NFOG - Nordic Federation of Societies of Obstetrics and Gynecology

50. Uterine cancers

Take home messages

Endometrial cancer (EC) is the most common gynecological cancer, and the fifth most common cancer among women in the Nordic
countries
Main risk factors are obesity, diabetes and nulliparity
Exclusion of EC is always needed when postmenopausal bleeding occurs
EC has a good prognosis for stage I (confined to the uterus), but it is poor if metastasis occurs
Sarcomas are rare but highly malignant uterine tumors

Introduction to all gynecological cancers

Gynecological cancers are classified according to FIGO (International Federation of Gynecology and Obstetrics, see Table 1), rather than
the traditional TNM-classification. Localized/small tumors (FIGO stage I) have significantly better survival than tumors with distant
spread (Typically FIGO stage IV). Cancers that generally are detected early (such as endometrial cancer after postmenopausal bleeding)
have a mostly good prognosis, while ovarian cancer with few early signs are mostly diagnosed late and thus have a poorer overall
survival rate. The only preventable gynecological cancer (HPV-vaccination, see Chapter Premalignant lesions of the uterine cervix) is also
the only one with a good screening option (cervical smear/HPV-test, described in the Approach to the patient chapter, part Performing
cervical cytology). Following mass vaccination the incidence of cervical cancer will likely decrease in the coming decades. Endometrial
cancer on the other hand has displayed an increased incidence due to the general aging of the population in combination with obesity.

The different cancers and their treatment are described in the specific sub-chapters. The Nordic countries have guidelines that differ
slightly. Links to specific Nordic/European guidelines are displayed in the FIGO table (Table 1).

Table 1, FIGO classification. International Federation of Gynecology and Obstetrics..simplified version. * l.n.= lymph nodes. (click to
enlarge)
Uterine cancer
The majority of uterine cancers originate from the endometrium, the glandular lining of the uterine cavity (Figure 1). EC has been divided
into two different categories: low-risk, Estrogen Receptor (ER) and Progesterone Receptor (PR) positive grade 1-2 endometrioid cancers
with a good prognosis, and the more aggressive high-risk cancers, which are of non-endometrioid histology or poorly differentiated
grade 3 cancers. New molecular genetic classifications are emerging, and EC will likely be more accurately classified to predict prognosis
and the need for adjuvant treatment.

A small proportion (≈5%) of uterine cancers are derived from the muscular uterine wall or connective tissue cells, i.e. sarcomas.

Figure 1. Illustration of Endometrial Cancer. (click to enlarge)

Endometrial cancer

Epidemiology
Endometrial cancer (EC) is the most common gynecological cancer in industrialized countries, comprising nearly 5% of all cancer in
women. The life-time risk for women is nearly 2%. It mostly affects postmenopausal women, with a mean age of 65 years at diagnosis.
The incidence is increasing due to obesity and aging of the population. The age-adjusted incidence rate in all Nordic countries combined
was 13.5/100.000 in 2012-2016, with slight variations between countries (Denmark 13.5, Finland 13.0, Iceland 14.1, Norway 15.5,
Sweden 12.8). The prognosis has improved, from a 5-year disease-specific survival of 75% in 1980 to 87% in 2010.

Diagnosis
An endometrial biopsy should be obtained from all women who present with postmenopausal bleeding, as 10% will have EC. This
probability increases if bleeding is prolonged. A cervical (“PAP”) smear has a low sensitivity to detect EC and will not rule out EC in
women with postmenopausal bleeding as it is designed to detect cervical dysplasia. Women diagnosed with atypical hyperplasia in the
endometrium have a 40% risk of harboring EC.

An endometrial biopsy is usually easily obtained in the out-patient clinic using a small aspirational catheter and a vacuum
aspiration syringe (“Pipelle®”) (see Approach to the patient chapter, Figs 3 &18, video 20). Hysteroscopy and/or fractionated
curettage may be needed (see Minor procedures in Gynecologic surgery chapter).
A vaginal ultrasound examination will increase the sensitivity of detecting a cancer in a polyp. In the ultrasound examination, the
size of the tumor and invasion to the underlying myometrium is estimated.
When EC is diagnosed, a preoperative imaging (CT, MRI or a PET-CT) is used for the detection of possible lymph node or distant
organ metastases. Recommendation of preoperative imaging slightly differs in the Nordic countries: in some countries, patients
with a low-risk endometrioid grade 1-2 cancer do not routinely undergo preoperative imaging.
Treatment
Surgical removal of uterus (hysterectomy) is the mainstay of treatment. Usually the ovaries are removed (bilateral salpingo-
oophorectomy) but may be preserved in selected (low-risk) premenopausal women. In women with a high-risk histology (non-
endometrioid or poorly differentiated endometrioid cancer) or a large or deeply myometrial invading tumor, lymphadenectomy (pelvic
and para-aortal) is recommended for staging purposes. Sentinel node mapping (identifying the “first draining lymph node”) is emerging
as alternative to traditional lymphadenectomy.

