Introduction/Background Gestational trophoblastic neoplasm(GTN) which is categorized as low-risk and high-risk,is a rare disease by itself. Most low-risk GTN patients are treated with single-agent chemotherapy;however, the multi-agent protocol is the first choice of treatment for high-risk GTN patients.This study aimed to assess the causes of resistance in low-risk GTN patients undergoing single-agent chemotherapy.

Methodology In this case-control study,we evaluated 207 low-risk GTN patients who were diagnosed and treated at the Oncology Department of referral hospitals in Tehran,Iran between 2011 and 2017. Patients with FIGO stage I were considered as low-risk and standard pulse methotrexate(MTX) or pulse actinomycin-D was started for them.In cases of resistance to first-line single-agent chemotherapy, second-line single-agent and if still resistant, multi-agent chemotherapy with EMA-CO(etoposide, methotrexate, actinomycin D, cyclophosphamide, oncovin)was used. Data were analyzed by SPSS version 22

Results Among all patients,152(73.4%) responded to single-agent chemotherapy, 24 (11.6%) responded to second-line chemotherapy and 31 (15%) required multi-agent chemotherapy.Four cases underwent emergent hysterectomy due to uterine rupture which have been excluded.Significant difference in mean tumor size and FIGO score was found among the three groups of first-line single-agent,second-line single-agent and multi-agent responders;however,response to treatment was not correlated with many factors such as level of Β-HCG(B-Human Chorionic Gonadotropin)and duration of treatment.Univariate analyses showed that many clinical features such as tumor size (P<0.001) and Β-HCG>40,000 accompanied by tumor size ≥ 5 cm (P=0.005) were significantly correlated with the risk of resistance to single-agent chemotherapy.

Conclusion Although more research is needed to suggest multi-agent chemotherapy administration from the beginning for low risk GTN patients at risk for chemotherapy resistance, factors such as tumor size>5 cm accompanied with B-HCG>40000 and FIGO score ≥ 4 can alarm the clinician to better predict possibility of chemotherapy resistance and keep an eye on the patients until normal B-HCG levels are achieved.