International Journal of Clinical Therapeutics and Diagnosis (IJCTD)    IJCTD-2332-2926-01-001e

Management of Endometrial Cancer



Georgios Androutsopoulos1*, Georgios Decavalas1

1.Department of Obstetrics and Gynecology, University of Patras, Medical School, Rion, Greece.

*Corresponding Author

Georgios Androutsopoulos
Department of Obstetrics and Gynecology,
University of Patras, Medical School,
Rion, Greece.
Tel: +306974088092
E-mail: androutsopoulos@upatras.gr

Article Type: Editorial
Received: October 01, 2013; Published: October 25, 2013

Citation: Androutsopoulos G, Decavalas G. (2013). Management of Endometrial Cancer, Int J Translation Community Dis, 01(1e), 01-03. doi: dx.doi.org/10.19070/2333-8385-130001e

Copyright: Androutsopoulos G© 2013. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.


Endometrial cancer (EC) is the most common malignancy of the female genital tract.1 It occurs primarily in postmenopausal women [1,2]. Overall, about 2.64% of women develop EC during their lifetime [1]. In those patients, the most common presenting symptom is abnormal uterine bleeding [2].

Based on clinical and pathological features, sporadic EC is classified into 2 types [3, 4]. Type I EC, represents the majority of sporadic EC cases (70-80%) [3,4]. It is usually well differentiated and endometrioid in histology [3, 4]. Type II EC, represents the minority of sporadic EC cases (10-20%) [3, 4]. It is poorly differentiated and usually papillary serous or clear cell in histology [3, 4].

Systematic surgical staging is the baseline therapy, for most patients with EC [2, 5-9]. Moreover, that therapeutic approach allows a more clear decision for stage related postoperative adjuvant therapy [8].

In those patients, systematic surgical staging includes: total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy and complete resection of all disease [8]. Especially in patients with type II EC, systematic surgical staging requires additional omentectomy and biopsy of any suspected lesion [10]. Pelvic washings are no longer part of FIGO surgical staging system for EC, but may be reported separately [9].

Appropriate surgical staging provides prognostic and therapeutic benefits for women with EC [2, 8]. It facilitates targeted therapy that maximize survival and minimize the morbidity of overtreatment (radiation injury) and the effects of undertreatment (recurrent disease, increased mortality) [8].

Pelvic and para-aortic lymphadenectomy is essential for surgical staging in patients with EC [5, 8]. It has diagnostic and prognostic value [5, 11]. It defines accurately the extent of disease and determines the prognosis of EC patients [5, 11]. Undoubtedly, it is the only way to identify EC patients with stage IIIc disease [8, 9, 12, 13]. Also, it provides a rationale for the need, type and extent of postoperative adjuvant treatment [5, 11, 14].

Additionally, pelvic and para-aortic lymphadenectomy seems to have a therapeutic effect in patients with EC [15-17]. It is associated with improved survival in patients with type II EC and in patients with advanced stage disease [2, 15, 16, 18, 19]. However it has no effect on survival in patients with early stage type I EC.[2, 20, 21].

It seems that pelvic and para-aortic lymphadenectomy can be safely omitted in patients with early stage well differentiated type I EC [8, 20-23]. However pelvic and para-aortic lymphadenectomy should be performed in all patients with advanced stage type I EC or with type II EC [18, 24, 25]. Also in any case of doubt, lymphadenectomy should be performed rather than abandoned [24].

The extension of pelvic and para-aortic lymph node dissection (more than 14 lymph nodes) is an independent risk factor for postoperative complications [20, 23,26]. Moreover in elderly patients and in patients with relevant comorbidities (obesity, diabetes, coronary artery disease), morbidity must be carefully weighed against any survival advantage [8, 27, 28].

Traditionally, systematic surgical staging in EC patients performed through a laparotomy [29, 30]. However in EC patients with early stage disease, it may be performed with minimally invasive techniques (laparoscopy, robotic-assisted surgery) [2, 29-32]. Minimally invasive surgery associated with smaller incisions, shorter hospital stay, quicker recovery and lower risk of complications (blood loss, wound infection, herniation and ileus) [8, 29-32]. Moreover, it offers many advantages especially in overweight and elderly patients [8, 29-33]. Compared with laparotomy, it is associated with similar overall and disease-free survival [29, 30]. However, there are relatively small differences in recurrence rates [29, 30].

Especially in EC patients at increased risk for recurrence or with advanced stage disease, required a more aggressive management with postoperative adjuvant radiotherapy and/or chemotherapy [2, 5,7, 24].

