GENERAL INTRODUCTION 11 1 INTRODUCTION Epidemiology Endometrial cancer (EC) is the most common gynecological malignancy in industrialized countries, like Europe and North America. The incidence is rising due to advanced life expectancy and increasing obesity.1 In 2020 worldwide, 417,367 women were diagnosed with EC and 97,370 people died from this cancer.2 Various risk factors are identified for EC and summarized in Table 1. Low-income countries have a lower incidence of EC, because most risk factors are less present. Within the Netherlands, the reported incidence of EC in 2020 was 2069, with a mortality rate of 559 women, both have increased over the past years.3 The majority of patients diagnosed with EC are between 60-74 years old (50%) and a third of the patients is older than 75 years.3 Table 1. Risk factors for endometrial cancer Increasing factors Long-term exposure to unopposed estrogens Increasing Age Obesity Nulliparity Polycystic ovary syndrome Early menarche/late menopause Hormone replacement therapy without progestogens Others Tamoxifen use for breast cancer Genetic First-degree relative with endometrial cancer Lynch-syndrome Decreasing factors Grand multiparity Increased physical activity Oral conceptive and/or hormone replacement therapy (combination of estrogen & progestogens) Smoking Diagnosis Among EC patients, most women present with abnormal or postmenopausal bleeding as an early symptom.4 The diagnostic work-up consists of gynecological examination including cervical cytology and transvaginal ultrasonography (TVU) to measure endometrial thickness. Thickened endometrium, defined as >4.0 mm, or recurrent abnormal postmenopausal bleeding that occurs six weeks after a first episode within a year, requires histological evaluation by either endometrial sampling, hysteroscopic biopsy or dilatation and
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