Five-year efficacy and safety of photodynamic therapy with Photofrin in Barrett's high-grade dysplasia

Background: Barrett's esophagus (BE) with high-grade dysplasia (HGD) is a risk factor for development of esophageal carcinoma. Photodynamic therapy (PDT) with Photofrin (PHO) has been used to eliminate HGD in BE. Objective: Our purpose was to compare PHOPDT plus omeprazole with omeprazole only (OM). Design: Five-year follow-up of a randomized, multicenter, multinational, pathology-blinded HGD trial. Setting: 30 sites in 4 countries. Patients: 208. Interventions: Patients with BE and HGD were randomized (2:1) to PHOPDT (n = 138) or OM (n = 70) into a 2-year trial followed up for 3 more years. PHOPDT patients received 2 mg/kg PHO intravenously followed by endoscopic laser light exposure of Barrett's mucosa at a wavelength of 630 nm within 40 to 50 hours to a maximum of 3 courses at least 90 days apart. Both groups received 20 mg of OM twice daily. Pathologists at one center assessed biopsy specimens in a blinded fashion. Main Outcome Measurement: HGD ablation status over 5 years of follow-up. Results: At 5 years PHOPDT was significantly more effective than OM in eliminating HGD (77% [106/138] vs 39% [27/70], P < .0001). A secondary outcome measure preventing progression to cancer showed a significant difference (P = .027) with about half the likelihood of cancer occurring in PHOPDT (21/138 [15%]) compared with OM (20/70 [29%]), with a significantly (P = .004) longer time to progression to cancer favoring PHOPDT. Limitations: Not all patients were available for follow-up. Conclusions: This 5-year randomized trial of BE patients with HGD demonstrates that PHOPDT is a clinically and statistically effective therapy in producing long-term ablation of HGD and reducing the potential impact of cancer compared with OM.