Photodynamic therapy for Barrett's oesophagus - interventional procedures consultation document

NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE

Interventional procedure consultation document

Photodynamic therapy for Barrett's oesophagus

Barrett’s oesophagus is a condition in which the internal lining of the gullet (oesophagus) becomes damaged by long-term leaking of the stomach contents back into the gullet, known as ‘reflux’. Some patients with Barrett’s oesophagus may go on to develop cancer of the oesophagus. In photodynamic therapy, the patient is injected with a drug that makes the affected lining of the oeosophagus sensitive to light. Some hours after this a laser light source is passed down into the oesophagus where it is used to start a reaction that destroys the abnormal lining of the oesophagus, with the aim of preventing the progression to cancer.

The National Institute for Health and Clinical Excellence (NICE) is examining photodynamic therapy for Barrett's oesophagus and will publish guidance on its safety and efficacy to the NHS in England, Wales, Scotland and Northern Ireland. NICE’s Interventional Procedures Advisory Committee has considered the available evidence and the views of Specialist Advisers, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about photodynamic therapy for 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 provisional recommendations
  • the identification of factual inaccuracies
  • additional relevant evidence, with bibliographic references where possible.

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

The process that NICE 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  • The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.

For further details, see the Interventional Procedures Programme manual, which is available from the NICE website (www.nice.org.uk/ipprogrammemanual).

NICE is committed to promoting through its guidance race and disability equality and equality between men and women, and to eliminating all forms of discrimination. One of the ways we do this is by trying to involve as wide a range of people and interest groups as possible in the development of our guidance on interventional procedures. In particular, we aim to encourage people and organisations from groups in the population who might not normally comment on our guidance to do so. We also ask consultees to highlight any ways in which draft guidance fails to promote equality or tackle discrimination and give suggestions for how it might be improved. NICE reserves the right to summarise and edit comments received during consultations, or not to publish them at all, where in the reasonable opinion of NICE, the comments are voluminous, publication would be unlawful or publication would otherwise be inappropriate.

Closing date for comments: 23 March 2010

Target date for publication of guidance: June 2010

 

1       Provisional recommendations

1.1  Current evidence on the efficacy of photodynamic therapy (PDT) in patients with Barrett’s oesophagus with high-grade dysplasia (HGD) is adequate, provided that patients are followed up in the long term thereafter. There are no major safety concerns, although there is a risk of oesophageal stricture, and photosensitivity reactions are common. This procedure may be used in patients with Barrett’s oesophagus with HGD provided that normal arrangements are in place for clinical governance, consent and audit.

1.2  Current evidence on the efficacy and safety of PDT in patients with Barrett’s oesophagus with either low-grade dysplasia (LGD) or no dysplasia is inadequate in quality and quantity, and the balance of risks and benefits is not clear. Therefore, in these patients, the procedure should be used only with special arrangements for clinical governance, consent and audit or research.

1.3  Clinicians wishing to undertake PDT in patients with Barrett’s oesophagus with either LGD or no dysplasia should take the following actions.

·     Inform the clinical governance leads in their Trusts.

·     Ensure that patients and their carers understand the uncertainty about the procedure’s safety and efficacy and provide them with clear written information. In addition, the use of NICE’s information for patients (‘Understanding NICE guidance’) is recommended (available from www.nice.org.uk/guidance/IPGXXX/publicinfo). [[details to be completed at publication]]

·     Audit and review clinical outcomes of patients with Barrett’s oesophagus other than HGD having PDT (see section 3.1).

1.4  Patient selection for PDT in patients with Barrett’s oesophagus should be done by a multidisciplinary team experienced in the management of the condition.

1.5  PDT for Barrett’s oesophagus should only be carried out by endoscopists with specific training in this procedure.

2       The procedure

2.1    Indications and current treatments

2.1.1  Barrett’s oesophagus is a condition characterised by abnormal epithelium of the oesophagus and is associated with gastro-oesophageal reflux disease. In some patients, Barrett’s oesophagus may progress, through metaplasia and dysplasia, to neoplasia (oesophageal adenocarcinoma).

2.1.2  Cancer risk is higher for Barrett’s oesophagus patients with HGD (some of whom may already have developed early-stage cancer) than for those with LGD or no dysplasia. Patients with HGD are usually offered oesophagectomy, or frequent endoscopic surveillance and re-biopsy (with the aim of detecting neoplastic changes early) followed by oesophagectomy. Endoscopic treatments aiming to remove or ablate abnormal epithelium include endoscopic mucosal resection, argon plasma coagulation (APC), radiofrequency ablation, laser ablation, cryotherapy and multipolar electrocoagulation.

