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

Abstract

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.

Adolescent and Young Adult Oncology, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology

“…142 However, caution is needed in endometrial cancer, where progestin therapy has been associated with high rates of cancer recurrence. 143 This may be prevented by combining metformin with medroxyprogesterone.…”

Conservative Management of Endometrial Cancer

“…Progestin is the synthetic analog (generally administered by pill form) to the naturally synthesized progesterone in the body. The mechanism of action of progestins is downregulation of estrogen receptors, activation of enzymes involved in estrogen metabolism, and cell cycle regulation of cyclin-dependent kinase pathways (Park and Nam 2015). Oral progesterone-based agents are the most widely studied therapy for conservative management, and the most commonly used agents include medroxyprogesterone acetate (MPA) and megestrol acetate (MA).…”

“…Additionally, inhibitors of phosphatidylinositol 3-kinase (PI3K), NDA-dependent protein kinase, and VEGF inhibitors (i.e., bevacizumab, aflibercept), and metformin are being investigated (Dedes et al 2011;Park and Nam 2015). However, trials to date have been largely performed in women with recurrent or advanced EC, and these agents have not been investigated in frontline treatment for fertility-sparing therapy for EC except for a couple case reports.…”

Aromatase inhibitors of the third generation in endocrine therapy of breast cancer and endometrial cancer: the successes and failures of the combination therapy

“…Например, в исследовании K.S. [43]. В проспективном клиническом исследовании (n = 35) больные рецидивирующим РЭ, имею-щие в анамнезе до начала исследования не менее двух линий химиотерапии, получали комбиниро-ванную пероральную терапию: эверолимус (10 мг) и летрозол (2,5 мг в сутки) с продолжительностью каждого цикла лечения 4 недели.…”