COST-effectiveness, difficulty of diagnosis and short duration of current follow-up data are the main reasons why surveillance with endoscopy, rather than radiofrequency ablation, is still considered the gold standard treatment for Barrett oesophagus with low-grade dysplasia, according to upper gastrointestinal experts.
Dr Tim Bright, senior lecturer in surgery and a consultant at the Oesophago-Gastric Surgery Unit at Flinders Medical Centre, told MJA InSight that treatment with radiofrequency ablation — the direct application of radiofrequency energy to the oesophageal mucosa using special balloons or catheters — had limited applicability in Australia as it was not funded.
Dr Bright said even in the best centres in Australia using ablation the recurrence rate was about 20%, “so we would still have to do all the surveillance endoscopies that we would do with low-grade dysplasia (LGD) anyway”.
He was commenting on a randomised trial, published in JAMA, of ablation versus endoscopic surveillance in patients with Barrett oesophagus and a confirmed diagnosis of LGD, which found ablation reduced the risk of progression to high-grade dysplasia or adenocarcinoma from 26.5% to 1.5%. (1)
The study, which included 136 patients who were followed up for 3 years, also showed that ablation reduced the risk of progression to adenocarcinoma from 8.8% to 1.5%, an absolute risk reduction of 7.4%.
Two pathologists had to agree on the diagnosis of LGD in the study participants, with a third pathologist assessment required if there was disagreement. This resulted in a very tight definition of LGD and about three-quarters of patients originally considered for the trial were excluded (375/511).
Almost 20% of ablation patients experienced a treatment-related adverse event, the most common being stricture. The trial was terminated early due to the superiority of the primary end point, and concerns about patient safety if it continued.
A large percentage of patients (28%) had regression of their lesion in the follow-up period.
An accompanying editorial warned that because the study used a very tight definition of LGD, “85% of patients diagnosed with LGD would not be eligible for this procedure”. The editorial said finding biological, molecular and histological markers to identify candidates for ablation should be a research priority. (2)
Professor David Watson, head of the department of surgery at Flinders University, told MJA InSight that LGD meant different things to different people.
“The pathologists don’t agree. There is poor intraobserver agreement with diagnosis of LGD in the community.”
Professor Watson said cost-effectiveness was a big obstacle for ablation, citing a Medical Services Advisory Committee report from 2010 that found an “incremental cost-effectiveness ratio” for ablation compared with surveillance of $78 975 per quality-adjusted life-year (QALY). (3)
“The threshold for cost-effectiveness [in terms of recommending funding] is usually about $50 000 per QALY”, he said.
Dr Bright said he was concerned that the JAMA study did not have a long enough period of follow-up to accurately assess the value of ablation for LGD.
“As a surgeon I’m naturally biased to oesophagectomy but it’s a bloody horrible thing to do to someone and if it can be avoided then I’m all in favour”, he said. “But in the case of [ablation] for LGD, there’s nowhere near the length of follow-up been done. My question is what do I do for the guy who’s 40 and may require another 40 years of surveillance?
“If we were able to predict no recurrence with [ablation] and that therefore no surveillance was necessary then we’d be very enthusiastic about it, but there is no predictive model available yet.”
Dr Brad Kendall, a senior staff gastroenterologist at Princess Alexandra Hospital, Brisbane said the study showed ablation had “a lot of potential for how we manage patients” but was not yet ready for widespread clinical use in the management of patients with Barrett LGD in Australia.
“The key is the diagnosis of LGD must be confirmed by an expert gastrointestinal pathologist”, he told MJA InSight. “In this group of high-risk patients with confirmed LGD the use of [ablation] showed an absolute risk reduction of progression to high-grade dysplasia or adenocarcinoma of 25% over 3 years.
“It’s a very well conducted European multicentre study in expert centres, and it needs replicating elsewhere in the world, but the results show a lot of promise.”
Cancer Council Australia is working to develop new guidelines for the diagnosis and management of Barrett oesophagus. Ms Christine Vuletich, manager of the Council’s Clinical Guidelines Network, said the draft guidelines would be publicly released in May.