Our model suggests that endoscopic ablative therapy provides a longer quality adjusted life expectancy than either endoscopic surveillance or elective oesophagectomy for those with BO and HGD. Ablative therapy avoids the large upfront costs and considerable morbidity and mortality of surgery. Additionally, unlike endoscopic surveillance, it prevents at least some portion of those destined to develop cancer from progressing to this costly state. Even if ablative therapy is much less effective than has been reported in averting cancer, the incremental cost effectiveness of this strategy still remains well below $50 000 (€41 000) per quality adjusted life year saved.
Although endoscopic surveillance was less expensive than ablative therapy, it was also less effective. Because an additional life year gained with endoscopic ablative therapy is less expensive than a life year gained with endoscopic surveillance, the model suggests that ablative therapy should be the strategy of choice for most payers. This is especially true when one considers that the model mandates continued surveillance endoscopy for all subjects who undergo ablation, whether or not it is successful. Continued endoscopic surveillance in the ablation arm adds additional costs and biases the model against ablation. The model was constructed in this fashion to replicate current practice among those performing ablation but further data may suggest that those who undergo successful ablation do not require continued surveillance. The model was further biased against endoscopic ablative therapy by assuming that all surgical oesophagectomies were done in high volume proficient medical centres. Recent data suggest that results in smaller lower volume centres are much less favourable.25–27
The presence of extended dominance of endoscopic ablation over endoscopic surveillance has interesting ethical implications. If a payer has limited resources, is it better to give a select few subjects a more effective therapy (that is, ablative therapy) or a larger number of patients a less effective therapy (that is, endoscopic surveillance)? In this case, from a utilitarian perspective, it would be logical to give the smaller number of subjects the more effective therapy as the overall life years gained per dollar spent is maximised with this strategy. However, such rationing of healthcare is neither palatable nor egalitarian. As healthcare dollars are not limitless, and expensive therapies for many diseases continue to proliferate, decisions such as which strategy to use in BO with HGD will need to be considered in the larger perspective of society’s willingness to pay for such treatments.
This model has several important strengths. Unlike previous decision analysis models of BO, this model allows for histological misdiagnosis of specimens.30,34–36
Several studies have recently demonstrated that there is substantial variability in the diagnosis of BO histology.22–24
Also, the model features utility estimates derived from actual subjects with BO who are at risk of cancer, which were used for the sensitivity analyses. This is superior to previous models which rely on consensus of experts in the field for some estimates. It is well demonstrated that physician estimates of quality of life and preferences for survival in diminished states often correlate poorly with patient preferences.37–40
Finally, the model does not assume a linear progression through states of dysplasia to cancer. Subjects may progress from no dysplasia to cancer, or may in fact regress to lesser states of dysplasia, as is seen in real world situations.
Important limitations of this model should also be recognised. Several of the estimates used to construct the model were based on relatively short term data. This is especially true of the outcomes of PDT, for which only relatively short term data are available. Extrapolating these data to longer horizons may introduce inaccuracies in the model. Also, there is variability in the reported rates of multiple variables in the model. While we have attempted to assess the effects of this variability on the model by means of sensitivity analysis, the possibility remains that if multiple estimates are extremely inaccurate, the model results may be inaccurate. Next, our model concentrates on Caucasian males, the group most likely to develop adenocarcinoma of the oesophagus. Whether the results are generalisable to other patient populations is unclear. Also, our utilities were in part based on assessments from US veterans with BO, using a visual analogue scale. The applicability of these utilities to other populations is unclear. Finally, the model assumes that the natural history of any given lesion will be the same regardless of previous treatment. For instance, those with HGD are assumed to have the same yearly risk of cancer whether they were assigned directly to the endoscopic surveillance arm or whether they initially underwent unsuccessful PDT and were then placed in the surveillance arm for their HGD after PDT failed. While this assumption is pragmatically essential to create the model, the accuracy of this assumption is not clear.
Perhaps the least well understood parameter in this study is the rate at which HGD progresses to cancer. Some studies have reported that one half or more of those patients undergoing oesophagectomy for HGD will subsequently be found to have carcinoma on the resection specimen.15
It is important to note that such surgical studies actually incorporate two sources of potential initial underdiagnosis of cancer—there is a sampling error inherent in random biopsies as well as a possibility of true progression of the lesion to cancer in the time between endoscopy and resection. In our model, we divided out the high risk of subsequent cancer in HGD using two variables. Firstly, we allowed for a generous sampling error rate, permitting as many as 20% of true cancers to be “missed” at random biopsies and therefore classified as lesser forms of dysplasia. Secondly, we also modelled true progression of the lesion. While our baseline rate of cancer progression was 2.5%, in sensitivity analyses we allowed that rate to range as high as 30% per cycle. Of note, we used data from a medical series8
showing a lower rate of progression from HGD to cancer than most of the surgical resection series. We chose to model these data in our base case because they represented the longest term data available on the largest cohort of HGD assembled, and because the investigators were compulsive about excluding prevalent cancers in their analysis.
A recent model assessing the potential effects of chemoprevention in BO with HGD arrived at similar conclusions to the present study.36
The authors found that chemoprevention with non-steroidal anti-inflammatory drugs for BO with HGD would likely be highly cost effective, if we assume that the preventative effects for cancer seen in epidemiological studies of non-steroidal anti-inflammatory drug users would be transmitted to those with BO. They concluded that any manoeuvre that would result in reduction of cancer occurrence in a group of high risk patients would likely be superior to a strategy that relies on early detection of developing cancers. The same phenomenon is noted in our study, whereby patients receiving ablative therapy achieved an improved life expectancy at a modest cost increase when compared with endoscopic surveillance. The take home message is that interventions that can potentially decrease cancer incidence, even if expensive, will be likely be cost effective compared with strategies that rely on decreasing mortality from treatment of cancer that has already developed.
In summary, our model suggests that endoscopic ablative therapy provides the longest quality adjusted life expectancy in subjects with BO and HGD. Endoscopic surveillance has a lower cost than endoscopic ablation but a condition of extended dominance exists such that endoscopic ablation will likely be the therapy of choice for most payers. Surgery is dominated by endoscopic surveillance in the base case model, and only becomes the favoured strategy at extremely high rates of progression from HGD to cancer.