Fertility-Sparing Approaches in Atypical Endometrial Hyperplasia and Endometrial Cancer Patients: Current Evidence and Future Directions

Abstract

Endometrial cancer (EC) is the fourth most common cancer in women in developed countries. Although it is usually diagnosed in postmenopausal women, its incidence has increased in young women, as well in recent decades, with an estimated rate of 4% in those under 40 years of age. Factors involved in this increase, particularly in resource-rich countries, include delayed childbearing and the rise in obesity. The new molecular classification of EC should help to personalize treatment, through appropriate candidate selection. With the currently available evidence, the use of oral progestin either alone or in combination with other drugs such as metformin, levonorgestrel-releasing intrauterine devices and hysteroscopic resection, seems to be feasible and safe in women with early-stage EC limited to the endometrium. However, there is a lack of high-quality evidence of the efficacy and safety of conservative management in EC. Randomized clinical trials in younger women and obese patients are currently underway.

The role of bariatric and metabolic surgery in the development, diagnosis, and treatment of endometrial cancer

“…Thus, women with obesity are less likely to undergo minimally invasive approaches and are at a much higher risk for developing postoperative complications (e.g., wound infection, venous thromboses, and prolonged length of stay ( 81 )). As obesity rates continue to rise and childbearing is increasingly deferred, growing numbers of endometrial cancer may be found in women desiring uterine preservation and progestin based therapies may be appropriate ( 82 ). Bariatric surgery is effective in achieving weight loss, restoring the hypothalamic–pituitary axis which is deranged in many of these women, and optimizing pregnancy outcomes ( 83 ).…”

Conservative Management of Atypical Endometrial Hyperplasia and Early Endometrial Cancer in Childbearing Age Women

“…Lynch syndrome is an inherited condition predisposing to colorectal cancer, EC, gastric cancer, and other malignancies, and accounts for 2 to 5% of all endometrial malig-nancies [29][30][31]. This autosomal dominant hereditary syndrome with high penetrance is caused by the mutation of a mismatch repair gene that is involved in DNA mismatch repair (MMR)/microsatellite instability (MSI): MLH1, MSH 2 or 6, and PMS2 [6]. It affects 1 out of 370 to 2000 persons in Western countries [32,33].…”

“…In 2013, the Cancer Genome Atlas Research Network published a molecular diagnostic classification that defines four prognostic categories in endometrial cancer: POLE ultramutated, microsatellite instability hypermutated, low copy-number tumor, and high copynumber tumor [6,23,37].…”

“…Hence, they are used for the risk stratification of patients. Some mutations are already well-known and considered in the clinical setting for the management of patients; however, they have not yet been included in the decision algorithm for fertility-sparing treatment [6,38]. A recent review [38] identifies and summarizes the currently established genetic prognostic factors included in the prognostic categories, aiming to establish whether they facilitate the decision for fertility sparing in early endometrial cancer.…”

“…Although EC usually occurs after menopause, up to 14% of diagnoses are in premenopausal women [3], with over 5% of cancers diagnosed between 35 and 44 years, and 2% between 20 and 24 years [4]. Several risk factors are linked to the development of endometrial cancer, among them: high BMI or obesity, hyperinsulinemia, diabetes, hypertension, nulliparity, and anovulatory cycles [5,6].…”