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Fertility-Sparing Treatment Options in Young Patients with Early-Stage Endometrial Cancer

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Abstract

Purpose of Review

To summarize fertility-sparing treatment options in young patients with early-stage endometrial cancer.

Recent Findings

A levonorgestrel-releasing intrauterine device combined with oral progestins seems more effective for patients with endometrial cancer and desiring fertility. Assisted reproductive techniques seem more effective in achieving pregnancy in these young cancer patients than natural conception.

Summary

Endometrial cancer is the most common gynecologic cancer in developed countries. For younger patients who wish to have children, fertility preservation methods are available, but not always reasonable in an individual patient. Furthermore, fertility-preserving treatment has some risks with regard to surgical effectivity. The main criteria for fertility-sparing treatment are reproductive age of the patient, fertility desire, a grade 1 well-differentiated tumor, diagnosis should be performed through D&C, stage 1A tumor with no evidence of myometrial invasion on MRI, and no suspicious adnexal mass. A levonorgestrel-releasing intrauterine device combined with oral progestins seems more effective than using oral progestins alone. D&C should be performed every 3 months after the start of progestin therapy. Patients with two negative endometrial D&C results are considered to have a complete response and eligible for pregnancy. Hysteroscopic resection can be used in patients with grade 1 stage 1 endometrial carcinoma who did not respond to progestin treatment.

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References

    Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

    1. 1.

      Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.

    2. 2.

      Lee NK, Cheung MK, Shin JY, Husain A, Teng NN, Berek JS, et al. Prognostic factors for uterine cancer in reproductive-aged women. Obstet Gynecol. 2007;109(3):655–62.

    3. 3.

      Duska LR, Garrett A, Rueda BR, Haas J, Chang Y, Fuller AF. Endometrial cancer in women 40 years old or younger. Gynecol Oncol. 2001;83(2):388–93.

    4. 4.

      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(S8):2035–41.

    5. 5.

      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.

    6. 6.

      Li J, Zhu Q, Yang B, Ning C, Liu X, Luo X, et al. Risk factors for ovarian involvement in young and premenopausal endometrioid endometrial cancer patients. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2018;222:151–4.

    7. 7.

      Gallos ID, Yap J, Rajkhowa M, Luesley DM, Coomarasamy A, Gupta JK. Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis. American journal of obstetrics and gynecology. 2012;207(4):266. e1-. e12.

    8. 8.

      DelMaschio A, Vanzulli A, Sironi S, Spagnolo D, Belloni C, Garancini P, et al. Estimating the depth of myometrial involvement by endometrial carcinoma: efficacy of transvaginal sonography vs MR imaging. AJR Am J Roentgenol. 1993;160(3):533–8.

    9. 9.

      Yamashita Y, Mizutani H, Torashima M, Takahashi M, Miyazaki K, Okamura H, et al. Assessment of myometrial invasion by endometrial carcinoma: transvaginal sonography vs contrast-enhanced MR imaging. AJR Am J Roentgenol. 1993;161(3):595–9.

    10. 10.

      Sala E, Rockall AG, Freeman SJ, Mitchell DG, Reinhold C. The added role of MR imaging in treatment stratification of patients with gynecologic malignancies: what the radiologist needs to know. Radiology. 2013;266(3):717–40.

    11. 11.

      McEvoy SH, Nougaret S, Abu-Rustum NR, Vargas HA, Sadowski EA, Menias CO, et al. Fertility-sparing for young patients with gynecologic cancer: how MRI can guide patient selection prior to conservative management. Abdominal Radiology. 2017;42(10):2488–512.

    12. 12.

      Leitao MM Jr, Kehoe S, Barakat RR, Alektiar K, Gattoc LP, Rabbitt C, et al. Comparison of D&C and office endometrial biopsy accuracy in patients with FIGO grade 1 endometrial adenocarcinoma. Gynecol Oncol. 2009;113(1):105–8.

    13. 13.

      Dijkhuizen FPH, Mol BW, Brölmann HA, Heintz APM. The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis. Cancer. 2000;89(8):1765–72.

    14. 14.

      Feichtinger M, Rodriguez-Wallberg KA. Fertility preservation in women with cervical, endometrial or ovarian cancers. Gynecologic oncology research and practice. 2016;3(1):8.

    15. 15.

      Eskander RN, Randall LM, Berman ML, Tewari KS, Disaia PJ, Bristow RE. Fertility preserving options in patients with gynecologic malignancies. Am J Obstet Gynecol. 2011;205(2):103–10.

    16. 16.

      Park J-Y, Kim D-Y, Kim T-J, Kim JW, Kim J-H, Kim Y-M, et al. Hormonal therapy for women with stage IA endometrial cancer of all grades. Obstet Gynecol. 2013;122(1):7–14.

    17. 17.

      Hwang JY, Bae HS, Kim M-L, Jung YW, Yun BS, Seong SJ, et al. Combined oral medroxyprogesterone/levonorgestrel-intrauterine system treatment for women with grade 2 stage IA endometrial cancer. International Journal of Gynecologic Cancer. 2017;27(4):738–42.

    18. 18.

