Progestin intrauterine device and GnRH analogue for uterus-sparing treatment of endometrial precancers and well-differentiated early endometrial carcinoma in young women

Minig, Lucas; Franchi, D.; Boveri, Sara; Casadio, Chiara; Bocciolone, Luca; Sideri, Mario

doi:10.1093/annonc/mdq463

Cited by 123 publications

(78 citation statements)

References 27 publications

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“…Recently, a slightly lower CR rate was obtained by using LNG-IUD in combination with a GnRH analogue (gonadotropin-releasing hormone) in 14 patients [6]. Additional methods such as tumor resection guided by hysteroscopy and followed by LNG-IUD insertion [11] or by oral progestins [7] resulted in CR in all of the 14 patients studied [7,11].…”

Section: Patient Selection and Conservative Treatmentmentioning

confidence: 99%

“…Using this strategy, complete response (CR) was reported in over 60-70% [4,5]. In addition, many of these women were able to achieve full-term pregnancies [6]. Recently, other strategies such as the local administration of hormone therapy through the insertion of a levonorgestrel-intrauterine device (LNG-IUD) [6] or tumor resection guided by hysteroscopy have also been studied [7].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, many of these women were able to achieve full-term pregnancies [6]. Recently, other strategies such as the local administration of hormone therapy through the insertion of a levonorgestrel-intrauterine device (LNG-IUD) [6] or tumor resection guided by hysteroscopy have also been studied [7]. Nonetheless, the results of these fertility-preserving treatments in early EC are determined by several factors such as patient selection, variability in interobserver histologic diagnosis, variable type, dosage, type and duration of hormonal treatment, and type of evaluation before treatment and surveillance after treatment.…”

Section: Introductionmentioning

confidence: 99%

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Controversies of the Hormonal Conservative Treatment of Endometrial Cancer

Minig

Franchi

Bernabe

et al. 2013

Gynecol Obstet Invest

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Background: Hysterectomy plus salpingo-oophorectomy represents the standard treatment for patients with well-differentiated endometrial cancer (EC) limited to the endometrium. It is estimated that over 5% of EC are diagnosed in nulliparous women aged 35-44 years. In addition, EC can affect obese women with diabetes, hypertension and other comorbidities increasing the surgical risk. Methods: This article reviews the English literature in PubMed regarding hormonal treatment of EC. Results: Use of hormonal therapies has resulted in complete remission in 60-70%; many of these women were able to achieve full-term pregnancies, and in case of contraindication to surgery, resection could be avoided. Several topics, however, such as patient selection, interobserver histologic evaluation, the type/duration of hormonal treatment, modality of evaluation before treatment and surveillance after treatment, which are still subject to controversy, are therefore discussed in this paper. Conclusion: Uterus-sparing treatment of well-differentiated EC limited to the endometrium is feasible and has acceptable efficacy in women with increased surgical risk or those who wish to preserve their fertility. Although the methods applied to determine disease extent beyond the endometrium are still unsatisfactory, patient selection is a crucial factor determining the outcome of treatment. However, women must be fully informed about the possibility of treatment failure and the necessity of a close follow-up after therapy.

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Section: Patient Selection and Conservative Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Controversies of the Hormonal Conservative Treatment of Endometrial Cancer

Minig

Franchi

Bernabe

et al. 2013

Gynecol Obstet Invest

View full text Add to dashboard Cite

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“…Current fertility-sparing treatment modalities mainly comprise hormonal therapies involving progestins [12][13][14][15][16], progestin-releasing intrauterine devices [17][18][19][20][21], natural progesterone [22], oral contraceptives [23], selective estrogen receptor modulators [24][25][26],gonadotropin-releasing hormone agonist [24,27], and aromatase inhibitors [28]. Of these treatments, progestin therapy is the most commonly used, and its efficacy is well-known compared with other treatment modalities.…”

Section: Introductionmentioning

confidence: 99%

Progestins in the Fertility-Sparing Treatment and Retreatment of Patients With Primary and Recurrent Endometrial Cancer

Nam

2015

The Oncologist

109

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Endometrial cancer is the most common gynecologic cancer in developed countries. Approximately 3%-14% of endometrial cancers are diagnosed in young women under 40 who want to preserve their fertility. The incidence of endometrial cancer in this age group is increasing, for which fertility-sparing therapy is increasingly used because it is one of the most important quality of life issues in these women. Progestin therapy is the most common type of fertility-sparing therapy. In this review, the most up-to-date findings regarding fertility-sparing progestin therapy for young women with primary and recurrent endometrial cancer is addressed in terms of diagnosis, treatment, follow-up, and oncologic and reproductive outcomes. Fertility-sparing progestin therapy is highly effective in selected young women with primary and recurrent endometrial cancer. The selection of appropriate patients through comprehensive pretreatment evaluation is of paramount importance to achieve the best outcomes without compromising survival. Because of the high rate of recurrence after successful fertility-sparing therapy, close surveillance is mandatory, and prophylactic hysterectomy is the best option for patients who have completed family planning. Pregnancy outcomes are very promising with the aid of assisted reproductive technologies. Continuous daily oral medroxyprogesterone acetate and megestrol acetate are the preferred progestins for fertility-sparing therapy, but future studies should be performed to determine the optimal dose and treatment duration of these agents. The Oncologist 2015; 20:270-278 Implications for Practice: In young women with endometrial cancer, the cure rate is very high.Therefore, the efficacy of treatment should not be limited to the oncologic outcomes.The quality-of-life issue is as important as oncologic outcomes in these patients. Fertility preservation is one of the most important quality-of-life issues. Based on the results of numerous studies, fertility-sparing progestin therapy can be safely performed in endometrioid adenocarcinoma confined to the endometrium. It also can be reasonably recommended to selected women with more advanced disease and recurrent disease. However, careful follow-up is important because of the high rate of recurrence.