Postoperative adjuvant radiotherapy includes external pelvic radiotherapy and/or brachytherapy. Vaginal brachytherapy in EC patients with early stage disease, reduces the risk of local recurrences but has no impact on overall survival [34]. However, it is well tolerated and associated with less side effects than external pelvic radiotherapy [34]. It is the adjuvant treatment of choice for high-intermediate risk EC patients [34, 35].

External pelvic radiotherapy in EC patients with early stage disease, also reduces the risk of local recurrences but has no impact on overall survival [8, 34, 36, 37].

Also, it is associated with significant morbidity and a reduction in quality of life [34, 36]. It is used only in high risk EC patients or at advanced stage disease [35,38].

Adjuvant chemotherapy is the mainstay of treatment for EC patients with locally advanced or metastatic disease [2, 5, 39]. The most active chemotherapeutic agents are: taxanes, anthracyclines and platinum compounds [39, 40]. Although adjuvant chemotherapy achieve high response rates, it has only modest effect in progression free survival and overall survival [39].

Recent years, molecular targeted therapies have still shown modest effect in unselected EC patients [39]. They usually target the inhibition of EGFR, VEGFR and PI3K/PTEN/AKT/mTOR signal pathways [42]. Perhaps they may be clinically active as adjuvant therapy in well-defined subgroups of type II EC patients with EGFR and ErbB-2 overexpression [43, 44].


