Assessing the New 2020 ESGO/ESTRO/ESP Endometrial Cancer Risk Molecular Categorization System for Predicting Survival...

Area of Science:

• Gynecologic Oncology
• Molecular Pathology
• Cancer Genomics

Background:

• Endometrial cancer (EC) management relies on risk stratification.
• Existing guidelines from the European Society of Medical Oncology (ESMO) have limitations.
• The 2020 European Society of Gynecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) guidelines introduced molecular classifications.

Purpose of the Study:

• Evaluate the efficacy of the 2020 ESGO/ESTRO/ESP guidelines for endometrial cancer.
• Introduce and assess a novel risk category incorporating clinicopathological and molecular factors.
• Compare the new classification with prior ESMO risk stratifications in Korean EC patients.

Main Methods:

• Categorized EC patients into POLE-mutated (POLEmut), mismatch repair-deficient (MMRd), p53-aberrant (P53abn), and nonspecific molecular profile (NSMP) subtypes.
• Assessed recurrence, survival, and adjuvant therapy based on molecular and guideline classifications.
• Utilized immunohistochemistry for TP53 and MMR, alongside POLE sequencing.

Main Results:

• POLEmut subtype showed no relapse; P53abn subtype had high recurrence (31.8%) and mortality (31.8%).
• The 2020 ESGO/ESTRO/ESP guidelines identified 33.3% of low-risk patients as potentially overtreated.
• Significant differences in overall and progression-free survival were observed across molecular subtypes, with POLEmut faring best and P53abn worst.

Conclusions:

• The 2020 ESGO molecular classification system is practically useful and significantly impacts endometrial cancer survival outcomes.
• Molecular risk categories, identified through TP53/MMR IHC and POLE sequencing, are clinically relevant for EC management.
• Personalized risk stratification improves treatment decisions and patient outcomes in endometrial cancer.