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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Endometrial cancer with no specific molecular profile is the default class: no POLE mutation, intact mismatch repair and normal p53. Most are low-grade, oestrogen-driven tumours cured by hysterectomy, and hormone-blocking drugs are their most natural treatment when they do recur.
The class is defined by exclusion: POLE wild-type, mismatch-repair proficient and p53 wild-type. It corresponds to the copy-number-low class of the TCGA and holds about half of endometrial cancers, dominated by grade 1 and 2 endometrioid carcinoma with PTEN, PIK3CA, ARID1A and CTNNB1 mutations and strong oestrogen and progesterone receptor expression. Outcome depends on the classical factors, grade, depth of invasion, lymphovascular space invasion and stage, and two markers refine risk within the class: L1CAM expression and loss of oestrogen receptor mark a worse group, and CTNNB1 mutation raises recurrence risk in otherwise low-risk tumours. The WHO 2020 classification and the ESGO/ESTRO/ESP guideline place low-grade, receptor-positive disease in the favourable group and high-grade or receptor-negative disease closer to p53-abnormal risk.
Treatment follows stage and risk. Stage IA grade 1 to 2 disease without lymphovascular invasion is cured by hysterectomy alone; intermediate risk receives vaginal brachytherapy after PORTEC-2 showed it equivalent to pelvic radiotherapy for vaginal control; high-intermediate risk receives pelvic radiotherapy. PORTEC-3 found no meaningful benefit from adding chemotherapy in this class, and RAINBO's NSMP-ORANGE trial is testing whether adjuvant progestin therapy can replace chemotherapy for receptor-positive stage II to III disease. Young women with grade 1 tumours confined to the endometrium can be treated with a levonorgestrel intrauterine device or oral progestins to preserve fertility, with hysterectomy once childbearing is complete.
| Setting | Approach | Guideline |
|---|---|---|
| Low risk (stage IA grade 1 to 2, no substantial LVSI) | Hysterectomy with bilateral salpingo-oophorectomy and sentinel node mapping; no adjuvant treatment. | not mapped |
| Intermediate and high-intermediate risk | Vaginal brachytherapy (PORTEC-2) or pelvic radiotherapy; chemotherapy adds little in this class. | not mapped |
| Fertility-sparing (grade 1, stage IA, no invasion) | Levonorgestrel intrauterine device or oral progestin with hysteroscopic sampling every three to six months; hysterectomy after childbearing. | not mapped |
| Advanced or recurrent, first line | Carboplatin-paclitaxel with pembrolizumab or dostarlimab (smaller benefit than in dMMR); endocrine therapy for low-grade receptor-positive disease. | not mapped |
| After platinum | Lenvatinib with pembrolizumab (KEYNOTE-775); aromatase inhibitor with or without a CDK4/6 inhibitor in receptor-positive disease. | not mapped |