References


  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013.CA Cancer J Clin 2013;63(1):11-30.
  2. Sorosky J. Endometrial cancer. Obstet Gynecol 2012;120(2Pt 1):383-97.
  3. Bokhman J. Two pathogenetic types of endometrial carcinoma.Gynecol Oncol 1983;15(1):10-7.
  4. Doll A, Abal M, Rigau M, Monge M, Gonzalez M, DemajoS, et al. Novel molecular profiles of endometrial cancer-new light through old windows. J Steroid Biochem Mol Biol 2008;108(3-5):221-29.
  5. Bakkum-Gamez JN, Gonzalez-Bosquet J, Laack NN, Mariani A, Dowdy SC. Current issues in the management of endometrial cancer. Mayo Clin Proc 2008;83(1):97-112.
  6. Androutsopoulos G. Current treatment options in patients with endometrial cancer. J Community Med Health Educ 2012;2(12):e113.
  7. Colombo N, Preti E, Landoni F, Carinelli S, Colombo A, Marini C, et al. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2011;22(Suppl 6):vi35-9.
  8. ACOG. ACOG practice bulletin #65: management of endometrial cancer. Obstet Gynecol 2005;106(2):413-25.
  9. Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 2009;105(2):103-4.
  10. Geisler J, Geisler H, Melton M, Wiemann M. What staging surgery should be performed on patients with uterine papillary serous carcinoma? Gynecol Oncol 1999;74(3):465–7.
  11. Mariani A, Dowdy S, Cliby W, Gostout B, Jones M, Wilson T, et al. Prospective assessment of lymphatic dissemination in endometrial cancer: a paradigm shift in surgical staging. Gynecol Oncol 2008;109(1):11-8.
  12. Creasman W, Morrow C, Bundy B, Homesley H, Graham J, Heller P. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer 1987;60(8 Suppl):2035-41.
  13. McMeekin D, Lashbrook D, Gold M, Johnson G, Walker J, Mannel R. Analysis of FIGO Stage IIIc endometrial cancer patients. Gynecol Oncol 2001;81(2):273-8.
  14. Mariani A, Dowdy S, Keeney G, Long H, Lesnick T, Podratz K. High-risk endometrial cancer subgroups: candidates for target-based adjuvant therapy. Gynecol Oncol 2004;95(1):120-6.
  15. Cragun J, Havrilesky L, Calingaert B, Synan I, Secord A, Soper J, et al. Retrospective analysis of selective lymphadenectomy in apparent early-stage endometrial cancer. J Clin Oncol 2005;23(16):3668-75.
  16. Kilgore L, Partridge E, Alvarez R, Austin J, Shingleton H, Noojin F, 3rd, et al. Adenocarcinoma of the endometrium: survival comparisons of patients with and without pelvic node sampling. Gynecol Oncol 1995;56(1):29-33.
  17. Mariani A, Webb M, Galli L, Podratz K. Potential therapeutic role of para-aortic lymphadenectomy in node-positive endometrial cancer. Gynecol Oncol 2000;76(3):348-56.
  18. Lutman C, Havrilesky L, Cragun J, Secord A, Calingaert B, Berchuck A, et al. Pelvic lymph node count is an important prognostic variable for FIGO stage I and II endometrial carcinoma with high-risk histology. Gynecol Oncol 2006;102(1):92-7.
  19. Chan J, Cheung M, Huh W, Osann K, Husain A, Teng N, et al. Therapeutic role of lymph node resection in endometrioid corpus cancer: a study of 12,333 patients. Cancer 2006;107(8):1823-30.
  20. Benedetti Panici P, Basile S, Maneschi F, Alberto Lissoni A, Signorelli M, Scambia G, et al. Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. J Natl Cancer Inst 2008;100(23):1707-16.
  21. Kitchener H, Swart A, Qian Q, Amos C, Parmar M. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study. Lancet 2009;373(9658):125-36.
  22. Mariani A, Dowdy S, Podratz K. The role of pelvic and para-aortic lymph node dissection in the surgical treatment of endometrial cancer: a view from the USA. The Obstetrician & Gynaecologist 2009;11:199–204.
  23. May K, Bryant A, Dickinson H, Kehoe S, Morrison J. Lymphadenectomy for the management of endometrial cancer. Cochrane Database Syst Rev 2010(1):CD007585.
  24. Marnitz S, Kohler C. Current therapy of patients with endometrial carcinoma. A critical review. Strahlenther Onkol 2012;188(1):12-20.
  25. Nezhat F, Chang L, Solima E. What is the role of lymphadenectomy in surgical management of patients with endometrial carcinoma? J Minim Invasive Gynecol 2012;19(2):172-5.
  26. Franchi M, Ghezzi F, Riva C, Miglierina M, Buttarelli M, Bolis P. Postoperative complications after pelvic lymphadenectomy for the surgical staging of endometrial cancer. JSurg Oncol 2001;78(4):232-7; discussion 37-40.
  27. Lachance J, Darus C, Rice L. Surgical management and postoperative treatment of endometrial carcinoma. Rev Obstet Gynecol 2008;1(3):97-105.
  28. Lowery W, Gehrig P, Ko E, Secord A, Chino J, Havrilesky L. Surgical staging for endometrial cancer in the elderly- is there a role for lymphadenectomy? Gynecol Oncol2012;126(1):12-5.
  29. Galaal K, Bryant A, Fisher A, Al-Khaduri M, Kew F, Lopes A. Laparoscopy versus laparotomy for the management of early stage endometrial cancer. Cochrane Database Syst Rev 2012;9:CD006655.
  30. Walker J, Piedmonte M, Spirtos N, Eisenkop S, Schlaerth J, Mannel R, 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.
  31. Walker J, Piedmonte M, Spirtos N, Eisenkop S, Schlaerth J, Mannel R, 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.
  32. Nezhat F. Minimally invasive surgery in gynecologic oncology: laparoscopy versus robotics. Gynecol Oncol 2008;111(2 Suppl):S29-32.
  33. Fleming N, Ramirez P. Robotic surgery in gynecologic oncology. Curr Opin Oncol 2012;24(5):547-53.
  34. Kong A, Johnson N, Kitchener H, Lawrie T. Adjuvant radiotherapy for stage I endometrial cancer. Cochrane Database Syst Rev 2012(4):CD003916.
  35. Nout R, Smit V, Putter H, Jurgenliemk-Schulz I, Jobsen J,Lutgens L, et al. Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, noninferiority, randomised trial. Lancet 2010;375(9717):816-23.
  36. Creutzberg C, van Putten W, Koper P, Lybeert M, Jobsen J, Warlam-Rodenhuis C, et al. 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(9213):1404-11.
  37. Keys H, Roberts J, Brunetto V, Zaino R, Spirtos N, Bloss J, 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.
  38. Chino J, Jones E, Berchuck A, Secord A, Havrilesky L. The influence of radiation modality and lymph node dissection on survival in early-stage endometrial cancer. Int J Radiat Oncol Biol Phys 2012;82(5):1872-9.
  39. Hogberg T. What is the role of chemotherapy in endometrial cancer? Curr Oncol Rep 2011;13(6):433-41.
  40. Fleming G, Brunetto V, Cella D, Look K, Reid G, Munkarah A, 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.
  41. Schwandt A, Chen W, Martra F, Zola P, Debernardo R,Kunos C. Chemotherapy plus radiation in advanced-stage endometrial cancer. Int J Gynecol Cancer 2011;21(9):1622- 7.
  42. Dedes K, Wetterskog D, Ashworth A, Kaye S, Reis-Filho J. Emerging therapeutic targets in endometrial cancer. Nat Rev Clin Oncol 2011;8(5):261-71.
  43. Konecny G, Santos L, Winterhoff B, Hatmal M, Keeney GL, Mariani A, et al. HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer. Br J Cancer 2009;100(1):89-95.
  44. Androutsopoulos G, Adonakis G, Liava A, Ravazoula P, Decavalas G. Expression and potential role of ErbB receptors in type II endometrial cancer. Eur J Obstet Gynecol Reprod Biol 2013;168(2):204-8.

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