PurposeCurrently, there are no reliable indicators for the early identification of patients with low-risk gestational trophoblastic neoplasia (GTN) who develop resistance to monotherapy. This study aimed to evaluate the effectiveness of combining the Systemic Immune-Inflammation Index (SII) and Prognostic Nutritional Index (PNI) in detecting early resistance to monotherapy in patients with low-risk GTN.MethodsThis retrospective study included 91 patients with low-risk GTN who received initial monotherapy at Fujian Maternal and Child Health Hospital between 2013 and 2021. The SII and PNI before chemotherapy were calculated from prechemotherapy peripheral blood samples, with cut-off values determined by receiver operating characteristic (ROC) curves. The SII-PNI score ranged from 0 to 2 points and was categorized as follows: a score of 2 points indicated a high SII (≥467.02) and a low PNI (≤51.35); a score of 1 point indicated either a high SII or a low PNI; and a score of 0 points indicated neither a high SII nor a low PNI.ResultsNinety-one patients with low-risk GTN underwent monotherapy, 19 of whom developed resistance, whereas the remaining 72 did not. The SII was significantly greater in chemotherapy-resistant patients than in non-resistant patients (P=0.04), whereas the PNI was markedly lower in chemotherapy-resistant patients (P=0.002). Univariate analysis revealed that cut-off values of 467.02 for the SII (P=0.04) and 51.35 for the PNI (P=0.024) were associated with chemotherapy resistance in patients with low-risk GTN. As the SII-PNI score increased, the proportion of chemotherapy-resistant patients increased (P<0.001), and the time for human chorionic gonadotropin (hCG) normalization correspondingly increased (P<0.001). Multivariate logistic regression analysis indicated that a high SII-PNI score is an independent risk factor for chemotherapy resistance in patients with low-risk GTN (P=0.001).ConclusionA high SII and low PNI are linked to chemotherapy resistance in patients with low-risk GTN. The pretreatment SII-PNI score is a key indicator for predicting the sensitivity of patients with low-risk GTN to single-agent chemotherapy, aiding in the early identification of individuals at high risk of resistance.