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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.
p53-abnormal endometrial cancer is the aggressive class, dominated by serous carcinoma, whose cells have lost the p53 guardian gene and carry scrambled chromosomes. It is the one group that clearly gains from adding chemotherapy to radiotherapy after surgery, and about a quarter of serous tumours overexpress HER2, which trastuzumab and trastuzumab deruxtecan can target.
Abnormal p53 immunohistochemistry, either strong diffuse nuclear staining or complete absence, marks a TP53 mutation and defines the copy-number-high class of the TCGA. Uterine serous carcinoma is its archetype: a tumour of older, often thinner women that arises from atrophic endometrium through serous endometrial intraepithelial carcinoma, spreads through the peritoneum like ovarian cancer and is p53-abnormal in almost every case. Carcinosarcoma, clear cell carcinoma and a fifth of grade 3 endometrioid tumours also fall into the class. HER2 is amplified or overexpressed in about a quarter to a third of serous carcinomas, PIK3CA and PPP2R1A mutations are common, and there are no POLE or mismatch-repair defects. Even stage IA disease confined to a polyp can recur at a distance, so full staging with omental sampling is standard.
PORTEC-3 randomised women with high-risk endometrial cancer to pelvic radiotherapy alone or chemoradiation followed by four cycles of carboplatin-paclitaxel; overall survival at five years was 81.4 percent against 76.1 percent, with a hazard ratio of 0.70, and the molecular analysis showed the benefit was concentrated in p53-abnormal tumours, which had the worst outcome of the four classes and the largest absolute gain from chemotherapy. The ESGO/ESTRO/ESP guideline therefore recommends chemotherapy with or without radiotherapy for p53-abnormal disease from stage I with myometrial invasion onwards. For HER2-positive serous carcinoma a randomised phase 2 trial added trastuzumab to carboplatin-paclitaxel and improved progression-free and overall survival, which the NCCN adopted for advanced and recurrent disease. In DESTINY-PanTumor02 trastuzumab deruxtecan produced responses in 57.5 percent of HER2-expressing endometrial cancers and 84.6 percent of those with 3+ staining, earning a tumour-agnostic approval for HER2 3+ tumours in 2024.
| Setting | Approach | Guideline |
|---|---|---|
| Surgery and staging | Hysterectomy with bilateral salpingo-oophorectomy, sentinel node mapping and omental sampling, with peritoneal assessment because serous tumours spread like ovarian cancer. | not mapped |
| Adjuvant, stage I to III | Carboplatin-paclitaxel chemotherapy, with pelvic radiotherapy and vaginal brachytherapy as in PORTEC-3; chemotherapy is recommended for all p53-abnormal tumours with myometrial invasion. | not mapped |
| Advanced or recurrent HER2-positive serous | Trastuzumab added to carboplatin-paclitaxel and continued as maintenance; trastuzumab deruxtecan for HER2-expressing disease after chemotherapy (DESTINY-PanTumor02). | not mapped |
| Advanced or recurrent HER2-negative | Carboplatin-paclitaxel with dostarlimab or pembrolizumab as for other endometrial cancers, though the immunotherapy gain is smaller in mismatch-repair-proficient disease; lenvatinib-pembrolizumab after platinum. | not mapped |