and has a poor prognosis. Preoperative characterization of the type’s disease is an essential step for a right diagnosis and treatment. All patients should undergo to surgical staging, except those who are inoperable, according to FIGO recommendation. Surgical debulking, neoadjuvant chemotherapy and interval debulking can be strategy options.

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  1. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60(5):277–300. doi:10.3322/caac.20073

    Article  PubMed  Google Scholar 

  2. Ueda SM, Kapp DS, Cheung MK, Shin JY, Osann K, Husain A, Teng NN, Berek JS, Chan JK (2008) Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths. Am J Obstet Gynecol 198(2):218.e1–6. doi:10.1016/j.ajog.2007.08.075

    Article  PubMed  Google Scholar 

  3. Thigpen JT, Brady MF, Alvarez RD, Adelson MD, Homesley HD, Manetta A, Soper JT, Given FT (1999) Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose–response study by the Gynecologic Oncology Group. J Clin Oncol 17(6):1736–1744

    CAS  PubMed  Google Scholar 

  4. Lentz SS, Brady MF, Major FJ, Reid GC, Soper JT (1996) High-dose megestrol acetate in advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 14(2):357–361

    CAS  PubMed  Google Scholar 

  5. Whitney CW, Brunetto VL, Zaino RJ, Lentz SS, Sorosky J, Armstrong DK, Lee RB, Gynecologic Oncology Group Study (2004) Phase II study of medroxyprogesterone acetate plus tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. Gynecol Oncol 92(1):4–9

    Article  CAS  PubMed  Google Scholar 

  6. Pliskow S, Penalver M, Averette HE (1990) Stage III and stage IV endometrial carcinoma: a review of 41 cases. Gynecol Oncol 38(2):210–215

    Article  CAS  PubMed  Google Scholar 

  7. Keys HM, Roberts JA, Brunetto VL, Zaino RJ, Spirtos NM, Bloss JD, Pearlman A, Maiman MA, Bell JG, Gynecologic Oncology Group (2004) 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 92(3):744–751. doi:10.1016/j.ygyno.2003.11.048

    Article  PubMed  Google Scholar 

  8. Sutton G, Axelrod JH, Bundy BN, Roy T, Homesley HD, Malfetano JH, Mychalczak BR, King ME (2005) Whole abdominal radiotherapy in the adjuvant treatment of patients with stage III and IV endometrial cancer: a Gynecologic Oncology Group Study. Gynecol Oncol 97(3):755–763. doi:10.1016/j.ygyno.2005.03.011

    Article  PubMed  Google Scholar 

  9. Randall ME, Filiaci VL, Muss H, Spirtos NM, Mannel RS, Fowler J, Thigpen JT, Benda JA, Gynecologic Oncology Group Study (2006) 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 24(1):36–44. doi:10.1200/JCO.2004.00.7617

    Article  CAS  PubMed  Google Scholar 

  10. Goff BA, Goodman A, Muntz HG, Fuller AF Jr, Nikrui N, Rice LW (1994) Surgical stage IV endometrial carcinoma: a study of 47 cases. Gynecol Oncol 52(2):237–240. doi:10.1006/gyno.1994.1038

    Article  CAS  PubMed  Google Scholar 

  11. Chi DS, Welshinger M, Venkatraman ES, Barakat RR (1997) The role of surgical cytoreduction in stage IV endometrial carcinoma. Gynecol Oncol 67(1):56–60. doi:10.1006/gyno.1997.4838

    Article  CAS  PubMed  Google Scholar 

  12. Bristow RE, Zerbe MJ, Rosenshein NB, Grumbine FC, Montz FJ (2000) Stage IVB endometrial carcinoma: the role of cytoreductive surgery and determinants of survival. Gynecol Oncol 78(2):85–91. doi:10.1006/gyno.2000.5843

    Article  CAS  PubMed  Google Scholar 

  13. Ayhan A, Taskiran C, Celik C, Yuce K, Kucukali T (2002) The influence of cytoreductive surgery on survival and morbidity in stage IVB endometrial cancer. Int J Gynecol Cancer 12(5):448–453

    Article  CAS  PubMed  Google Scholar 

  14. Lambrou NC, Gomez-Marin O, Mirhashemi R, Beach H, Salom E, Almeida-Parra Z, Penalver M (2004) Optimal surgical cytoreduction in patients with stage III and stage IV endometrial carcinoma: a study of morbidity and survival. Gynecol Oncol 93(3):653–658. doi:10.1016/j.ygyno.2004.03.015

    Article  PubMed  Google Scholar 

  15. Wiseman M (2008) The second World Cancer Research Fund/American Institute for Cancer Research expert report. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Proc Nutr Soc 67(3):253–256. doi:10.1017/S002966510800712X

    Article  PubMed  Google Scholar 

  16. Reeves GK, Pirie K, Beral V, Green J, Spencer E, Bull D, Million Women Study (2007) Cancer incidence and mortality in relation to body mass index in the Million Women Study: Cohort Study. BMJ 335(7630):1134. doi:10.1136/bmj.39367.495995.AE

    Article  PubMed  PubMed Central  Google Scholar 

  17. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371(9612):569–578. doi:10.1016/S0140-6736(08)60269-X

    Article  PubMed  Google Scholar 

  18. Nead KT, Sharp SJ, Thompson DJ, Painter JN, Savage DB, Semple RK, Barker A, Australian National Endometrial Cancer Study Group, Perry JR, Attia J, Dunning AM, Easton DF, Holliday E, Lotta LA, O’Mara T, McEvoy M, Pharoah PD, Scott RJ, Spurdle AB, Langenberg C, Wareham NJ, Scott RA (2015) Evidence of a causal association between insulinemia and endometrial cancer: a Mendelian randomization analysis. J Natl Cancer Inst. doi:10.1093/jnci/djv178

    PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  20. Schmandt RE, Iglesias DA, Co NN, Lu KH (2011) Understanding obesity and endometrial cancer risk: opportunities for prevention. Am J Obstet Gynecol 205(6):518–525. doi:10.1016/j.ajog.2011.05.042

    Article  PubMed  PubMed Central  Google Scholar 

  21. Mitsuhashi A, Kiyokawa T, Sato Y, Shozu M (2014) Effects of metformin on endometrial cancer cell growth in vivo: a preoperative prospective trial. Cancer 120(19):2986–2995. doi:10.1002/cncr.28853

    Article  CAS  PubMed  Google Scholar 

  22. Vincent HK, Taylor AG (2006) Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans. Int J Obes 30(3):400–418. doi:10.1038/sj.ijo.0803177

    Article  CAS  Google Scholar 

  23. Ivanova TI, Krikunova LI, Ryabchenko NI, Mkrtchyan LS, Khorokhorina VA, Salnikova LE (2015) Association of the apolipoprotein E 2 allele with concurrent occurrence of endometrial hyperplasia and endometrial carcinoma. Oxid Med Cell Longev 2015:593658. doi:10.1155/2015/593658

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ferguson SE, Soslow RA, Amsterdam A, Barakat RR (2006) Comparison of uterine malignancies that develop during and following tamoxifen therapy. Gynecol Oncol 101(2):322–326. doi:10.1016/j.ygyno.2005.10.026

    Article  CAS  PubMed  Google Scholar 

  25. Di Cello A, Rania E, Zuccala V, Venturella R, Mocciaro R, Zullo F, Morelli M (2015) Failure to recognize preoperatively high-risk endometrial carcinoma is associated with a poor outcome. Eur J Obstet Gynecol Reprod Biol 194:153–160. doi:10.1016/j.ejogrb.2015.09.004

    Article  PubMed  Google Scholar 

  26. Westin SN, Broaddus RR (2012) Personalized therapy in endometrial cancer: challenges and opportunities. Cancer Biol Ther 13(1):1–13. doi:10.4161/cbt.13.1.18438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tafe LJ (2015) Targeted next-generation sequencing for hereditary cancer syndromes: a focus on Lynch syndrome and associated endometrial cancer. J Mol Diagn 17(5):472–482. doi:10.1016/j.jmoldx.2015.06.001

    Article  CAS  PubMed  Google Scholar 

  28. Denschlag D, Ulrich U, Emons G (2010) The diagnosis and treatment of endometrial cancer: progress and controversies. Dtsch Arztebl Int 108(34–35):571–577. doi:10.3238/arztebl.2011.0571

    PubMed  Google Scholar 

  29. Mariani A, Dowdy SC, Cliby WA, Gostout BS, Jones MB, Wilson TO, Podratz KC (2008) Prospective assessment of lymphatic dissemination in endometrial cancer: a paradigm shift in surgical staging. Gynecol Oncol 109(1):11–18. doi:10.1016/j.ygyno.2008.01.023

    Article  PubMed  PubMed Central  Google Scholar 

  30. Landrum LM, Moore KN, Myers TK, Lanneau GS Jr, McMeekin DS, Walker JL, Gold MA (2009) Stage IVB endometrial cancer: does applying an ovarian cancer treatment paradigm result in similar outcomes? A case–control analysis. Gynecol Oncol 112(2):337–341. doi:10.1016/j.ygyno.2008.10.009

    Article  PubMed  Google Scholar 

  31. Barlin JN, Puri I, Bristow RE (2010) Cytoreductive surgery for advanced or recurrent endometrial cancer: a meta-analysis. Gynecol Oncol 118(1):14–18. doi:10.1016/j.ygyno.2010.04.005

    Article  PubMed  Google Scholar 

  32. Thomas MB, Mariani A, Cliby WA, Keeney GL, Podratz KC, Dowdy SC (2007) Role of cytoreduction in stage III and IV uterine papillary serous carcinoma. Gynecol Oncol 107(2):190–193. doi:10.1016/j.ygyno.2007.05.039

    Article  PubMed  Google Scholar 

  33. Vergote I, Trope CG, Amant F, Kristensen GB, Ehlen T, Johnson N, Verheijen RH, van der Burg ME, Lacave AJ, Panici PB, Kenter GG, Casado A, Mendiola C, Coens C, Verleye L, Stuart GC, Pecorelli S, Reed NS, European Organization for R, Treatment of Cancer-Gynaecological Cancer G, Group NCT (2010) Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 363(10):943–953. doi:10.1056/NEJMoa0908806

    Article  CAS  PubMed  Google Scholar 

  34. Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM, Baergen R, Gynecologic Oncology G (2003) Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 21(17):3194–3200. doi:10.1200/JCO.2003.02.153

    Article  CAS  PubMed  Google Scholar 

  35. Einstein MH, Rice LW (2012) Current surgical management of endometrial cancer. Hematol Oncol Clin North Am 26(1):79–91. doi:10.1016/j.hoc.2011.10.005 (Epub 2011 Nov 21)

    Article  PubMed  Google Scholar 

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Correspondence to Salvatore Giovanni Vitale.

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Vitale, S.G., Valenti, G., Gulino, F.A. et al. Surgical treatment of high stage endometrial cancer: current perspectives. Updates Surg 68, 149–154 (2016).

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