ISSN: 2377-4304OGIJ

Obstetrics & Gynecology International Journal
Editorial
Volume 2 Issue 2 - 2015
Present and Future in Endometrial Cancer Treatment
Georgios Androutsopoulos*, Georgios Adonakis and Georgios Decavalas
Department of Obstetrics and Gynecology, University of Patras, Greece
Received: March 14, 2015 | Published: April 08, 2015
*Corresponding author: Georgios Androutsopoulos, Assistant Professor, Department of Obstetrics and Gynecology, University of Patras, Medical School, Rion 26504, Greece, Tel: +306974088092; Email: @, @
Citation: Androutsopoulos G, Adonakis G, Decavalas G (2015) Present and Future in Endometrial Cancer Treatment. Obstet Gynecol Int J 2(2): 00031. DOI: 10.15406/ogij.2015.02.00031

Editorial

In the developed world, endometrial cancer (EC) is the most frequent female genital tract malignancy [1-5]. The lifetime risk of developing EC is 2.64% [1]. It most commonly occurs in postmenopausal women [1-5]. Moreover based on its clinical and pathological features, sporadic EC classified into 2 types (type I EC and type II EC) [6,7].

According to ACOG, FIGO, SGO and ESMO recommendations, systematic surgical staging is the primary treatment for EC patients [3-5,8-12]. Especially in patients with type I EC (endometrioid), systematic surgical staging includes: total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy and complete resection of all disease [2-5,8-13]. However in patients with type II EC (poorly differentiated, papillary serous, clear cell), systematic surgical staging includes: total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy and additional omentectomy, appendectomy and biopsy of any suspected lesion [3-5,10,11,14]. Positive pelvic washings should be reported separately, although they do not affect FIGO staging for EC [9].

Laparotomy is the preferable surgical technique for systematic surgical staging in most EC patients [3-5,10,11,15,16]. However in EC patients with early stage disease, we can also use minimally invasive techniques (laparoscopy, robotic-assisted surgery) for the same purpose [2-5,8,10-12,15-18].

It is widely accepted that minimally invasive techniques have many significant advantages (smaller incisions, improved visualization, shorter hospital stay, less need for analgesics, quicker recovery and lower risk of postoperative complications) [3-5,8,10-12,15-19]. Those advantages are very important, especially in overweight and elderly patients [3-5,8,10-12,15-19].

The various surgical techniques (laparotomy, minimally invasive techniques) that applied in EC patients, have relatively small differences in recurrence rates [15,16]. Moreover, those surgical techniques (laparotomy, minimally invasive techniques) associated with similar overall and disease-free survival rates [10,12,15,16].

It should be mentioned that pelvic and para-aortic lymphadenectomy, are absolutely necessary in EC patients for the diagnosis of stage IIIc disease [3-5,8,9,11-13,20,21]. Moreover the application of pelvic and para-aortic lymphadenectomy in patients with advanced stage type I EC and in all patients with type II EC, associated with improved survival [2-5,11,22-26]. However the application of pelvic and para-aortic lymphadenectomy in patients with early stage type I EC, do not improve survival [2-5,11,12,27,28].

Moreover the extent of pelvic and para-aortic lymphadenectomy (>14 lymph nodes), increases significantly the risk for postoperative complications [3-5,11,27,29,30]. Especially in elderly patients and in patients with relative comorbidities (obesity, diabetes, coronary artery disease), pelvic and para-aortic lymphadenectomy increases significantly the intraoperative and postoperative morbidity [3-5,8,11,29,31,32]. In any case, the intraoperative and postoperative morbidity must be carefully weighed against any survival advantage [3-5,11,29,31,32].

It is obvious that the application of systematic surgical staging in EC patients, has diagnostic, prognostic and therapeutic benefits [2-5,8,11]. Moreover, systematic surgical staging allows a more clear decision for the selection of the appropriate postoperative adjuvant treatment [3-5,8,11]. Additionally, the application of the appropriate postoperative adjuvant treatment maximize survival and minimize the morbidity of overtreatment (radiation injury) and the effects of undertreatment (recurrent disease, increased mortality) [3-5,8,11].