Based on the pathological diagnosis of surgical specimen, and imaging results: Patients with grade 1-2 endometrioid cancers with
superficial invasion do not need adjuvant treatment. Patients with non-endometrioid cancers or higher stage cancers are given local or
external radiotherapy, chemotherapy or a combination of these, based on individual risk classification.

With recurrent disease outside the pelvis/lower abdomen, chemotherapy will usually be provided.

The European Society of Gynecologic Oncology guidelines (see Table 1) describe thoroughly treatment recommendations also for
endometrial cancer. There are some differences between the Nordic countries, and national guidelines are followed.

Figure 2. Photo of removed uterus with local endometrial tumor (FIGO stage I).

Figure 3. Photo of large endometrial tumor with extensive spread (bowels) (FIGO stage IV) after radical surgery (click to enlarge).

Prognosis
Most women (80%) are diagnosed with an early stage tumor (FIGO stage I: tumor in uterus, Photo 6, Table 1) in which the 5-year survival
is 95 % percent. Patients with advanced disease (FIGO stage IV: distant metastasis, Photo 7) have a 40% 5-year survival rate (Norwegian
data, while US data report as low as 22%).

From Table 1

Genetics
Most ECs are sporadic (not heritable). Women with Lynch syndrome/HNPCC (defect in mismatch repair leading to risk of cancer
development in colon and endometrium) have a 40-60% lifetime risk of developing EC.

Uterine sarcomas
Epidemiology
Sarcoma is a malignant tumor originating from the muscular layer of uterus, the myometrium. Benign myometrial tumors, myomas, are
very common and are clinically diagnosed in >20% of all women. However, sarcomas are very rare with a yearly incidence of 2/100 000
women. A myoma does not transform in to a sarcoma but approximately 0.5% of women preoperatively presumed to have a myoma will
be identified to have a sarcoma by postoperative histology. It is unknown why a myometrial cell transforms into a sarcoma.

Diagnosis
Gynecological examination may detect an enlarged uterus. Endometrial biopsy may identify endometrial stromal sarcomas but not
leiomyosarcoma. On vaginal ultrasound examination, leiomyosarcomas appear as myomas but can be more heterogeneous in nature and
contain cystic features, irregular borders or atypical circulation. Pelvic MRI is the preferred method for preoperative imaging, but usually
definite diagnosis is obtained only after surgery. Due to risk of spread, biopsies are not recommended.

Treatment
Treatment is hysterectomy by trained gynecological oncologists or sarcoma teams. Radical surgery (free margins) and removal of the
tumor intact (as a whole) are important factors promoting chance of survival. Adjuvant therapy has added little to survival. Radiation has
no proven efficacy. In endometrial stromal sarcomas, hormonal therapies can be used in advanced stages.

Prognosis
The 5-year overall survival is approximately 66%. Large tumor size at diagnosis is associated with poor survival and in patients with
distant metastasis (stage IV), the 5-year overall survival is as low as 29% (2).

Keywords: Endometrial cancer, endometrial stromal sarcoma, leiomyosarcoma, postmenopausal bleeding, atypical hyperplasia

Test yourself
Click at NFOG-MCQ  and then at chapter 50

References

Literature
Murali R, et al. Evolving roles of histologic evaluation and molecular/genomic profiling in the management of endometrial cancer. JNCCN
2018;16(2): 201-9.

Trovik J, et al. Improved survival related to changes in endometrial cancer treatment, a 30-year population based perspective. Gynecol
Oncol. 2012;125(2):381-7.

Colombo N, et al. ESMO -ESGO-ESTRO Consensus Conference on endometrial cancer: diagnosis, treatment. Annals of Oncology
2016;27:16-41.

Kapp DS, Shin JY, Chan JK. Prognostic factors and survival in 1396 patients with uterine leiomyosarcomas: emphasis on impact of
lymphadenectomy and oophorectomy. Cancer 2008;112(4):820-30.

Relevant guidelines regarding gynecological cancer:

ESGO: European Society of Gynecologic Oncology 

NSGO: Nordic Society of Gynecologic Oncology 

National guidelines

DGCG: Dansk Gynekologisk Cancer Gruppe 

Finland:  Finnish 

Iceland:

NFGO: Norsk Forening Gynekologisk Onkologi 

Sweden: Regionala Cancercentrum i Samverkan-Gynekologisk cancer 

Authors
Jone Trovik , MD, professor, Norway.

Annika Auranen , MD, Finland.

Last edited 28.08.2020

Published by:
NFOG - Nordic Federation of Societies of Obstetrics and Gynecology
Ole Mogensen Department of Obstetrics and Gynecology - Aarhus University Hospital
8200 Århus N

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