This advice report was commissioned by the Program in Evidence-Based Care (PEBC). A member of the Gastrointestinal Cancer Disease Site Group (DSG) agreed to serve as the clinical lead on this topic as it was not formally part of the Gastrointestinal Cancer DSG's guideline portfolio. This advice report is a convenient and up-to-date source of the best available evidence on the role porfimer sodium in the ablation of high-grade dysplasia associated with Barrett's esophagus, developed through a systematic review of the available evidence.
The early treatment of Barrett's esophagus with photodynamic therapy (PDT) in an attempt to prevent the possible later development of adenocarcinoma is clinically compelling. Presently, the best evidence in favour of PDT with porfimer sodium for these patients is the randomized controlled trial (RCT), which showed superiority for PDT treatment over treatment with omeprazole alone for both complete ablation of high-grade dysplasia (HGD) associated with Barrett's esophagus and the later development of adenocarcinoma. However, a randomized controlled trial comparison between surgery alone and PDT with porfimer sodium for these patients has yet to be published. The remaining data are currently limited to two case-series studies, and both report high-grade dysplasia ablation rates lower than 60% with a single course of treatment. In one of the trials PDT alone only ablated the dysplasia in eight of 73 patients (11%), while the remaining 35 patients required the additional treatment of neodymium-doped Yttrium Aluminum Garnet (Nd:YAG) laser to ablate the high-grade dysplasia. Also, the adverse effects observed with PDT using porfimer sodium are significant (e.g. stricture formation, light sensitivity) and are potentially fatal (e.g. esophageal perforation). The development of dysphagia secondary to stricture formation following PDT cannot be ignored. It is also possible that following PDT ablation, normal squamous tissue may grow over any remaining Barrett's tissue, which could possibly develop into an adenocarcinoma, while remaining hidden to endoscopic inspection for malignant conversion. Considering this, the role of PDT with porfimer sodium in the ablation of high-grade dysplasia associated with Barrett's esophagus remains unclear, especially as it's efficacy in comparison to the standard treatment of surgery is unknown.
Despite this, PDT provides some benefits over surgery alone. In the studies reviewed, PDT with porfimer sodium has a post-treatment mortality rate approaching zero, while surgical interventions report post-treatment mortality rates ranging from 6% to 14%, however, newer studies report that post-operative mortality with surgery alone also approaches zero. One benefit with PDT using porfimer sodium is that treatment may be given in multiple courses with minimal time between cycles (see Appendix 1 in the original guideline document).
It is recommended that for patients who are not candidates for surgery, either due to contraindications or patient preference, in the primary treatment of high-grade dysplasia associated with Barrett's esophagus, PDT with porfimer sodium could be considered.