However according to ACOG, SGO and ESMO recommendations, the application of postoperative adjuvant treatment (radiotherapy and/or chemotherapy) is absolutely necessary, particularly in EC patients with increased risk for recurrence or at advanced stage disease [2-5,8,10,13,33,34]. More specifically, the application of postoperative adjuvant radiotherapy in EC patients includes vaginal brachytherapy and external radiotherapy [3-5,10,11,34].

Vaginal brachytherapy is the adjuvant treatment of choice particularly in intermediate risk EC patients (stage IA grade 3 endometrioid type EC, stage IB grade 1-2 endometrioid type EC) [3-5,10,11,34-39]. It is well tolerated, reduces the risk for local recurrences but has no impact on overall survival [34,35,38,40]. Moreover, the application of vaginal brachytherapy associated with less side effects and better quality of life [10,34-38,40]. Additionally in intermediate risk EC patients, the application of vaginal brachytherapy is equivalent to the application of external pelvic radiotherapy in achieving local control of disease [3-5,10,11,34-37].

External pelvic radiotherapy is the adjuvant treatment of choice particularly in high risk EC patients (stage IB grade 3 endometrioid type EC, stage I non-endometrioid type EC) [3-5,10,11,36,37,40]. Although it reduces the risk for local recurrences, it has no impact on overall survival [3-5,8,34-36,38,41,42]. However, the application of external pelvic radiotherapy associated with significant morbidity and reduction in quality of life [3-5,11,35,41].

Whole abdomen radiotherapy can be used in EC patients with advanced stage disease [43]. However, it can be used only in patients with completely resected disease [43]. Moreover, the application of whole abdomen radiotherapy has tolerable toxicity and may improve overall survival [3-5,11,43].

Postoperative adjuvant chemotherapy is the adjuvant treatment of choice particularly in EC patients with advanced stage disease [2-5,10,11,13,34,44,45]. The most active chemotherapeutic agents for those EC patients, are: taxanes, anthracyclines and platinum compounds [44,46]. Although the application of adjuvant chemotherapy achieves high response rates, it has only modest effect in progression free survival and overall survival [3-5,11,44]. Moreover, the application of adjuvant chemotherapy is more effective than the application of whole abdomen radiotherapy [3-5,11,33,47].

Combined application of adjuvant chemotherapy and radiotherapy is a promising adjuvant treatment particularly in high risk EC patients and in EC patients at advanced stage disease [3-5,11,34,44,48]. Especially in EC patients with completely resected disease, the combined application of adjuvant chemotherapy and radiotherapy significantly reduce the risk of relapse or death and increase overall survival [3-5,10,11,34,49]. Moreover, the combined application of adjuvant chemotherapy and radiotherapy is more effective than the application of adjuvant radiotherapy alone [3-5,11,34,44,49].

Recent years, molecular targeted therapies have increasing popularity [3-5,11]. However, they have only modest effect in unselected EC patients [3-5,11,44,50-53]. Moreover the application of molecular targeted therapies, usually target the signaling pathways of EGFR, VEGFR and PI3K/PTEN/AKT/Mtor [54-56]. More specifically, ErbB-targeted therapies can be used as adjuvant treatment especially in type II EC patients with EGFR and ErbB-2 overexpression [3-5,11,50-53,56-63]. However, additional studies into the molecular pathways of EC are necessary [3-5,11,50-52,62,63].

It is obvious that the present and future in endometrial cancer treatment is extremely challenging, especially regarding the application of postoperative adjuvant treatment in EC patients with increased risk for recurrence or at advanced stage disease.

