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Endometrial cancers with mutations in the proofreading domain of POLE, though hypermutated and often high grade, almost never recur, identifying a group of women who can be spared adjuvant treatment.
Analysis of 788 endometrial cancers from the PORTEC-1 and PORTEC-2 trials for POLE exonuclease domain mutations, found in 6.1 percent, with survival analysis and a meta-analysis of published series.
POLE-mutant tumours were more often high grade yet had excellent recurrence-free survival (hazard ratio 0.14) and cancer-specific survival, independent of other prognostic factors.
POLE sequencing is now part of endometrial cancer classification, and guidelines allow omission of adjuvant therapy for stage I to II POLE-mutated tumours.