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      Comparison of fertility-sparing treatments in patients with early endometrial cancer and atypical complex hyperplasia : A meta-analysis and systematic review

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          Abstract

          Background:

          There are some fertility-sparing treatments in patients with early endometrial cancer (EEC) or atypical complex hyperplasia (ACH), and the objective is to compare them by evaluating the oncologic and reproductive outcomes.

          Methods:

          We searched the published literature using Medline, Cochrane, EMBASE, and Google Scholar databases up to January 3, 2017, with various combinations of keywords fertility-sparing treatments, progesterone, progestin, intrauterine devices, early endometrial cancer, and atypical complex hyperplasia. The primary endpoint is the complete response (CR) rate, and the secondary endpoints are the partial response (PR) rate, relapse rate (RR), pregnancy rate, and live birth rate.

          Results:

          Twenty-eight studies containing 1038 women with EEC or ACH were included for review and meta-analysis. The results demonstrated that women with EEC or ACH managed with progestin had a pooled CR rate of 71% (95% confidence interval [CI]: 63–77%). The pooled pregnancy outcomes showed that 34% of women taking progestin treatment for EEC or ACH became pregnant (95% CI: 30–38%); however, only 20% of them delivered live newborns. The pooled CR rate for women using intrauterine device (IUD) was 76% (95% CI: 67–83%), and pooled RR was 9% (95% CI: 5–17%). The pregnancy rate for women whom underwent IUD was 18% (95% CI: 7–37%), and 14% of them delivered live newborns. In patients using progestin plus IUD, the pooled CR rate was 87% (95% CI: 75–93%); among those patients, 40% became pregnant (95% CI: 20–63%), and 35% delivered live newborns. There is no publication bias for the CR rate.

          Conclusion:

          For patients with EEC and ACH, treatments with progestin, with or without IUD, or IUD alone can reach good CR rate; however, the pregnancy outcomes might be worse in patients treated with IUD alone. Further randomized-controlled studies are warranted to find out a better solution.

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          Most cited references43

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          Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review.

          Camille C Gunderson, Amanda Fader, Kathryn Carson … (2012)
          The objective of this review was to analyze published contemporary oncologic and reproductive outcomes in women with endometrial hyperplasia or cancer undergoing medical management with progestin therapy. A systematic review of oncologic and pregnancy outcomes in women with complex atypical hyperplasia or grade 1 adenocarcinoma was performed using a comprehensive search of the MEDLINE literature. English language studies published from 2004 to 2011 which utilized hormonal therapy were identified using key words endometrial hyperplasia, endometrial cancer, fertility preservation, hormone and progestin therapy. Fisher's exact test was used to calculate statistical differences. Forty-five studies with 391 study subjects were identified. The median age was 31.7 years. Therapies included medroxyprogesterone (49%), megestrol acetate (25%), levonorgestrel intrauterine device (19%), hydroxyprogesterone caproate (0.8%), and unspecified/miscellaneous progestins (13.5%). Overall, 344 women (77.7%) demonstrated a response to hormonal therapy. After a median follow up period of 39 months, a durable complete response was noted in 53.2%. The complete response rate was significantly higher for those with hyperplasia than for women with carcinoma (65.8% vs. 48.2%, p=.002). The median time to complete response was 6 months (range, 1-18 months). Recurrence after an initial response was noted in 23.2% with hyperplasia and 35.4% with carcinoma during the study periods (p=.03). Persistent disease was observed in 14.4% of women with hyperplasia and 25.4% of women with carcinoma (p=.02). During the respective study periods, 41.2% of those with hyperplasia and 34.8% with a history of carcinoma became pregnant (p=.39), with 117 live births reported. Based on this systematic review of the contemporary literature, endometrial hyperplasia has a significantly higher likelihood of response (66%) to hormonal therapy than grade 1 endometrial carcinoma (48%). Disease persistence is more common in women with carcinoma (25%) compared to hyperplasia (14%). Reproductive outcomes do not seem to differ between the cohorts. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis.

            Ioannis D Gallos, Jason Yap, Madhurima Rajkhowa … (2012)
            The objective of the study was to evaluate the regression, relapse, and live birth rates of early-stage endometrial cancer (EC) and atypical complex hyperplasia (ACH) with fertility-sparing treatment.
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              Multicenter phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women.

              M Hiura, Toshiharu Kamura, Masaharu Fukunaga … (2007)
              To assess the efficacy of fertility-sparing treatment using medroxyprogesterone acetate (MPA) for endometrial carcinoma (EC) and atypical endometrial hyperplasia (AH) in young women. This multicenter prospective study was carried out at 16 institutions in Japan. Twenty-eight patients having EC at presumed stage IA and 17 patients with AH at younger than 40 years of age were enrolled. All patients were given a daily oral dose of 600 mg of MPA with low-dose aspirin. This treatment continued for 26 weeks, as long as the patients responded. Histologic change of endometrial tissue was assessed at 8 and 16 weeks of treatment. Either estrogen-progestin therapy or fertility treatment was provided for the responders after MPA therapy. The primary end point was a pathologic complete response (CR) rate. Toxicity, pregnancy rate, and progression-free interval were secondary end points. CR was found in 55% of EC cases and 82% of AH cases. The overall CR rate was 67%. Neither therapeutic death nor irreversible toxicities were observed; however, two patients had grade 3 body weight gain, and one patient had grade 3 liver dysfunction. During the 3-year follow-up period, 12 pregnancies and seven normal deliveries were achieved after MPA therapy. Fourteen recurrences were found in 30 patients (47%) between 7 and 36 months. The efficacy of fertility-sparing treatment with a high-dose of MPA for EC and AH was proven by this prospective trial. Even in responders, however, close follow-up is required because of the substantial rate of recurrence.
              Article 0 comments Cited 89 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Medicine (Baltimore)
                Journal ID (iso-abbrev): Medicine (Baltimore)
                Journal ID (publisher-id): MEDI
                Title: Medicine
                Publisher: Wolters Kluwer Health
                ISSN (Print): 0025-7974
                ISSN (Electronic): 1536-5964
                Publication date Collection: September 2017
                Publication date (Electronic): 15 September 2017
                Volume: 96
                Issue: 37
                Electronic Location Identifier: e8034
                Affiliations
                [a ]Beijing Obstetrics and Gynecology Hospital, Capital Medical University
                [b ]Department of Obstetrics and Gynecology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.
                Author notes
                [∗ ]Correspondence: Weiyuan Zhang, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Chaoyang District, Beijing, China (e-mail: zhangwy9921@ 123456hotmail.com ); Limin Feng, Department of Obstetrics and Gynecology, Beijing Tian Tan Hospital, Capital Medical University, Dongcheng District, Beijing, China (e-mail: lucyfeng1966@ 123456163.com ).
                Article
                Publisher ID: MD-D-17-02554 Accession ID: 08034
                DOI: 10.1097/MD.0000000000008034
                PMC ID: 5604661
                PubMed ID: 28906392
                SO-VID: 6bc55858-c9bc-4554-9157-c78ac6d9a3c6
                Copyright © Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                Date received : 24 April 2017
                Date revision received : 25 July 2017
                Date accepted : 17 August 2017
                Categories
                Subject: 5600
                Subject: Research Article
                Subject: Systematic Review and Meta-Analysis
                Custom metadata
                OPEN-ACCESS TRUE

                Keywords: atypical complex hyperplasia,early endometrial cancer,fertility-sparing treatments,meta-analysis,systematic review
                Data availability:
                Keywords: atypical complex hyperplasia, early endometrial cancer, fertility-sparing treatments, meta-analysis, systematic review

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