The value of an initial drop in Human Chorionic Gonadotropin levels in predicting a response to methotrexate in women with low-risk Gestational Trophoblastic Neoplasia

Objectives: The early identification of patients who are being treated for low-risk gestational trophoblastic neoplasia (LRGTN) with single-agent chemotherapy, who are at high risk of developing chemoresistance, is of crucial importance.The aim of our research was to evaluate the pretreatment beta subunit of human chorionic gonadotropin (beta hCG) concentration and its decrease after the administration of the first course of methotrexate (MTX) in predicting later chemo-resistance to single-agent chemotherapy. Material and Methods: A total of 46 patients diagnosed with LRGTN treated with a 5-day methotrexate (MTX) regimen were retrospectively studied. 24 of the patients were successfully cured with only MTX therapy (MTX group).The disease was considered resistant in the remaining 22 patients who, after MTX therapy, required further chemotherapy with an EMA/CO regimen (EMA/CO group). To compare changes in the beta hCG concentrations between the two courses of treatment (and the two groups), we calculated the percentage of decline. We determined the specificity and sensitivity of the initial beta hCG level and its percentage decline, as a potential predictor of the need for a future EMA/CO regimen. For diagnostic purposes, beta hCG levels were measured before the first and second administrations of MTX with a commercial ELISA kit. Results: In the EMA/CO group, we found the initial beta hCG level before the first MTX dose was higher (median = 6275 mIU/mL, range: 21.53-192.610.0 mIU/mL) than in the MTX group (median = 532 mIU/mL, range: 56.5 mIU/mL-360.397.0 mIU/mL) (p = 0.034, Mann-Whitney test). The percentage decreases in the beta hCG values relative to the initial concentrations were higher in the MTX group (median decrease = 82.7%, range: from 13.3% to 99.9%) than in the EMA/CO group (median decrease = 71.1%, range: from an increase of 56.1% to a decrease of 97.1%) (p = 0.0079, Mann-Whitney test). An analysis of the ROC curves implied optimal cutoff values for the initial beta HCG (6054 IU, sensitivity = 55%, specificity = 86%) and the percentage change in beta hCG levels (decrease by 76.5%, sensitivity = 72%, specificity = 71%). Conclusions: 1. Women with initially higher beta hCG levels have a greater risk of developing MTX chemo resistance. 2. It would be advantageous to consider administering an EMA/CO regimen in women with LRGTN when their initial beta hCG levels are greater than 6000.