Residual disease volume and prognosis in endometrioid precancer after progestin therapy

Progestin therapy is a conservative treatment option for atypical hyperplasia/endometrioid intraepithelial neoplasia (AEH/EIN), particularly for patients seeking fertility preservation or for whom surgery is not feasible. However, approximately 30% of patients exhibit resistance to therapy, underscoring the need for early identification of responders and non-responders. We conducted a retrospective study of 252 AEH/EIN patients who underwent progestin therapy, with serial follow-up endometrial biopsies yielding 892 samples with quantifiable residual disease (RD). The amount of RD was evaluated as a predictor of therapeutic response, with a focus on its prognostic significance. Among the 252 patients, 194 (77%) were classified as responders, while 58 (23%) were non-responders. Responders exhibited a progressive reduction in RD across follow-up biopsies, with all achieving complete decidualization by the final biopsy. In contrast, non-responders consistently demonstrated persistent RD, with more RD in initial biopsies post progestin therapy significantly correlating with non-response. An amount of RD exceeding 20% in the initial biopsy or a less than 50% reduction in subsequent biopsies strongly predicted therapeutic failure (p < 0.001). The amount of RD is a valuable predictive marker for progestin therapy outcomes in AEH/EIN patients. Incorporating RD volume assessment in pathology reports can enhance clinical decision-making, facilitating more personalized and effective treatment strategies. Early identification of non-responders may prevent prolonged ineffective therapy and enable timely alternative interventions.