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Fertility-preserving Management of Endometrial Carcinoma
European Oncology & Haematology, 2011;7(3):191-5
AbstractEndometrial cancer is the most common gynaecological malignancy, usually diagnosed in post-menopausal women. However, an incidence of 2–14 % of cases occurring in women <45 years of age has been reported. In this group of younger patients, because of the childbearing challenges, there is an increased percentage of nulliparity. Due to the early disease stage and the low grade of differentiation at the time of diagnosis, an improved prognosis has been reported in this group of patients. Many reports have described conservative treatment of this tumour in selected patients with the aim of preserving fertility. In this article, we review the literature for a better assessment of selection criteria, risk of concomitant neoplasias, hormonal treatment and clinical and reproductive outcome. We have concluded that fertility-preserving management of endometrial cancer is feasible in selected patients with an acceptable clinical and reproductive outcome.
Keywords: Endometrial carcinoma, conservative treatment, fertility sparing, young patients
Disclosure: The authors have no conflicts of interest to declare.
Received: October 08, 2010 Accepted January 14, 2011 Citation European Oncology & Haematology, 2011;7(3):191-5
Correspondence: Sonsoles Alonso, MD Anderson International Spain, C/ Arturo Soria 270, 28033 Madrid, Spain. E: firstname.lastname@example.org
Endometrial cancer is the most common gynaecological malignancy. The five-year survival rate is excellent: 84.3 % in Spain for all stages with complete treatment.1 The International Federation of Gynecology and Obstetrics (FIGO) stage is the independent criterion that best indicates the prognosis of this tumour. In the last FIGO Annual Report the five-year survival rate for surgical stage I was 90 %.2
In this article, we examine whether preserving fertility is a safe therapeutic option in selected cases of young women with endometrial cancer. We evaluate the characteristics of these young patients, selection of criteria and related problems, diverse treatment regimens, follow-up and reproductive outcome, using the evidence present in the literature. We consider young patients as those <45 years of age. Usually, diagnosis of endometrial cancer occurs in post-menopausal women after their sixth decade, with an average age of 61 to 64 years of age, depending on the series. The hormonal status of patients shows that only 11 % are pre-menopausal when diagnosed.1
Although it is uncommon in young patients, this malignancy is diagnosed in about 2–14 % of women ≥45 years of age. This broad age range is the reason for the variance in cut-off points for young patients in the different series. We diagnose this malignancy in women who have not borne children, and due to the challenge of childbirth, conservative treatment has been discussed in recent years as a safe therapeutic option for these patients. The current evidence is insufficient, but increasingly becoming more available via recent prospective studies and meta-analyses.
Characteristics of Young Patients
For a better assessment of selection criteria for conservative treatment, we consider different population characteristics. This is an initial point in recognising the behaviour of endometrial cancer in young women. The median age at diagnosis in this group of young women is 40 (range 31–45 years of age).
33,4 causing delay and making diagnosis a more difficult task, which sometimes accounts for the confusion with dysfunctional uterine bleeding.
We reported an increased percentage of sterility and nulliparity (61 % of patients <45 years of age were nulliparous versus 24 % in the older group).5 These results are even lower than those reported by other physicians, such as Navarria et al., who found a 79 % incidence of nulliparous patients.6 Other authors have accounted for an increased incidence of endometrial cancer in patients with other hormonal disorders related to an excessive oestrogen exposure, such as anovulation, polycystic ovary syndrome and obesity, all considered risk factors for endometrial cancer in young women.4,7,8
Some physicians emphasise the importance of a family history of malignancies, with 10–13 % of first-degree relatives affected with breast, colon, gastric, ovarian or endometrial cancer, or relatives affected with hereditary non-polyposis colorectal cancer (HNPCC).3,8 Previously, we described a higher rate of associated atypical hyperplasia in the young group (12.5 versus 2.4 %) and the histological type was more frequently grade 1 (62.5 versus 43 %) (see Table 1).1,5 The distribution of stages is nearly the same in both age groups, with a similar prevalence of stage I disease in both, although, in stage I, younger patients are more likely to present with disease confined to the uterus (Stage IA).5,9
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- Chiva L, Lapuente F, Corraliza V, et al., Conservative management of patients with early endometrial carcinoma: a systematic review, Clin Transl Oncol, 2008;10:155–62.