      Ruiz MP, Huang Y, Hou JY, Tergas AI, Burke WM, Ananth CV et al. All-cause mortality in young women with endometrial cancer receiving progesterone therapy. American journal of obstetrics and gynecology. 2017;217(6):669. e1-. e13.

    19. 19.

      Tewari K, Di PS. Ovulatory failure, fertility preservation and reproductive strategies in the setting of gynecologic and non-gynecologic malignancies. Eur J Gynaecol Oncol. 2006;27(5):449–61.

    20. 20.

      Decruze S, Green J. Hormone therapy in advanced and recurrent endometrial cancer: a systematic review. International Journal of Gynecologic Cancer. 2007;17(5):964–78.

    21. 21.

      Gunderson CC, Fader AN, Carson KA, Bristow RE. Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review. Gynecol Oncol. 2012;125(2):477–82.

    22. 22.

      Ramirez PT, Frumovitz M, Bodurka DC, Sun CC, Levenback C. Hormonal therapy for the management of grade 1 endometrial adenocarcinoma: a literature review. Gynecol Oncol. 2004;95(1):133–8.

    23. 23.

      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. Journal of Clinical Oncology. 1999;17(6):1736-.

    24. 24.

      Ushijima K, Yahata H, Yoshikawa H, Konishi I, Yasugi T, Saito T, et al. Multicenter phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women. J Clin Oncol. 2007;25(19):2798–803.

    25. 25.

      Kaku T, Yoshikawa H, Tsuda H, Sakamoto A, Fukunaga M, Kuwabara Y, et al. Conservative therapy for adenocarcinoma and atypical endometrial hyperplasia of the endometrium in young women: central pathologic review and treatment outcome. Cancer Lett. 2001;167(1):39–48.

    26. 26.

      Qin Y, Yu Z, Yang J, Cao D, Yu M, Wang Y, et al. Oral progestin treatment for early-stage endometrial cancer: a systematic review and meta-analysis. International Journal of Gynecologic Cancer. 2016;26(6):1081–91.

    27. 27.

      Eftekhar Z, Izadi-Mood N, Yarandi F, Shojaei H, Rezaei Z, Mohagheghi S. Efficacy of megestrol acetate (megace) in the treatment of patients with early endometrial adenocarcinoma: our experiences with 21 patients. International Journal of Gynecologic Cancer. 2009;19(2):249–52.

    28. 28.

      Koskas M, Uzan J, Luton D, Rouzier R, Daraï E. Prognostic factors of oncologic and reproductive outcomes in fertility-sparing management of endometrial atypical hyperplasia and adenocarcinoma: systematic review and meta-analysis. Fertility and sterility. 2014;101(3):785–94. e3.

    29. 29.

      Bakkum-Gamez JN, Kalogera E, Keeney GL, Mariani A, Podratz KC, Dowdy SC. Conservative management of atypical hyperplasia and grade I endometrial carcinoma: review of the literature and presentation of a series. J Gynecol Surg. 2012;28(4):262–9.

    30. 30.

      Simpson AN, Feigenberg T, Clarke BA, Gien LT, Ismiil N, Laframboise S, et al. Fertility sparing treatment of complex atypical hyperplasia and low grade endometrial cancer using oral progestin. Gynecol Oncol. 2014;133(2):229–33.

    31. 31.

      Park J-Y, Kim D-Y, Kim J-H, Kim Y-M, Kim K-R, Kim Y-T, et al. Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002). Eur J Cancer. 2013;49(4):868–74.

    32. 32.

      Montz FJ, Bristow RE, Bovicelli A, Tomacruz R, Kurman RJ. Intrauterine progesterone treatment of early endometrial cancer. Am J Obstet Gynecol. 2002;186(4):651–7.

    33. 33.

      • Gallos ID, Krishan P, Shehmar M, Ganesan R, Gupta JK. LNG-IUS versus oral progestogen treatment for endometrial hyperplasia: a long-term comparative cohort study. Human Reproduction. 2013;28(11):2966–71.This study shows the superiority of levonorgestrel-releasing intrauterine device than oral progestins.

    34. 34.

      Baker J, Obermair A, Gebski V, Janda M. Efficacy of oral or intrauterine device-delivered progestin in patients with complex endometrial hyperplasia with atypia or early endometrial adenocarcinoma: a meta-analysis and systematic review of the literature. Gynecol Oncol. 2012;125(1):263–70.

    35. 35.

      Kim MK, Seong SJ, Kim YS, Song T, Kim M-L, Yoon BS et al. Combined medroxyprogesterone acetate/levonorgestrel–intrauterine system treatment in young women with early-stage endometrial cancer. American journal of obstetrics and gynecology. 2013;209(4):358. e1-. e4.

    36. 36.

      Pronin SM, Novikova OV, Andreeva JY, Novikova EG. Fertility-sparing treatment of early endometrial cancer and complex atypical hyperplasia in young women of childbearing potential. International Journal of Gynecologic Cancer. 2015;25(6):1010–4.

    37. 37.