References

  1. Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63(1): 11-30.
  2. Sorosky J (2012) Endometrial cancer. Obstet Gynecol 120(2 Pt 1): 383-397.
  3. Androutsopoulos G (2012) Current treatment options in patients with endometrial cancer. J Community Med Health Educ 2(12): e113.
  4. Androutsopoulos G, Decavalas G (2013) Management of endometrial cancer. Int J Translation Community Dis 1(1): 1-3.
  5. Androutsopoulos G, Michail G, Adonakis G, Decavalas G (2015) Current treatment approach of endometrial cancer. Int J Clin Ther Diagn S1(3): 8-11.
  6. Bokhman J (1983) Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 15(1): 10-17.
  7. Doll A, Abal M, Rigau M, Monge M, Gonzalez M, et al. (2008) Novel molecular profiles of endometrial cancer-new light through old windows. J Steroid Biochem Mol Biol 108(3-5): 221-229.
  8. American College of Obstetricians and Gynecologists (2005) ACOG practice bulletin #65: management of endometrial cancer. Obstet Gynecol 106(2): 413-425.
  9. Pecorelli S (2009) Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 105(2): 103-134.
  10. Colombo N, Preti E, Landoni F, Carinelli S, Colombo A, et al. (2013) Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 24(Suppl 6): 33-38.
  11. Androutsopoulos G, Decavalas G (2014) Endometrial cancer: current treatment strategies. World J Oncol Res 1(1): 1-4.
  12. Burke W, Orr J, Leitao M, Salom E, Gehrig P, et al. (2014) Endometrial cancer: a review and current management strategies: part I. Gynecol Oncol 134(2): 385-392.
  13. Bakkum-Gamez JN, Gonzalez-Bosquet J, Laack NN, Mariani A, Dowdy SC (2008) Current issues in the management of endometrial cancer. Mayo Clin Proc 83(1): 97-112.
  14. Geisler J, Geisler H, Melton M, Wiemann M (1999) What staging surgery should be performed on patients with uterine papillary serous carcinoma? Gynecol Oncol 74(3): 465-467.
  15. Galaal K, Bryant A, Fisher A, Al-Khaduri M, Kew F, et al. (2012) Laparoscopy versus laparotomy for the management of early stage endometrial cancer. Cochrane Database Syst Rev 9: CD006655.
  16. Walker J, Piedmonte M, Spirtos N, Eisenkop S, Schlaerth J, et al. (2012) 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 30(7): 695-700.
  17. Walker J, Piedmonte M, Spirtos N, Eisenkop S, Schlaerth J, et al. (2009) Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group Study LAP2. J Clin Oncol 27(32): 5331-5336.
  18. Nezhat F (2008) Minimally invasive surgery in gynecologic oncology: laparoscopy versus robotics. Gynecol Oncol 111(2 Suppl): S29-32.
  19. Fleming N, Ramirez P (2012) Robotic surgery in gynecologic oncology. Curr Opin Oncol 24(5): 547-553.
  20. Creasman W, Morrow C, Bundy B, Homesley H, Graham J, et al. (1987) Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer 60(8 Suppl): 2035-2041.
  21. McMeekin D, Lashbrook D, Gold M, Johnson G, Walker J, et al. (2001) Analysis of FIGO Stage IIIc endometrial cancer patients. Gynecol Oncol 81(2): 273-278.
  22. Kilgore L, Partridge E, Alvarez R, Austin J, Shingleton H, et al. (1995) Adenocarcinoma of the endometrium: survival comparisons of patients with and without pelvic node sampling. Gynecol Oncol 56(1): 29-33.
  23. Cragun J, Havrilesky L, Calingaert B, Synan I, Secord A, et al. (2005) Retrospective analysis of selective lymphadenectomy in apparent early-stage endometrial cancer. J Clin Oncol 23(16): 3668-3675.
  24. Lutman C, Havrilesky L, Cragun J, Secord A, Calingaert B, et al. (2006) Pelvic lymph node count is an important prognostic variable for FIGO stage I and II endometrial carcinoma with high-risk histology. Gynecol Oncol 102(1): 92-97.
