Should progesterone and estrogen receptors be assessed for predicting the response to conservative treatment of endometrial hyperplasia and cancer? A systematic review and meta-analysis.

Introduction: Progestins are used as conservative treatment of endometrial hyperplasia (EH) and early endometrial cancer (EEC). We aimed to assess whether immunohistochemical expression of estrogens and progesterone receptors (ER and PR) predicts the treatment response.

Material And Methods: Electronic databases were searched for studies assessing ER and PR expression in EH and EEC treated with progestins. Relative risk for poor response, sensitivity, specificity, diagnostic odds ratio positive and negative likelihood ratios (LR and LR ) and area under the curve (AUC) on summary receiver operating characteristic curve were calculated. Subgroup analyses were based on administration route (oral progestin or levonorgestrel-intrauterine device) and on histological diagnosis (atypical EH/EEC or non-atypical EH). Only high accuracy (AUC > 0.9; LR  >10; LR  <0.1) was considered determining for the clinical practice.

Results: Thirteen studies with 635 patients were included in the systematic review. Studies at high risk of bias were excluded from the meta-analysis. Negative ER expression did not significantly predict poor response (P = 0.16), with low predictive accuracy (AUC = 0.637). Negative PR significantly predicted poor response (P = 0.01), with moderate accuracy (AUC = .806). In the oral progestin subgroup, neither ER (P = 0.55) nor PR (P = 0.18) had significant predictive value. In the levonorgestrel-intrauterine device subgroup, both ER (P < 0.0001) and PR (P = 0.02) were significantly predictive of good response, although the accuracy was suboptimal (LR 6.02 and 2.48, respectively; LR 0.59 and 0.55, respectively). The atypical EH/EEC subgroup showed non-significant results. Data about non-atypical EH were not extractable.

Conclusions: ER and PR expressions are significantly predictive of response in EH and EEC treated with a levonorgestrel-intrauterine device but not with oral progestins. However, their accuracy is insufficient to be determining in the clinical practice.