      Kim MK, Seong SJ, Song T, Kim M-L, Yoon BS, Jun HS, et al. Comparison of dilatation & curettage and endometrial aspiration biopsy accuracy in patients treated with high-dose oral progestin plus levonorgestrel intrauterine system for early-stage endometrial cancer. Gynecol Oncol. 2013;130(3):470–3.

    38. 38.

      Arendas K, Aldossary M, Cipolla A, Leader A, Leyland NA. Hysteroscopic resection in the management of early-stage endometrial cancer: report of 2 cases and review of the literature. J Minim Invasive Gynecol. 2015;22(1):34–9.

    39. 39.

      Laurelli G, Di Vagno G, Scaffa C, Losito S, Del Giudice M, Greggi S. Conservative treatment of early endometrial cancer: preliminary results of a pilot study. Gynecol Oncol. 2011;120(1):43–6.

    40. 40.

      Yang H-C, Liu J-C, Liu F-S. Fertility-preserving treatment of stage IA, well-differentiated endometrial carcinoma in young women with hysteroscopic resection and high-dose progesterone therapy. Taiwanese Journal of Obstetrics and Gynecology. 2019;58(1):90–3.

    41. 41.

      Chang Y-N, Zhang Y, Wang Y-J, Wang L-P, Duan H. Effect of hysteroscopy on the peritoneal dissemination of endometrial cancer cells: a meta-analysis. Fertility and sterility. 2011;96(4):957–61. e2.

    42. 42.

      Chae SH, Shim S-H, Lee SJ, Lee JY, Kim S-N, Kang S-B. Pregnancy and oncologic outcomes after fertility-sparing management for early stage endometrioid endometrial cancer. International Journal of Gynecologic Cancer. 2019;29(1):77–85.

    43. 43.

      Cramer DW. The epidemiology of endometrial and ovarian cancer. Hematology/Oncology Clinics. 2012;26(1):1–12.

    44. 44.

      Azim A, Oktay K. Letrozole for ovulation induction and fertility preservation by embryo cryopreservation in young women with endometrial carcinoma. Fertil Steril. 2007;88(3):657–64.

    45. 45.

      •• Zapardiel I, Cruz M, Diestro MD, Requena A, Garcia-Velasco JA. Assisted reproductive techniques after fertility-sparing treatments in gynaecological cancers. Human reproduction update. 2016;22(3):281–305. This study evaluates the effectivity of assisted reproductive techniques and compares the treatment options for gynecological cancers including endometrial cancer.

    46. 46.

      Oktay K, Türkçüoğlu I, Rodriguez-Wallberg KA. GnRH agonist trigger for women with breast cancer undergoing fertility preservation by aromatase inhibitor/FSH stimulation. Reprod BioMed Online. 2010;20(6):783–8.

    47. 47.

      Gressel GM, Parkash V, Pal L. Management options and fertility-preserving therapy for premenopausal endometrial hyperplasia and early-stage endometrial cancer. Int J Gynecol Obstet. 2015;131(3):234–9.

    48. 48.

      Cobo A, Garcia-Velasco JA, Domingo J, Remohí J, Pellicer A. Is vitrification of oocytes useful for fertility preservation for age-related fertility decline and in cancer patients? Fertil Steril. 2013;99(6):1485–95.

    49. 49.

      Garcia-Velasco JA, Domingo J, Cobo A, Martínez M, Carmona L, Pellicer A. Five years' experience using oocyte vitrification to preserve fertility for medical and nonmedical indications. Fertil Steril. 2013;99(7):1994–9.

    50. 50.

      Knopman JM, Noyes N, Talebian S, Krey LC, Grifo JA, Licciardi F. Women with cancer undergoing ART for fertility preservation: a cohort study of their response to exogenous gonadotropins. Fertil Steril. 2009;91(4):1476–8.

    51. 51.

      Ledda S, Leoni G, Bogliolo L, Naitana S. Oocyte cryopreservation and ovarian tissue banking. Theriogenology. 2001;55(6):1359–71.

    52. 52.

      Lotz L, Maktabi A, Hoffmann I, Findeklee S, Beckmann MW, Dittrich R. Ovarian tissue cryopreservation and retransplantation–what do patients think about it? Reprod BioMed Online. 2016;32(4):394–400.

    53. 53.

      Salama M, Woodruff TK. New advances in ovarian autotransplantation to restore fertility in cancer patients. Cancer Metastasis Rev. 2015;34(4):807–22.

    54. 54.

      Fujimoto A, Ichinose M, Harada M, Hirata T, Osuga Y, Fujii T. The outcome of infertility treatment in patients undergoing assisted reproductive technology after conservative therapy for endometrial cancer. J Assist Reprod Genet. 2014;31(9):1189–94.

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    Correspondence to Cihan Karadağ.

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    Çalışkan, E., Karadağ, C. Fertility-Sparing Treatment Options in Young Patients with Early-Stage Endometrial Cancer. Curr Obstet Gynecol Rep (2020) doi:10.1007/s13669-020-00280-2

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    Keywords

    • Assisted reproductive techniques
    • Endometrial carcinoma
    • Fertility agents, female, hormonal
    • Hysteroscopic surgery
    • Ovarian cancer