IO Learning invited Nishita Kothary, MD, to discuss her 2020 Society of Interventional Radiology (SIR) abstract, “Comparison of Drug-Eluting Beads versus Conventional Transarterial Chemoembolization: A Cost-Effectiveness Analysis.”1 The study based on this abstract has been published in the Journal of Vascular and Interventional Radiology.2
What led you and your co-authors to investigate the cost-effectiveness of cTACE vs DEB-TACE?
Dr Xiao Wu, the first author of this study, did the lion’s share of the work. Xiao is now an interventional radiology-diagnostic radiology (IR-DR) resident at UCSF, but she came to Stanford for an elective away-rotation from Yale. She and her mentor Dr Ajay Malhotra (neuroradiologist at Yale), have an impressive track record on cost-effective analysis. So it was fortuitous that we met, and I have Dr Chapiro (Yale IR) to thank for that. Xiao heard me complain about the myriad ways we perform transarterial chemoembolization (TACE) without any proven benefit of one over the other. My other passion is cost, and the progressively increasing cost of TACE (or any locoregional therapies) has always bothered me. We have had a long-standing debate over conventional TACE (cTACE) vs drug-eluting embolic (DEB)-TACE. Five or 6 years ago, DEB-TACE became very popular due to a constant shortage of Lipiodol (Guerbet), a poppyseed oil used for cTACE as an emulsifying agent for cisplatin. DEB-TACE, on the other hand, comes as a single product and is readily available. During the cisplatin and Lipiodol shortage, interventional radiologists became accustomed to DEB-TACE, and many never switched back to cTACE after Lipiodol became available again.
Over the years, authors have published randomized, prospective trials, and other large cohort studies that compared the clinical outcomes for both products. None of these studies have shown statistical differences between the two. Overall outcomes, including response and overall survival, are similar. One study showed that DEB-TACE had significantly fewer adverse events than cTACE, but that was a post hoc analysis, and the benefit was only apparent in a select group of patients. We therefore decided to bring in a third variable, which is cost. At one time, DEB-TACE was markedly (approximately 10 times) more expensive than cTACE, although that difference is much smaller now. Doxorubicin, used in cTACE, is a commonly used chemotherapeutic agent and is relatively inexpensive. Lipiodol, the other component of cTACE, was used for other applications such as lymphangiograms and was also reasonable in the past as it is merely poppyseed oil. Therefore, the combination of doxorubicin with Lipiodol (sometimes with mitomycin and/or cisplatin) was still a cheaper option than using doxorubicin-eluting embolics. However, the cost of Lipiodol has increased dramatically over the past few years. The substantial price increase for Lipiodol was the main driver of this analysis, as the two therapies are now on a more level playing field in terms of cost.
What were the study results?
Our results were very interesting. We found that even with the increase in cTACE pricing, it was still less expensive than DEB-TACE when we looked at the quality-adjusted life-year (QALY). Every time somebody gets sick, there is a cost to that sickness. Our analysis takes into consideration both the absolute costs and the QALY associated with those costs. We used Monte Carlo modeling and examined multiple scenarios to simulate real-life situations. For example, let’s say a patient is hospitalized with adverse events after TACE, and their quality of life suffers. Since patients usually undergo multiple treatments in real life, we also examined the impact of additional procedures, such as another ablation, radioembolization, etc. Based on our modeling results, cTACE fared better. We found that despite the notion that DEB-TACE was associated with fewer adverse events, cTACE still had a better QALY score than DEB-TACE (2.11 vs 1.71, respectively). Another notable result was that cTACE is more cost effective when mortality risk is below 17% per 3-month interval, independent of mortality after DEB-TACE. In other words, for DEB-TACE to reach an equivalent cost effectiveness, the cTACE mortality (eg, adverse events, unsuccessful treatments, etc) would have to exceed DEB-TACE mortality by 17%. None of the prior studies have shown a statistical significance or even a trend for that level of difference. Therefore, it would be quite a stretch for DEB-TACE to become cost effective just by a decrease in mortality. Chemoembolization studies don’t often report on overall survival (OS), because it’s challenging to measure OS in hepatocellular carcinoma (HCC) patients, who have underlying liver disease and many other comorbidities. The Monte Carlo model randomized 10,000 scenarios, and showed that DEB-TACE would only be more cost-effective than cTACE if it could offer an absolute increase of ≥2.5% higher overall survival. Again, studies have not shown this difference in mortality between the two strategies. Therefore, we believe that cTACE is here to stay and is the presumptive cost-effective strategy.