  25. Chan J, Cheung M, Huh W, Osann K, Husain A, et al. (2006) Therapeutic role of lymph node resection in endometrioid corpus cancer: a study of 12,333 patients. Cancer 107(8): 1823-1830.
  26. Mariani A, Webb M, Galli L, Podratz K (2000) Potential therapeutic role of para-aortic lymphadenectomy in node-positive endometrial cancer. Gynecol Oncol 76(3): 348-356.
  27. Benedetti Panici P, Basile S, Maneschi F, Alberto Lissoni A, Signorelli M, 7 et al. () Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. J Natl Cancer Inst 100(23): 1707-1716.
  28. Kitchener H, Swart A, Qian Q, Amos C, Parmar M (2009) Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study. Lancet 373(9658):125-136.
  29. Franchi M, Ghezzi F, Riva C, Miglierina M, Buttarelli M, et al. (2001) Postoperative complications after pelvic lymphadenectomy for the surgical staging of endometrial cancer. J Surg Oncol 78(4): 232-237; discussion 37-40.
  30. May K, Bryant A, Dickinson H, Kehoe S, Morrison J (2010) Lymphadenectomy for the management of endometrial cancer. Cochrane Database Syst Rev (1): CD007585.
  31. Lachance J, Darus C, Rice L (2008) Surgical management and postoperative treatment of endometrial carcinoma. Rev Obstet Gynecol 1(3): 97-105.
  32. Lowery W, Gehrig P, Ko E, Secord A, Chino J, et al. (2012) Surgical staging for endometrial cancer in the elderly - is there a role for lymphadenectomy? Gynecol Oncol 126(1): 12-15.
  33. Marnitz S, Kohler C (188) Current therapy of patients with endometrial carcinoma. A critical review. Strahlenther Onkol 188(1): 12-20.
  34. Burke W, Orr J, Leitao M, Salom E, Gehrig P, et al. (2014) Endometrial cancer: a review and current management strategies: part II. Gynecol Oncol 134(2): 393-402.
  35. Kong A, Johnson N, Kitchener H, Lawrie T (2012) Adjuvant radiotherapy for stage I endometrial cancer. Cochrane Database Syst Rev 3: CD003916.
  36. Nout R, Smit V, Putter H, Jurgenliemk-Schulz I, Jobsen J, et al. (2010) 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 375(9717): 816-823.
  37. Chino J, Jones E, Berchuck A, Secord A, Havrilesky L (2012) The influence of radiation modality and lymph node dissection on survival in early-stage endometrial cancer. Int J Radiat Oncol Biol Phys 82(5): 1872-1879.
  38. Creutzberg C, Nout R (2011) The role of radiotherapy in endometrial cancer: current evidence and trends. Curr Oncol Rep 13(6): 472-478.
  39. Sorbe B, Horvath G, Andersson H, Boman K, Lundgren C, et al. (2012) External pelvic and vaginal irradiation versus vaginal irradiation alone as postoperative therapy in medium-risk endometrial carcinoma: a prospective, randomized study--quality-of-life analysis. Int J Gynecol Cancer 22(7): 1281-1288.
  40. Creutzberg C (2004) GOG-99: ending the controversy regarding pelvic radiotherapy for endometrial carcinoma? Gynecol Oncol 92(3): 740-743.
  41. Creutzberg C, van Putten W, Koper P, Lybeert M, Jobsen J, et al. (2000) 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 355(9213): 1404-1411.
  42. Keys H, Roberts J, Brunetto V, Zaino R, Spirtos N, et al. (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.
  43. Sutton G, Axelrod J, Bundy B, Roy T, Homesley H, et al. (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.
  44. Hogberg T (2011) What is the role of chemotherapy in endometrial cancer? Curr Oncol Rep 13(6): 433-441.
  45. Wright J, Barrena Medel N, Sehouli J, Fujiwara K, Herzog T (2012) Contemporary management of endometrial cancer. Lancet 379(9823): 1352-1360.
