Intravenous chemotherapy versus intra-arterial chemotherapy for retinoblastoma.
This Cochrane review of six pediatric retinoblastoma studies found moderate-certainty evidence from one RCT that intra-arterial chemotherapy probably improves globe salvage versus intravenous chemotherapy without a demonstrated overall-survival difference, while evidence for adding intravenous chemotherapy to intra-arterial therapy was largely low or very low certainty.
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This Cochrane review of six pediatric retinoblastoma studies found moderate-certainty evidence from one RCT that intra-arterial chemotherapy probably improves globe salvage versus intravenous chemotherapy without a demonstrated overall-survival difference, while evidence for adding intravenous chemotherapy to intra-arterial therapy was largely low or very low certainty.
Research significance
Evidence supports the hypothesis that first-line intra-arterial chemotherapy may improve eye preservation compared with intravenous chemotherapy in children with retinoblastoma; inferring a preferred regimen or added value from combined intravenous and intra-arterial treatment remains premature because survival, toxicity, recurrence, metastasis, and long-term outcomes are uncertain or inadequately reported.
Source abstract
BACKGROUND: Intra-arterial chemotherapy (IAC), intravenous chemotherapy (IVC), and the combination of both (IVC + IAC) are among the most important treatment options for retinoblastoma, a rare form of childhood cancer. The outcomes of previous studies evaluating the success rates of these methods have been discrepant due to the varying quality of the research as well as the different study types, sample sizes, and definitions of outcomes. OBJECTIVES: To assess the benefits and harms of IAC, IVC, and the combination of both, in people with retinoblastoma. SEARCH METHODS: We searched CENTRAL, MEDLINE, and Embase in September 2025. No search filters or restrictions regarding language or year of publication were used. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) comparing either first-line IAC versus IVC or IVC + IAC versus IAC in children and adults with a confirmed diagnosis of retinoblastoma, irrespective of disease severity, gender, or ethnicity. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. We assessed the certainty of the evidence using GRADE. Our main outcomes were tumor control with the avoidance of enucleation or external beam radiation therapy (EBRT), globe salvage (overall), overall survival, secondary neoplasms, tumor recurrence, development of metastasis, and the number of grade 3 and grade 4 adverse events at the end of short-term (< 1 year), medium-term (< 3 years), and long-term (> 3 years) follow-up. MAIN RESULTS: We included six studies, of which three compared IAC with IVC (one RCT and two NRSIs) in 210 participants and 214 eyes. The other three studies compared IVC + IAC with IAC (three NRSIs) in 599 participants and 681 eyes. All participants in the included studies were children. The main results presented refer to a medium-term follow-up (up to three years). IAC versus IVC Findings of the RCT IAC compared to IVC probably increases globe salvage (overall) (hazard ratio (HR) 2.01, 95% confidence interval (CI) 1.17 to 3.45; IVC: 260 per 1000; IAC: 454 per 1000 (95% CI 297 to 646/1000); 1 RCT, 143 eyes; moderate-certainty evidence). IAC compared to IVC probably results in little to no difference in overall survival (HR 0.97, 95% CI 0.20 to 4.80; IVC: 950 per 1000; IAC: 951 per 1000 (95% CI 769 to 989/1000); 1 RCT, 143 eyes; moderate-certainty evidence). IAC compared to IVC may result in little to no difference in tumor recurrence (RR 0.91, 95% CI 0.45 to 1.86; IVC: 180 per 1000; IAC: 164 per 1000 (95% CI 81 to 335/1000); 1 RCT, 143 eyes; low-certainty evidence). IAC compared to IVC may result in little to no difference in the number of grade 3 and grade 4 adverse events (1 RCT, 143 eyes; low-certainty evidence). Limitations of the evidence are a high risk of bias and serious imprecision. No other prioritized endpoints were reported in the RCT. Findings of the NRSI The evidence is very uncertain about the effect of IAC compared to IVC on tumor control with avoidance of enucleation or EBRT (1 NRSI, 23 eyes; very low-certainty evidence). Secondary neoplasms were not reported. IAC compared to IVC may have little to no effect on the development of metastasis, but the evidence is very uncertain (1 NRSI, 19 participants; very low-certainty evidence). Limitations of the evidence are an assessment of serious risk of bias and serious imprecision. Additional outcomes are shown in the results section. IVC + IAC versus IAC IVC + IAC compared to IAC may have little to no effect on tumor control with the avoidance of enucleation or EBRT, but the evidence is very uncertain (1 NRSI, 98 eyes; very low-certainty evidence). IVC + IAC compared to IAC may result in little to no difference in globe salvage (overall) (RR 0.96, 95% CI 0.89 to 1.03; IAC: 791 per 1000; IVC + IAC: 758 per 1000 (95% CI 703 to 814/1000); 3 NRSIs, 681 eyes; low-certainty evidence). IVC + IAC compared to IAC may result in little to no difference in overall survival (RR 1.02, 95% CI 0.98 to 1.07; IAC: 925 per 1000; IVC + IAC: 944 per 1000 (95% CI 904 to 990/1000); 3 NRSIs, 599 participants; low-certainty evidence). Secondary neoplasms were not reported. The evidence is very uncertain about the effect of IVC + IAC compared to IAC on tumor recurrence (3 NRSIs, 681 eyes; very low-certainty evidence) and on the development of metastasis (3 NRSIs, 599 participants; very low-certainty evidence). The evidence is very uncertain about the effect of IVC + IAC compared to IAC on the number of grade 3 and grade 4 adverse events (2 NRSIs, 386 participants; very low-certainty evidence). Limitations of the evidence are an assessment of serious risk of bias, serious inconsistency, and serious imprecision. Additional outcomes are shown in the results section. AUTHORS' CONCLUSIONS: Due to the lack of randomized studies comparing first-line IAC with IVC and first-line IVC + IAC with IAC, most of the included studies are not masked (blinded) and are retrospective in design, which may lead to bias. IAC versus IVC IAC compared to IVC probably increases globe salvage (overall), probably results in little to no difference in overall survival, may result in little to no difference in tumor recurrence, and may result in little to no difference in the number of grade 3 and grade 4 adverse events. IVC + IAC versus IAC IVC + IAC compared to IAC may result in little to no difference in globe salvage (overall) and may result in little to no difference in overall survival. Overall Currently, there are mostly only retrospective, non-randomized studies on this topic with only a few randomized studies. More randomized studies with a higher number of study participants and comparable long-term results are needed to be able to determine the effect of IAC compared to IVC, or IVC + IAC compared to IAC, in people with retinoblastoma. There is an urgent need to develop a standardized and internationally valid nomenclature of endpoints to achieve greater homogeneity and clearer, comparable results.