- Navarria I, Usel M, Rapiti E, et al., Young patients with endometrial cancer: how many could be eligible for fertility sparing treatment?, Gynecol Oncol, 2009;114:448–51.
- Gallup DG, Stock RJ, Adenocarcinoma of the endometrium in women 40 years of age or younger, Obstet Gynecol, 1984;64:417–20.
- Soliman PT, Oh JC, Schmeler KM, et al., Risk factors for young premenopausal women with endometrial cancer, Obstet Gynecol, 2005;105:575–80.
- Evans-Metcalf ER, Brooks SE, Reale FR, Baker SP, Profile of women 45 years of age and younger with endometrial cancer, Obstet Gynecol, 1998;91:349–54.
- Takeshima N, Hirai Y, Yano K, et al., Ovarian metastasis in endometrial carcinoma, Gynecol Oncol, 1998;70:183–7.
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- Morrow CP, Bundy BN, Kurman RJ, et al., Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of endometrium: a Gynecologic Oncology Group study, Gynecol Oncol, 1991;40:55–65.
- Minaguchi T, Nakagawa S, Takazawa Y, et al., eCombined phospho-Akt and PTEN expressions associated with post-treatment hysterectomy after conservative progestin therapy in complex atypical hyperplasia and stage Ia, G1 adenocarcinoma of the endometrium, Cancer Lett, 2007;248:112–22.
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- Horowitz NS, Dehdashti F, Herzog TJ, et al., Prospective evaluation of FDG-PET for detecting pelvic and para-aortic lymph node metastasis in uterine corpus cancer, Gynecol Oncol, 2004;95:546–51.
- Morice P, Fourchotte V, Sideris L, et al., A need for laparoscopic evaluation of patients with endometrial carcinoma selected for conservative treatment, Gynecol Oncol, 2005;96:245–8.
- Saegusa M, Okayasu I, Progesterone therapy for endometrial carcinoma reduces cell proliferation but does not alter apoptosis, Cancer, 1998;83:111–21.
- Chiva L, Lapuente F, Cortijo LG, et al., Sparing fertility in young patients with endometrial cancer, Gynecol Oncol, 2008;111:101–4.
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- Minig L, Franchi D, Boveri S, et al., Progestin intrauterine device and GnRH analogue for uterus-sparing treatment of endometrial precancers and well-differentiated early endometrial carcinoma in young women, Ann Oncol, 2011;22(3):643–9.
- Ramirez PT, Frumovitz M, Bodurka DC, et al., Hormonal therapy for the management of grade 1 endometrial adenocarcinoma: a literature review, Gynecol Oncol, 2004;95:133–8.
- Yasuda M, Matsui N, Kajiwara H, et al., Malignant transformation of atypical endometrial hyperplasia after progesterone therapy showing germ-cell tumor-like differentiation, Pathol Int, 2004;54:451–6.
- Ota T, Yoshida M, Kimura M, Kinoshita K, Clinicopathologic study of uterine endometrial carcinoma in young women aged 40 years and younger, Int J Gynecol Cancer, 2005;15:657–62.
- Ferrandina G, Zannoni GF, Gallotta V, et al., Progression of conservatively treated endometrial carcinoma after full term pregnancy: a case report, Gynecol Oncol, 2005;99:215–7.
- Rubatt JM, Slomovitz BM, Burke TM, Broaddus RR, Development of metastatic endometrial endometrioid adenocarcinoma while on progestin therapy for endometrial hyperplasia, Gynecol Oncol, 2005;99:472–6.
- . Ushijima K, Yahata H, Yoshikawa H, 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;25:2798–803.
- Cormio G, Martino R, Loizzi V, et al., A rare case of choroidal metastasis presented after conservative management of endometrial cancer, Int J Gynecol Cancer, 2006;16:2044–8.
Keywords: Endometrial carcinoma, conservative treatment, fertility sparing, young patients