TACE is the treatment of choice for inoperable tumours that are too large or multifocal for other percutaneous ablation techniques such as radiofrequency ablation (RFA). Some studies show TACE combined with sorafenib or apatinib get a longer TTP, OS and tumour-response rate[28, 34]. Recently, SBRT has emerged as a safe and effective solution for properly selected patients with HCC having excellent rates of local control rate[12], one review study demonstrated that SBRT is an adjunct to TACE and sorafenib, a substitute for RFA[35]. One meta-analysis showed TACE combined with SBRT was more effective than TACE alone[17]. However, due to China imbalanced financing in different area, the high cost of SBRT used for treating patients of inoperable HCC have become one of the biggest issues, the decision-maker is probably willing to pay for the cost-effective solutions. To the best of our knowledge, this is the first study to compare the cost-effectiveness of TACE plus SBRT versus TACE. The result will provide evidence in determining a reasonable reimbursement decision and price.
In our study, TACE plus SBRT is cost-effective compared to TACE for inoperable based on the base case analysis, sensitivity analysis and WTP analysis. Previous CE studies have confined the comparison of TACE with sorafenib, TACE alone is a more cost-effective strategy from Chinese perspective. And SBRT with other solutions such as sorafenib, RFA, proton beam therapy[32, 36–39], SBRT is cost-effective comparing sorafenib and RFA in early and late-stage HCC, respectively. One other outcome research studies compared the SBRT plus TACE with SBRT[40], which also showed that the combination of TACE plus SBRT achieved higher objective response and local control rate. Our study chose a different comparator TACE, which is wildly referenced in clinical guidelines and practiced. This study demonstrated that TACE plus SBRT is a wise choice for the patients at stage IIIa or IIIb and not suitable for surgery.
We tested the stability of the results with various sensitivity analyses, which showed that the results were robust. Several key parameters are impacted on the cost-effectiveness results. One is the utility of progression survival for TACE plus SBRT, it is well known for adverse events of SBRT including fatigue, damage to the liver, gastrointestinal tract, and biliary duct, cytopenia, dermatitis, and rib fractures. We found that there is a higher rate for TACE plus SBRT, therefore, we assumed the utility of patients in each state was lower. Another parameter is the probability of death from progress survival in TACE. When the reduction by 30% of TACE, the ICER is enhanced by 75%. Finally, the cost of TACE plus SBRT is also a parameter that affects the results. In China, different regions can decide their price of health service, so there is a lot of variances. Because SBRT is technology-based, the cost is basically the same according the price system. So we subtract the cost data from Chinese research and set the range for it.
Data constraints inevitably lead to several limitations within our model. First, there were no multi-centered RCT studies that specifically reported TACE plus SBRT outcomes for inoperable HCC. Such a limitation was unfortunately unavoidable in this analysis. This limitation obliged us to use the best available data in the literature review. The resulting uncertainties were not significant, which was confirmed by the unchanged results in the probabilistic sensitivity analysis. Second, the utility estimates were extracted from the CEA registry. This adoption may not be the most rational because utilities might vary between populations. The third limitation concerns the paucity of data on cost estimates for each health state. There were no cost data for TACE plus SBRT, so we collected it separately and combined it, this may be different from the real world. Moreover, we have considered the uncertainties of costs in sensitivity analyses by inputting a wide range of cost values (-30–30% of base-case value). Fourth, we assumed that the utility estimations such as PFS and progression survival were different between two groups and set a lower value for TACE plus SBRT, however, there might be the same or higher. Thus, more specific data are required to obtain more accurate results for it. Fifth, most of the included studies were retrospective and the analyses based on these retrospective data would inevitably result in selection bias.