Were you surprised by the study results?
To a certain extent. Historically, Stanford has always been a big proponent of cTACE. For super-selective, cone-beam CT-assisted TACE, I believe cTACE has advantages, including visibility of the delivered emulsion. Some in the interventional radiology community feel that DEB-TACE is more effective, but we have not seen that pan out in our clinical practice, nor have my colleagues at Yale. I trained at UPenn, and I believe they still use cTACE. My point is that many of these large academic centers continue to use cTACE, so I wouldn’t say I was terribly surprised, but I was pleasantly surprised. The results validated what I believe regarding the two procedures’ equivalency and that there is no real direct benefit in using DEB-TACE.
Do your study results have implications in a real-world setting?
By 2025, approximately 20% of our GDP will be devoted to healthcare costs. That is money from our schools, roads, military. As gatekeepers, I think we need to be very careful when choosing between available therapies if the results are equivalent. The theme of our study is that if one believes that cTACE and DEB-TACE have equivalent results, even taking adverse effects into account, then one should use the less-expensive option.
Can you comment on future directions for cTACE and DEB-TACE?
A significant advantage of cTACE is that Lipiodol is iodinated and accumulates in the tumor and shines like a beacon to show the operator whether they have treated the entire tumor. The commonly used drug-eluting microspheres lack this capability. Some manufacturers are trying to combine the best of both worlds, ie, to create products that concentrate in the tumor, are easily visible, and elute chemotherapeutic agents. The efficacy of these products is yet to be determined in large studies. But, my biggest concern is their price tag. These products are a level higher than even current DEB-TACE options, indicating that the cost of DEB-TACE will keep rising without any documented, reproducible superiority data. I hope that IRs take these current data into consideration before going for the latest and the greatest. I also hope that companies keep cost-reduction strategies in mind because costs cannot continue to escalate. Obviously, if a product comes on the market that does combine the best of both worlds and is also clinically superior — then yes, the additional dollars would be worth it. So far, that has not been the case.
Do you think your trial results will affect SIR guidelines for TACE?
SIR guidelines in the past have focused on clinical efficacy, much more than cost-effective analyses. But this is changing. And I believe IRs will change as they become more aware of the impact of these costs on their practices and incomes. Of course, the hope is that we, as a group, become savvier about the healthcare cost explosion and champion the idea of value-based cost-effective treatments.
Do you have plans for related future studies?
My next step is to look at the cost-effectiveness of combined chemoembolization and ablation (TACE-ablate) versus radiation segmentectomy (radioembolization) for hepatocellular carcinoma. The Northwestern data showed that fewer treatment sessions were needed with segmentectomy (didn’t demonstrate OS benefit). Unfortunately, there are no randomized control trials that show the same. Still, it would be interesting to see if the higher cost of radioembolization can be offset by lower overall (lifetime) costs.
1. Wu X, Chapiro J, Malhotra A, Kothary N. Comparison of drug-eluting beads versus conventional transarterial chemoembolization: a cost-effectiveness analysis. 2020 SIR abstract poster #533. Available at http://www.sirmeeting.org. Accessed on 2020 June 11.
2. Wu X, Chapiro J, Malhotra A, Kothary N. Comparison of drug-eluting embolics versus conventional transarterial chemoembolization for the treatment of patients with unresectable hepatocellular carcinoma: a cost-effectiveness analysis. J Vasc Interv Radiol. 2020 Nov 4;S1051-0443(20)30805-8. Online ahead of print.
Address for Correspondence: Nishita Kothary, MD, Stanford University Medical Center H3630, Dept of Interventional Radiology, 300 Pasteur Drive, Stanford, CA 94305. Email: firstname.lastname@example.org