  46. Fleming G, Brunetto V, Cella D, Look K, Reid G, et al. (2004) 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 22(11): 2159-2166.
  47. Randall M, Filiaci V, Muss H, Spirtos N, Mannel R, et al. (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.
  48. Schwandt A, Chen W, Martra F, Zola P, Debernardo R, et al. (2011) Chemotherapy plus radiation in advanced-stage endometrial cancer. Int J Gynecol Cancer 21(9): 1622-1627.
  49. Hogberg T, Signorelli M, de Oliveira C, Fossati R, Lissoni A, et al. (2010) Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer--results from two randomised studies. Eur J Cancer 46(13): 2422-2431.
  50. Adonakis G, Androutsopoulos G (2012) The role of ErbB receptors in endometrial cancer. In: Saldivar J (Ed.) Cancer of the uterine endometrium - advances and controversies: InTech pp. 23-38.
  51. Androutsopoulos G, Adonakis G, Decavalas G (2014) ErbB targeted therapy in endometrial cancer. In: Farghaly S (Ed.) Endometrial cancer: current epidemiology, detection and management. Nova Science Publishers, Hauppauge, NY, USA, pp. 353-370.
  52. Androutsopoulos G, Adonakis G, Liava A, Ravazoula P, Decavalas G (2013) Expression and potential role of ErbB receptors in type II endometrial cancer. Eur J Obstet Gynecol Reprod Biol 168(2): 204-208.
  53. Androutsopoulos G, Michail G, Adonakis G, Decavalas G (2014) ErbB receptors and ErbB targeted therapies in endometrial cancer. J Cancer Ther 5(6): 483-492.
  54. Dedes K, Wetterskog D, Ashworth A, Kaye S, Reis-Filho J (2011) Emerging therapeutic targets in endometrial cancer. Nat Rev Clin Oncol 8(5): 261-271.
  55. Tsoref D, Oza AM (2011) Recent advances in systemic therapy for advanced endometrial cancer. Curr Opin Oncol 23(5): 494-500.
  56. Kieser K, Oza A (2005) What's new in systemic therapy for endometrial cancer. Curr Opin Oncol 17(5): 500-504.
  57. Konecny G, Santos L, Winterhoff B, Hatmal M, Keeney GL, et al. (2009) HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer. Br J Cancer 100(1): 89-95.
  58. Santin A, Bellone S, Roman J, McKenney J, Pecorelli S (2008) Trastuzumab treatment in patients with advanced or recurrent endometrial carcinoma overexpressing HER2/neu. Int J Gynaecol Obstet 102(2): 128-31.
  59. Oza A, Eisenhauer E, Elit L, Cutz J, Sakurada A, et al. (2008) Phase II study of erlotinib in recurrent or metastatic endometrial cancer: NCIC IND-148. J Clin Oncol 26(26): 4319-4325.
  60. Fleming G, Sill M, Darcy K, McMeekin D, Thigpen J, et al. (2010) Phase II trial of trastuzumab in women with advanced or recurrent, HER2-positive endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 116(1): 15-20.
  61. Roque D, Santin A (2013) Updates in therapy for uterine serous carcinoma. Curr Opin Obstet Gynecol 25(1): 29-37.
  62. Adonakis G, Androutsopoulos G, Koumoundourou D, Liava A, Ravazoula P, et al. (2008) Expression of the epidermal growth factor system in endometrial cancer. Eur J Gynaecol Oncol 29(5): 450-454.
  63. Androutsopoulos G, Adonakis G, Gkermpesi M, Gkogkos P, Ravazoula P, et al. (2006) Expression of the epidermal growth factor system in endometrial cancer after adjuvant tamoxifen treatment for breast cancer. Eur J Gynaecol Oncol 27(5): 490-494.
© 2014-2016 MedCrave Group, All rights reserved. No part of this content may be reproduced or transmitted in any form or by any means as per the standard guidelines of fair use.
Creative Commons License Open Access by MedCrave Group is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work at http://medcraveonline.com
Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version | Opera |Privacy Policy