Objectives Molecular classification of endometrial cancer (EC) has important prognostic and therapeutic implications. p53abn EC represent the most aggressive molecular subtype, and recent data has shown a survival benefit from chemotherapy and targeted therapies. We describe the clinicopathologic diversity in presentation and outcomes of p53abn ECs.
Methods Molecular classification was performed on ECs diagnosed in 2016 from 30 Canadian centres. Clinicopathologic and outcome data were collected.
Results 190 ECs were p53abn subtype; 100 serous, 33 endometrioid, 29 carcinosarcomas, 20 mixed, 6 clear cell carcinoma, 2 undifferentiated. 13 p53abn endometrioid ECs were low grade (Gr1/2). There was a trend for worse outcomes with non-endometrioid histotypes(p=0.074). Non-endometrioid p53abn ECs were more likely to present with advanced stage (III-IV) disease compared to endometrioid p53abn ECs (43% vs 15%, p=0.003). There was significant variation in adjuvant treatment; 28% patients received no adjuvant therapy, 40% received no chemotherapy. of the patients who had no chemotherapy, 20/76 (26.3%) had a disease related event (progression/disease specific death). Stage I p53abn low grade ECs had worse outcomes (5-fold) than stage I low grade ECs of all other molecular subtypes combined.
Conclusions p53abn EC was observed across a range of histotypes including low grade ECs, with no significant difference in outcomes based on histotype. EC risk stratification based on histotype and stage failed to identify 25% of patients as high risk and 15% as intermediate risk based on the 2020 ESGO/ESTRO/ESP EC guidelines, which resulted in a missed opportunity for chemotherapy and targeted therapy.
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