ObjectiveTo observe the effect of systemic chemotherapy on conditions of tumor infiltrating,metastasis and disease-specific survival (DSS) for advanced retinoblastoma (RB). MethodsForty-one patients with advanced RB who received enucleation were enrolled in this study. There were 26 males and 15 females, age at diagnosis was ranged from 2 to 72 months, with a mean of 23.08 months. There were 16 bilateral patients and 25 unilateral patients; 13 group D eyes and 28 group E eyes. 16 patients received enucleation as the primary treatment (operation group), 25 eyes received chemotherapy before enucleation (chemotherapy group). There was no significant statistical difference between two groups for the gender, unilateral and bilateral, international staging or diagnostic age (P>0.05). The histopathology report was performed to assess the risk of postoperative tumor-node-metastasis staging (pTNM) in each patient, and the extent of tumor invasion in the optic nerve, choroid and anterior chamber was divided into 3 levels of low risk, medium risk and high risk. Five deaths were all in the group E with chemotherapy before enucleation. Using R software survival analysis software package survfit function, the application of Kaplan-Meier estimation method, DSS of RB children was calculated from the time of diagnosis, up to the date of the death of patient. DSS differences between chemotherapy, operation group and eye removal time (more than 3 months, less than 3 months) in group E RB children were analyzed. ResultsThe proportion of high risk pTNM stage in chemotherapy group was significantly lower than the operation group. But there was no significant difference between the two groups in the overall risk classification (χ2=3.130,P=0.077). For group D eyes, the overall risk classification in chemotherapy group was significantly lower than the operation group (χ2=5.870,P=0.015). There was no significant difference between the two groups in the overall risk of group E eyes (χ2=0.020,P=0.889). The DSS in chemotherapy group and operation group were 0.71 and 1.00, respectively; the difference was significant (χ2=3.700,P=0.05). The DSS in children whose enucleation delayed for more than 3 months and children whose enucleation performed within 3 months were 0.64 and 1.00, respectively; the difference was significant (χ2=4.800,P=0.028). ConclusionSystemic chemotherapy did not reduce the risk of tumor invasion and metastasis in patients with advanced RB. Instead, it will reduce the DSS in group E eyes of RB.