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Endometrial Cancer — SCE Medical Oncology MCQ

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ModerateGynaecological CancersEndometrial CancerSCE Medical Oncology

A 65-year-old woman with stage IIIC endometrial cancer undergoes molecular classification. She is found to have a POLE exon 9 and 13 hotspot mutation (ultramutated phenotype). Despite high-risk staging, what does this molecular classification indicate?

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Correct answer: A — Excellent prognosis — POLE ultramutated endometrial cancer has the best outcomes regardless of grade or stage, potentially allowing de-escalation of adjuvant therapy

POLE ultramutated endometrial cancer has the best prognosis of all four molecular subtypes (<5% recurrence rate even in high-grade/high-stage disease). This is now incorporated into FIGO 2023 staging (lowering the effective stage). The PORTEC-4a trial is evaluating de-escalation of adjuvant therapy based on molecular classification. The RAINBO and TAPER trials are also addressing whether POLE-mutated tumours can safely omit adjuvant chemotherapy/radiotherapy. This is a paradigm shift from purely histological risk stratification.

Reference: ESMO 2024 Endometrial Cancer Guidelines; FIGO 2023 Staging; PORTEC-4a