Spotlight on esophageal adenocarcinoma

High-dose proton-pump inhibitors and aspirin appeared effective for chemoprevention in patients with Barrett's esophagus in one study, while another study found a positive association between human papillomavirus status and survival in patients with Barrett's high-grade dysplasia and esophageal adenocarcinoma.


One recent study tested therapies for esophageal adenocarcinoma prevention in patients with Barrett's esophagus, while another found a favorable relationship between positive human papillomavirus (HPV) status and survival in patients with Barrett's high-grade dysplasia and esophageal adenocarcinoma.

The first study, which received industry support, had a 2x2 factorial design and was conducted at 84 centers in the U.K. and one in Canada. Researchers randomized patients with Barrett's esophagus of 1 cm or more to receive high-dose (40 mg twice daily) or low-dose (20 mg once daily) esomeprazole proton-pump inhibitor (PPI) therapy, with or without aspirin (300 mg/d in the U.K., 325 mg/d in Canada), for at least eight years. The primary composite endpoint was time to all-cause mortality, esophageal adenocarcinoma, or high-grade dysplasia in the intention-to-treat population.

Results were published online on July 26 by The Lancet.

Overall, 2,557 patients were assigned to receive low-dose PPI and no aspirin (n=705), high-dose PPI and no aspirin (n=704), low-dose PPI and aspirin (n=571), or high-dose PPI and aspirin (n=577). Median follow-up and treatment duration was 8.9 years, during which 313 primary events occurred.

High-dose PPI (139 events in 1,270 patients) was superior to low-dose PPI (174 events in 1,265 patients; time ratio, 1.27 [95% CI, 1.01 to 1.58]; P=0.038). Aspirin was not significantly better than no aspirin unless patients using NSAIDs were censored at the time of first use (time ratio, 1.29 [95% CI, 1.01 to 1.66]; P=0.043; n=2,236).

High-dose PPI and aspirin had the strongest effect compared with low-dose PPI without aspirin (time ratio, 1.59; 95% CI, 1.14 to 2.23; P=0.0068). The numbers needed to treat to prevent one high-grade dysplasia, adenocarcinoma, or death were 34 for high-dose PPI (vs. low-dose PPI) and 43 for aspirin (vs. no aspirin). Treatment-related serious adverse events (e.g., hemorrhage) occurred in 61 participants.

The authors noted limitations of the trial, such as a lack of generalizability to nonwhite populations and the fact that participants were not blinded to drug treatment.

Further data are needed to confirm the positive combined effects of aspirin and PPI use before this approach should be recommended for chemoprevention, an accompanying comment noted. In addition, while the risk reduction and dose-response relationship for PPI are convincing, “Future guidelines should consider whether the notion of the lowest possible dose to control symptoms still applies and whether high-dose PPIs should be used as prophylaxis in Barrett's oesophagus,” the author wrote.

In the second study, researchers retrospectively examined survival rates of patients with Barrett's high-grade dysplasia and esophageal adenocarcinoma, with or without HPV infection. The main outcomes were disease-free survival and overall survival. Results were published online on Aug. 3 by JAMA Network Open.

Among 142 patients (mean age, 66.0 years; 88.7% male; 100% white), 37 had HPV-positive high-grade dysplasia or esophageal adenocarcinoma and 105 were HPV-negative. Mean disease-free survival was higher in the HPV-positive group than in the HPV-negative group (40.3 vs. 24.1 months; difference, 16.2 months [95% CI, 5.7 to 26.8 months; P=0.003]), as was overall survival (43.7 vs. 29.8 months; difference, 13.9 months [95% CI, 3.6 to 24.3 months]; P=0.009). In addition, recurrence or progression (P<0.001), distant metastasis (P=0.02), and death from esophageal adenocarcinoma (P=0.01) were all reduced in the HPV-positive cohort compared to the HPV-negative cohort.

The study's small sample size and retrospective design were limitations, and its case-control nature introduced selection bias and confounding (although HPV status was not known at enrollment or at the time of treatment decision), the authors noted.

Although this study highlights a potential role of HPV status in the prognosis of esophageal adenocarcinoma, “the use of HPV as a predictive marker for treatment remains unproven,” an accompanying commentary said. “While the results of this small cohort study are impressive, they are preliminary, and the study requires confirmation in a larger prospective trial,” the editorialist wrote.