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“…9,10 More recently, local delivery by progestinimpregnated intrauterine device has also shown to be effective in some patients, even with successful pregnancies thereafter. 11 Glands with molecular alterations such as PTEN inactivation appear to be particularly sensitive to exogenous progestins, as PTEN-null glands preferentially disappear after treatment in most cases. 12 In cases of EIN with a secretory background at presentation, the presence of endogenous circulating progesterone may have an antiproliferative effect in neoplastic glands, similar to that seen with exogenous progestin therapies.…”

Section: Discussionmentioning

confidence: 99%

Endometrial intraepithelial neoplasia with secretory differentiation: diagnostic features and underlying mechanisms

2013

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Endometrial intraepithelial neoplasia (EIN) with secretory differentiation and ordinary EIN occurring in a secretory context are rare but recognized findings. We determined how often secretory differentiation in EIN was associated with evidence of circulating progestins in the background endometrium, and studied clinical characteristics and clinical outcomes of affected patients. We selected 41 patients with secretory differentiation in either the EIN itself (n ¼ 31) and/or background endometrium (n ¼ 38). Most (90%, 28/31) secretory EINs were associated with circulating progestins. Rare exceptions were observed, suggesting that secretory EIN may occur as a hormone-independent phenomenon. Circulating progestins are not sufficient, however, to induce EIN secretory differentiation, as 26% (10/38) of EIN within a secretory background were of the ordinary (nonsecretory) type. EIN patients with secretory endometrium in the background are younger (averaging 45 years) than the aggregate group of all patients with EIN (53 years in previously published studies) and are often premenopausal with a cyclical source of endogenous progestins. Involution of EIN during follow-up was more frequent (81%, 17/21) for those with a secretory background at the time of initial EIN diagnosis compared with historical averages (25%, 36/142). These results suggest a potential role for endogenous progesterone, as well as therapeutic progestins, in modulating EIN outcomes. Modern Pathology (2013) 26, 868-873; doi:10.1038/modpathol.2012.231; published online 18 January 2013 Keywords: endometrial cancer; endometrial intraepithelial neoplasia; secretory Endometrial intraepithelial neoplasia (EIN) is a clonal proliferation of endometrial glands, considered to be a premalignant condition due to its strong association with concurrent and/or subsequent endometrioid (type I) adenocarcinoma of the endometrium. Indeed, a diagnosis of EIN is associated with a 27% likelihood of having ('concurrent') adenocarcinoma within 1 year, and carrying a 45-fold increased risk for a future (after 1 year) diagnosis of adenocarcinoma. 1 Diagnosis of EIN requires strict application of histological criteria, including size (at least 1 mm in greatest linear dimension), architecture (area of glands exceeds area of endometrial stroma) and cytology (difference in nuclear and cytoplasmic appearance between the abnormal and background endometrium). [2][3][4] Exclusion of cancer, as well as benign conditions mimicking EIN, is an important part of accurate diagnosis.Accurate and sensitive diagnosis of EIN in reproductive age women can be challenging when a secretory background is present. Secretory-phase endometrium displays changes that may morphologically overlap with EIN. 2 In normal mid-late secretory endometrium the gland to stroma ratio is increased, nuclei become enlarged and round, and large expanses of secretory superficial endometrium are offset from basal areas lacking secretory changes. Furthermore, when EIN does occur within the context of a secretory environment,...

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Progestin intrauterine device and GnRH analogue for uterus-sparing treatment of endometrial precancers and well-differentiated early endometrial carcinoma in young women

Abstract: The combined treatment showed effectiveness in a substantial proportion of patients with AEH and EC. Close follow-up during and after treatment is crucial.

Cited by 123 publications

References 27 publications

Controversies of the Hormonal Conservative Treatment of Endometrial Cancer

Controversies of the Hormonal Conservative Treatment of Endometrial Cancer

Progestins in the Fertility-Sparing Treatment and Retreatment of Patients With Primary and Recurrent Endometrial Cancer

Endometrial intraepithelial neoplasia with secretory differentiation: diagnostic features and underlying mechanisms

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