Our analysis of the cost-effectiveness of endoscopic ablation of BE demonstrates that ablation of HGD in subjects with BE is probably cost-effective, capable of providing over three years of additional quality-adjusted life expectancy at a cost of less than $6,000 per dQALY gained. Despite biasing the model against ablation, this strategy is estimated to be more effective and less costly than surveillance or esophagectomy for patients with BE and HGD. The effectiveness of the different ablation techniques appears similar, with variation only in costs. In LGD, ablative therapy may be cost-effective compared to surveillance; however, continued endoscopic surveillance of patients after successful reversion to normal squamous epithelium yields little benefit. In the setting of non-dysplastic BE, ablation may be the preferred strategy if the proportion of patients in whom complete and permanent ablation is achieved is greater than 40% (WTP $100,000 per dQALY gained), and endoscopic surveillance can be discontinued in patients in whom ablation is successful.
A goal of decision analysis is to illuminate important gaps in our knowledge and to highlight key questions that must be answered in order to determine whether a proposed intervention should be implemented. In the present analysis, perhaps the single most important “unknown” is the prognosis of subjects who have undergone ablation, and are now endoscopically and histologically normal. Are these patients no longer at risk for developing cancer, and can they be released from endoscopic surveillance? Currently insufficient data exist to answer this question and presently, we and others are retaining these subjects in endoscopic surveillance programs. Because of uncertainty regarding the prognosis of these patients, we modeled both the currently practiced strategy of maintaining surveillance in these subjects, as well as the strategy of releasing successfully ablated patients from surveillance. Recent studies have questioned the benefit of endoscopic surveillance and our analyses illustrate only a nominal benefit of endoscopic surveillance.34
In all scenarios continuation of surveillance after successful ablation is not a preferred strategy. Whether a strategy of selective follow-up of patients based on ablation results can be justified awaits further outcomes data from cohorts having undergone ablative therapy.
Ablative strategies may appear cost-effective either by being superior modes of therapy, or because the comparator strategies are poor interventions. This analysis suggests that endoscopic surveillance may be an especially inefficient and cost-ineffective strategy. Previous studies have demonstrated the poor cost-effectiveness of surveillance to decrease mortality from esophageal adenocarcinoma.35
From a broad perspective, it is more effective (and cost-effective) to prevent cancer than to treat cancer. It is the intent of this analysis not to promote one specific preventive or ablative technique, but rather to highlight the fundamental advantages of interventions that reduce cancer incidence, especially if the complications associated with the intervention are uncommon. This concept is exemplified in the model of no dysplasia. Ablation is preferred in this group, but only if we are willing to forego continued surveillance for patients in whom metaplasia has been eliminated, even if there remains a small risk of progression to malignancy.
The sensitivity analyses illustrate the key factors influential in the decisions regarding management of patients with BE. Common to all scenarios is the dependence of the results on the efficacy of ablation, the durability of these effects and ultimately whether cancer incidence is reduced after ablation is achieved. Thus, the effectiveness and cost-effectiveness of ablative methods will not be fully understood until such data can be accumulated from patients enrolled in research protocols. The costs of various interventions are also influential but rarely change the order of preferred strategies. Other variables, including the risk or cost of complications, the effectiveness of surgery and the preference of patients for various health states (utilities) do not appear to influence the outcomes.
Our analysis has some important limitations. The values used to populate the model were derived from selected groups of patients in most cases referred to specialized centers and prone to selection and publication bias. Because we felt it important to have our model conform to national cancer statistics we calibrated the natural history of the model to the lowest rates of cancer incidence reported in published literature, thereby biasing our results against the use of any intervention. Also, we have assumed that subjects in whom ablation was unsuccessful or in whom metaplasia recurred after ablation retained the cancer risk of their initial level of dysplasia. Some data suggest that a failed attempt at ablation may actually result in the expression of precancerous markers that could potentially put these patients at a higher risk for neoplasia.36
We chose to examine the management of patients with established BE in this study while excluding the question of whether screening to identify this group is cost-effective. Our earlier work compared the relative impact of screening vs. surveillance and found that while screening 50-year old white men with heartburn to detect cancer and dysplasia would likely be cost-effective, continued surveillance of patients without dysplasia was an expensive strategy.35
The current study expands upon this theme in which surveillance is illustrated to be both ineffective and costly, due to the relatively infrequent development of dysplasia and cancer among patients not diagnosed with dysplasia during the initial screening and the inaccuracy of dysplasia as a marker of progression to malignancy. Development and validation of biomarkers that better predict the development of cancer among people with BE would improve the effectiveness of surveillance, as well as enhance selection of patients most appropriate for ablation.37
A greater question raised through these studies is whether any intervention for patients diagnosed with BE without dysplasia is warranted. Based on the marginal differences in cost-effectiveness between ablation and surveillance, perhaps even ablation in non-dysplastic BE requires resources that are beyond the threshold society is willing to expend; however, this study focuses on optimizing management of patients with established BE while our previous work focused comparing the benefit of the initial screen vs. subsequent surveillance to detect early cancer. More broadly, the results of this study are not limited to valuation of endoscopic ablation but rather provide a set of general principles upon which interventions may be compared to current standards of care. The threshold analyses provided in this paper may be used as a benchmark for any future intervention developed to reduce mortality from esophageal adenocarcinoma. The main concept we wish to convey is that strategies that reduce cancer development should be preferred over strategies that rely on early diagnosis of cancer.
Our data are in line with previous studies of cost-effectiveness of ablation for BE compared to either surveillance or esophagectomy.38–41
Although absolute results have varied across studies, these have shown ablation to be superior to comparator arms in the treatment of HGD. Even when ablation is used to treat incident dysplasia identified through surveillance, the recurrent costs of endoscopy, poor reproducibility of histological interpretation and low incidence of cancer in subjects under surveillance combine to make endoscopic surveillance strategies unfavorable, especially in those with non-dysplastic disease.
In conclusion, our data suggest that endoscopic ablation may be the preferred strategy for the management of BE with HGD. Ablation may also be preferred in subjects with LGD and non-dysplastic disease, but the cost-effectiveness of this strategy is highly dependent on the long-term effectiveness of ablation therapy and whether surveillance endoscopy can be discontinued following a successful ablative procedure. As further post-ablation data become available, the optimal strategy to be implemented will be clarified.