Introduction Gestational trophoblastic neoplasia (GTN) is usually a chemo-responsive malignancy. However, some patients do not respond to single-agent chemotherapy despite their risk score being <6 (low-risk). Identifying risk factors for the same may help change the current scoring system, potentially prompting the initiation of multi-agent chemotherapy from the outset for these patients.

Methods This was a single-centre, retrospective, cross-sectional analytical study. All cases of low-risk GTN were included in the study period from January 2010 to December 2022. The baseline factors were compared between those who developed resistance to first-line single-agent chemotherapy with methotrexate and those who did not.

Results Eighty cases were included. The response rate to first line methotrexate monotherapy was 80%. Notably, the response rate reached 100% when the risk score was 1. However, an increased risk of chemoresistance was observed when the score was ≥4 (odds ratio [OR] = 1.8, 95% confidence interval [CI] 0.56-5.89, p = 0.8). There was a notable trend towards higher odds of developing chemoresistance beyond a 7-month interval from the antecedent pregnancy (OR = 9, 95% CI 0.76-106.33, p = 0.07). No other factors significantly contributed to the development of chemoresistance to methotrexate. Among the chemo-resistant cases, 2 patients responded to Actinomycin D as the second-line chemotherapy.

Conclusion/Implications No sociodemographic, clinical, or biochemical factor was significantly associated with the development of chemoresistance to methotrexate. However, these results could be due to sample size limitations. Future research with larger sample sizes and prospective study designs could provide deeper insights into the predictors of chemoresistance in low-risk GTN cases.