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Endometrial Cancer
GMJ News knowledge hub · last reviewed August 2026 · Georgian Medical Journal
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Endometrial (uterine) cancer — with 417,367 new cases and 97,370 deaths in 2020 — is the most common gynaecological cancer in high-income countries, with incidence rising globally as obesity rates climb: obesity increases endometrial cancer risk by approximately 6-fold, through chronic unopposed oestrogen exposure from adipose tissue (IARC GLOBOCAN 2020). The TCGA molecular classification has transformed endometrial cancer management — identifying four prognostic subgroups (POLE-ultramutated, mismatch repair-deficient/MSI-high, copy number-low and TP53-mutated) that guide treatment. Pembrolizumab + lenvatinib and dostarlimab for mismatch repair-deficient endometrial cancer have transformed outcomes in advanced disease.
Key messages
417K cases — obesity-driven epidemic
Endometrial cancer caused 417,367 new cases and 97,370 deaths in 2020 — the most common gynaecological cancer in high-income countries. Rising global incidence is directly linked to the obesity epidemic, as adipose tissue converts androgens to oestrogen, causing chronic unopposed oestrogen stimulation (IARC GLOBOCAN 2020).
6-fold risk from obesity
Obesity increases endometrial cancer risk approximately 6-fold — the strongest modifiable risk factor. Every 5-unit increase in BMI is associated with approximately 50-60% increased risk. Other key risk factors: unopposed oestrogen exposure (anovulation, polycystic ovary syndrome, tamoxifen use, late menopause, nulliparity); type 2 diabetes; Lynch syndrome.
Molecular classification transforms treatment
The TCGA molecular classification (2013) identifies four endometrial cancer subgroups: POLE-ultramutated (best prognosis — approximately 10%); mismatch repair-deficient/MSI-high (approximately 25% — responds to immunotherapy); copy number-low/no specific molecular profile (approximately 39%); TP53-mutated (worst prognosis — approximately 26%).
Pembrolizumab and dostarlimab — immunotherapy breakthrough
Pembrolizumab + lenvatinib (KEYNOTE-146/775 trials) and dostarlimab + carboplatin/paclitaxel (RUBY trial) have significantly improved progression-free and overall survival in advanced/recurrent endometrial cancer — particularly in mismatch repair-deficient (dMMR/MSI-high) tumours.
75% diagnosed at stage I — very curable
Approximately 75% of endometrial cancers are diagnosed at stage I (confined to the uterus) — with 5-year survival exceeding 90%. Most patients present early due to postmenopausal bleeding, which should always be investigated urgently.
Prevention through weight management
Endometrial cancer is substantially preventable: weight loss, physical activity, and combined oral contraceptive pill use all reduce risk. Progestogen use opposes oestrogen-driven endometrial proliferation — sequential HRT is safer than oestrogen-only.
Key statistics
Endometrial cancer incidence trend by region — rising with obesity (GLOBOCAN)
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Cervical cancerOvarian cancerObesityPCOSCancerLynch syndrome (NHC risk)
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