2.1.3  Patients with LGD or no dysplasia are usually offered regular endoscopic surveillance.

2.2    Outline of the procedure

2.2.1  PDT is usually carried out in an outpatient setting with the patient under intravenous sedation. A photosensitising agent is injected intravenously and is activated by illuminating the selected area with a laser inserted into the oesophagus. The photosensitising agent absorbs the light and forms high-energy oxygen molecules that cause necrosis of the Barrett’s epithelium through a photochemical effect. 

2.2.2  For extensive Barrett’s oesophagus, more than one treatment session may be required.

2.2.3  Patients are advised to avoid exposure to bright light and direct sunlight for several weeks after the procedure to minimise risk of photosensitivity reactions.

Sections 2.3 and 2.4 describe efficacy and safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the overview, available at www.nice.org.uk/IP232aoverview.

 

2.3    Efficacy

2.3.1  A randomised controlled trial (RCT) of 208 patients with HGD treated by PDT and omeprazole or omeprazole alone reported absence of HGD in 75% (104/138) and 36% (25/70) of patients respectively at 18-month follow-up (p < 0.0001). At 5-year follow-up, 48% and 4% of patients respectively still had no HGD (p < 0.0001).

2.3.2  An RCT of 72 patients without dysplasia treated by PDT or APC reported complete response (defined as reversal of columnar to squamous epithelium) in 50% (17/34) and 97% (33/34) of patients respectively at 12-month follow-up (p < 0.0001).

2.3.3  An RCT of 36 patients with LGD treated by PDT or a placebo reported biopsy-confirmed regression at 59–61 month follow-up in 89% (16/18) and 11% (2/18) of patients respectively (p < 0.001).

2.3.4  The RCT of 208 patients treated by PDT and omeprazole or omeprazole alone reported adenocarcinoma development in 15% (21/138) and 29% (20/70) of patients respectively during 5-year follow-up.

2.3.5  The Specialist Advisers listed key efficacy outcomes as reversal of dysplasia, prevention of dysplasia progression to adenocarcinoma and reversal of metaplasia.

2.4    Safety

2.4.1  One patient died 3 days after PDT treatment, with transmural oesophageal necrosis without perforation, in an RCT of 40 patients (13 with single-dose PDT vs 13 with two-dose PDT vs 14 with APC). 

2.4.2  Oesophageal stricture was reported in 36% (49/138), 3% (1/34), 33% (20/60), 15% (2/13), and 27% (35/131) of patients treated by PDT in the RCTs of 208, 72, 60, 26 and a non-randomised controlled trial of 199 patients respectively. Most were treated successfully with dilatation but 2 patients suffered perforation, requiring oesophagectomy.

2.4.3  Dysphagia was reported in 19% (absolute figure not stated) of patients treated by PDT in the RCT of 208 patients (timing of events not stated).

2.4.4  Photosensitivity reactions within 90 days of treatment were reported in 69% of patients in the PDT arm of the RCT of 208 patients (absolute figures not stated). Photosensitivity reactions occurred in 15% (5/34) and 15% (2/13) of patients in RCTs of 72 and 26 patients respectively, and in 60% (77/129) of patients in the non-randomised controlled trial of 199 patients. 

2.4.5  In the RCT of 72 patients treated by PDT or APC, buried glands were reported in 24% (4/17) and 21% (7/33) of patients respectively (difference reported as ‘non-significant’).

2.4.6  The Specialist Advisers listed anecdotal adverse events as pain and inflammation, ulceration and severe hypotension after the use of PDT with 5-aminolevulinic acid. They considered theoretical adverse events to include decompensation in patients with cirrhosis of the liver, and skin and retinal damage due to photosensitisation.

3     Further information

3.1  This guidance requires that clinicians undertaking the procedure make special arrangements for audit. NICE has identified relevant audit criteria and is developing an audit tool (which is for use at local discretion), which will be available when the guidance is published.

3.2  This procedure is a review of IPG82 published in 2004.

3.3  For related NICE guidance see www.nice.org.uk

Bruce Campbell
Chairman, Interventional Procedures Advisory Committee
February 2010

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This page was last updated: 19 August 2015