Predictive factors associated with resistance to initial methotrexate treatment in women with low-risk gestational trophoblastic neoplasia

Aim: To compare clinical characteristics and identify factors predictive of resistance to initial treatment with methotrexate-folinic acid (MTX-FA) in women with low-risk gestational trophoblastic neoplasia (GTN).

Methods: Retrospective chart reviews were conducted in patients diagnosed with low-risk GTN who were treated with MTX-FA at Siriraj Hospital between 2002 and 2018. Demographic data, disease characteristics, treatment response, toxicity, and data of the subsequent pregnancy were collected and analyzed. Groups of patients who were responsive or resistant to treatment were compared. Stepwise logistic regression analysis was used to identify factors predictive of resistance to methotrexate chemotherapy.

Results: Totally, 113 patients were eligible for analysis. The primary remission rate was 55.8% with first-line MTX-FA. All other patients achieved remission by subsequent treatment with actinomycin D or multiple-agent chemotherapy. Relapse of disease occurred in 4.4% and the overall survival rate was 99.1%. Univariate analysis showed that pretreatment serum hCG, neutrophil-to-lymphocyte ratio at baseline, and serum hCG ratio of the first three consecutive cycles (C) were significantly associated with resistance to MTX-FA. Independent factors that predict failure to respond to first-line MTX-FA were pretreatment serum hCG ≥15,000 IU/L, a less than 4.8-fold reduction of serum hCG between cycle 1 and cycle 2 (C1/C2), and a less than seven-fold reduction of serum hCG from cycle 2 to cycle 3 (C2/C3).

Conclusions: First-line MTX-FA treatment is effective in 55.8% of patients. Pretreatment serum hCG, and serum hCG ratio between consecutive treatment cycles can predict initial treatment failure.