Elsevier

The Lancet

Volume 366, Issue 9484, 6–12 August 2005, Pages 491-505
The Lancet

Seminar
Endometrial cancer

https://doi.org/10.1016/S0140-6736(05)67063-8Get rights and content

Summary

Each year, endometrial cancer develops in about 142 000 women worldwide, and an estimated 42 000 women die from this cancer. The typical age-incidence curve for endometrial cancer shows that most cases are diagnosed after the menopause, with the highest incidence around the seventh decade of life. The appearance of symptoms early in the course explains why most women with endometrial cancer have early-stage disease at presentation. For all stages taken together, the overall 5-year survival is around 80%. There is a substantial prognostic difference between the histological types of endometrial cancers. The most common lesions (type 1) are typically hormone sensitive and low stage and have an excellent prognosis, whereas tumours of type 2 are high grade with a tendency to recur, even in early stage. The cornerstone of treatment for endometrial cancer is surgery, which not only is important for staging purposes but also enables appropriate tailoring of adjuvant treatment modalities that benefit high-risk patients only. We review current concepts about epidemiology, pathology, pathogenesis, risk factors and prevention, diagnosis, staging, prognostic factors, treatment, and follow-up of endometrial cancer.

Section snippets

Pathology

Pathological examination is the cornerstone of diagnosis of endometrial cancer (figure 1). About 80% of all endometrial carcinomas are of the endometrioid type (figure 2); this term refers to endometrial-type glands of varying differentiation easily recognisable on microscopy.10 Several subtypes or variants of endometrioid carcinoma have been described, such as secretory carcinoma and villoglandular carcinoma (panel 1). The former resembles a secretory endometrium, because glycogen vacuoles are

Pathogenesis

The endometrium undergoes structural modification and changes in specialised cells in response to fluctuations of oestrogen and progesterone during the menstrual cycle. Long-lasting unopposed oestrogen exposure leads to endometrial hyperplasia, which increases the chance of development of atypical hyperplasia and eventually type-1 endometrial cancer. The molecular basis of this process is still not known, since the involvement of only a minority of factors is reproducible.10 Endometrial

Risk factors and primary prevention

Women with type-1 endometrial cancer are likely to have been exposed to unopposed oestrogens (panel 2). Oestrogen-producing tumours are an uncommon risk factor. Unopposed oestrogens should no longer be used to treat postmenopausal symptoms in women who have not had hysterectomy. Excessive fat consumption and overweight (defined as body-mass index [BMI] of at least 25 kg/m2) are important risk factors present in almost 50% of women with endometrial cancer.45, 46, 47, 48, 49, 50 In premenopausal

Secondary prevention

There is no point in screening for endometrial cancer; screening is unlikely to decrease mortality from the disorder. It will mainly detect women with low-risk tumours.100 Furthermore, minimally invasive modalities potentially suitable for mass screening, including transvaginal ultrasonography (TVU) and cytology from a Pap smear or endometrial brush, have limited accuracy for the diagnosis of endometrial cancer in an asymptomatic population.101, 102 Education about the importance of

Symptoms and diagnosis

Abnormal uterine bleeding is the most frequent symptom of endometrial cancer, but many other disorders give rise to the same symptom. All postmenopausal women with vaginal bleeding and those with abnormal uterine bleeding associated with risk factors for endometrial cancer or hyperplasia (eg, polycystic ovaries, obesity, age over 40 years, erratic cycles, hormone-replacement therapy, tamoxifen use) should undergo further diagnostic endometrial assessment. The probability of endometrial cancer

Staging

Endometrial cancer is a surgically staged disease, because clinical estimates and preoperative imaging of the extent are incorrect in over 20% of cases.13 The depth of myometrial invasion and extrauterine disease (uterine serosa, adnexal involvement, peritoneal cytology, intra-abdominal, and lymph nodes) have all been incorporated into the FIGO staging scheme (table). Although the preoperative assessment of extent cannot replace FIGO staging, and it does not lead to better survival, it enables

Prognostic factors and survival

The most important prognostic features in endometrial cancer are the surgical FIGO stage, myometrial invasion, histological type, and differentiation grade; most are independent of each other (panel 3).131, 132, 133, 134, 135 Whether the 5–15% of patients with positive peritoneal cytology in the absence of extrauterine disease also classified as having stage IIIA lesions have a different outcome from those with negative cytology remains controversial.136, 137 Apart from this uncertainty, the

Surgery

The most important therapy for endometrial cancer is surgery. The procedures include acquisition of peritoneal fluid or washings for cytology, total hysterectomy including the uterine cervix, and bilateral salpingo-oophorectomy; in selected cases, there is a place for omentectomy and a thorough retroperitoneal lymph-node dissection.

Although the results of randomised trials are still lacking, in experienced hands, laparoscopy-assisted vaginal hysterectomy is feasible when operating for

Follow-up

Weight loss, pain, and vaginal bleeding can suggest recurrent disease, which mostly occurs during the first 3 years after primary treatment. Although follow-up visits are organised in most settings, retrospective data suggest that there is no difference in survival between symptomatic and asymptomatic recurrences, or between women with recurrences detected during routine follow-up visits and those with recurrences detected during the interval between routine visits.199 Furthermore, follow-up of

Search strategy and selection criteria

We searched PubMed with the term “endometrial cancer” in combination with the terms “epidemiology”, “pathology”, “pathogenesis”, “risk factors”, “prevention”, “diagnosis”, “staging”, “prognostic factors”, “tamoxifen”, “surgery”, “radiotherapy”, “hormonotherapy”, and “chemotherapy”. We mainly included results from randomised trials undertaken by large groups such as the Gynaecological Oncology Group and the European Organisation for Research and Treatment of Cancer. We also refer to

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