Fertility-Sparing Treatment of Endometrial Cancer and Atypical Endometrial Hyperplasia by Molecular Classification: A Systematic Review and Meta-Analysis Accounting for Outcome-Assessment Timing and Follow-Up Duration

Abstract

Simple Summary Some younger women with early cancer of the womb lining, or its precursor (atypical hyperplasia), wish to preserve the possibility of having children and can be offered hormone treatment instead of surgery to remove the womb. Doctors increasingly use a tumour’s molecular “type” to estimate how such treatment is likely to go, but published findings have been inconsistent. By combining data from 15 published patient groups, we found that comparisons between molecular types depend heavily on when the response is assessed and on how long patients are followed. In every type, many women who had not responded at six months responded later. Tumours with a mismatch-repair defect responded less often and more slowly and relapsed early; in the largest, “no specific profile” group, relapse tended to accumulate with longer follow-up, although this depended on which long-term studies were included; the rare POLE-mutated tumours responded well, but their long-term durability is uncertain; and p53-abnormal tumours raised concern about durability. About one in six women selected on conventional criteria carried a p53-abnormal or mismatch-repair–deficient tumour. Molecular testing therefore seems most useful for identifying these higher-risk tumours before treatment and for planning follow-up, rather than for relaxing monitoring in apparently favourable cases.