The National Institute for Clinical Excellence is examining photodynamic therapy for high-grade dysplasia in Barrett's oesophagus and will publish guidance on its safety and efficacy to the NHS in England, Wales and Scotland. The Institute's Interventional Procedures Advisory Committee has considered the available evidence and the views of Specialist Advisors, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about photodynamic therapy for high-grade dysplasia in Barrett's oesophagus.

This document summarises the procedure and sets out the provisional recommendations made by the Advisory Committee. It has been prepared for public consultation. The Advisory Committee particularly welcomes:

• comments on the preliminary recommendation
• the identification of factual inaccuracies
• additional relevant evidence.

Note that this document is not the Institute's formal guidance on this procedure. The recommendations are provisional and may change after consultation.

The process that the Institute will follow after the consultation period ends is as follows:

• The Advisory Committee will meet again to consider the original evidence and its provisional recommendations in the light of the comments received during consultation.
• The Advisory Committee will then prepare draft guidance which will be the basis for the Institute's guidance on the use of the procedure in the NHS in England, Wales and Scotland.

For further details, see the Interim Guide to the Interventional Procedures Programme, which is available from the Institute's website (www.nice.org.uk/ip).

Closing date for comments: 25 May 2004

Target date for publication of guidance: August 2004

Note that this document is not the Institute's guidance on this procedure. The recommendations are provisional and may change after consultation.

Current evidence suggests that there are no major safety concerns and that photodynamic therapy is efficacious in downgrading dysplasia in Barrett's oesophagus, when used for treatment of high-grade dysplasia (a pre-malignant lesion). However the efficacy of photodynamic therapy for influencing the prognosis of Barrett's oesophagus is not clear.

Clinicians wishing to undertake photodynamic therapy for high-grade dysplasia in Barrett's oesophagus should take the following action.

• Inform the clinical governance leads in their Trusts.
• Inform patients, as part of the consent process, about the uncertainty of influencing their long-term prognosis and provide them with clear written information. Use of the Institute's Information for the Public is recommended.
• Audit and review clinical outcomes of all patients having photodynamic therapy for high-grade dysplasia in Barrett's oesophagus.

Publication of long-term efficacy outcomes will be useful in reducing the current uncertainty. The Institute may review the procedure upon publication of further evidence.

Barrett's oesophagus is a condition characterised by an abnormal lining of the oesophagus, which occurs in patients with a long history of gastro-oesophageal reflux disease.

In a minority of people, Barrett's oesophagus may progress through a number of increasingly severe series of stages (dysplasia) to cancer. High-grade dysplasia is the stage which immediately precedes the occurrence of cancer, but it is not possible to predict how soon cancer will develop. The grade of dysplasia and the amount of oesophagus affected are thought to be the most important risk factors for progression to cancer.

Oesophagectomy is the most radical treatment option for high-grade dysplasia, because removal of the whole oesophagus means that the risk of progression to cancer is removed. However, oesophagectomy is a major operation with the potential for morbidity and mortality. Less invasive treatments include laser ablation, endoscopic mucosal resection and photodynamic therapy. All of these procedures aim to ablate the specialised columnar epithelium which is affected by dysplasia and to promote the regeneration of normal squamous epithelium.

Photodynamic therapy involves the administration of a photosensitising agent by intravenous injection. The agent is then activated by the application of light to the selected area, usually with a low-power laser. It absorbs the energy from the light, resulting in the formation of high-energy oxygen molecules. These molecules interact with the tissue, leading to tumour necrosis by a photochemical rather than a thermal effect.

Treatment can be performed on an outpatient basis and is usually applied to approximately 7 cm of the affected oesophagus at a time to avoid toxicity. A second treatment session can be conducted if the affected area is greater than is greater than 7 cm.

The evidence on efficacy is based largely on three uncontrolled reports and one unpublished randomised trial. The results of all four reports showed that dysplasia was downgraded (from high-grade dysplasia to Barrett's oesophagus without dysplasia) in the majority of patients (77-98%) following the procedure. Elimination of Barrett's oesophagus was achieved in 42% (25/60) to 98% (47/48) of patients; however residual disease was often ablated by laser treatment. For more details, refer to the sources of evidence (see Appendix).

One study of 103 patients (80 with high-grade dysplasia) reported a survival rate of 78%. In an extended follow-up of 65 of these 80 patients, three (5%) developed carcinoma at a mean follow-up of 58 months. Initial results from the unpublished randomised controlled trial indicate that at 24 months, 14% (18/130) of patients treated with photodynamic therapy progressed to cancer compared with 28.6% (20/70) of patients receiving medication only. This study is still in progress and these are preliminary findings only. For more details, refer to the sources of evidence (see Appendix).

One Specialist Advisor stated that a proportion of patients undergoing photodynamic therapy would have undetected advanced carcinomas, which would be beyond the reach of the therapy.

Oesophageal strictures and cutaneous reactions associated with the photosensitiser were the most commonly reported complications following photodynamic therapy. Oesophageal strictures occurred in 23% (11/48) to 34% (34/100) of patients in the published studies. Skin reactions occurred in around a third of patients undergoing photodynamic therapy. These included mild, moderate and severe reactions, with 3% (3/100) to 15% (7/48) of patients experiencing severe photosensitivity reactions requiring medical treatment. For more details, refer to the sources of evidence (see Appendix).

Oesophageal perforation, pleural effusions and atrial fibrillation were also reported, with an incidence of around 3-4%. For more details, refer to the sources of evidence (see Appendix).

The Specialist Advisors listed the main adverse events as photosensitivity and development of strictures. One Advisor stated that underlying malignancy might continue to grow unobserved because of the superficial healing of the Barrett's oesophagus. One Advisor noted that pleural effusions and atrial fibrillation.as potential complications.

The current evidence is based on small patient numbers.

The following document, which summarises the evidence, was considered by the Interventional Procedures Advisory Committee when making its provisional recommendations.

• Interventional procedure overview of photodynamic therapy for high-grade dysplasia for Barrett's oesophagus, November 2003

Available from: www.nice.org.uk/ip232overview