Oesophageal cancer usually arises in the lining of the gullet. Photodynamic therapy involves two stages: a medicine that has an affinity for cancerous cells and is sensitive to a particular type of light is administered; an appropriate light source (often a laser) is then inserted into the gullet to activate the photosensitive medicine, which destroys the cancer cells.

The National Institute for Health and Clinical Excellence is examining photodynamic therapy for early-stage oesophageal cancer 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 early-stage oeshophageal cancer.

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 recommendations
  
• 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• The Advisory Committee will then prepare draft guidance which will be the basis for the Institute's guidance on the use of the procedure in the NHS in England, Wales and Scotland.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 Interventional Procedures Programme manual, which is available from the Institute's website (www.nice.org.uk/ipprogrammemanual).

Closing date for comments: 22 August 2006
Target date for publication of guidance: December 2006

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

Current evidence on the safety of photodynamic therapy (PDT) for early-stage oesophageal cancer appears adequate. PDT appears efficacious in reducing tumour bulk in carefully selected patients with small early-stage tumours. However, the current evidence is of poor quality and relates only to short-term outcomes; it is therefore not adequate to support the use of this procedure without special arrangements for consent, audit and clinical governance.

Clinicians wishing to undertake PDT for early-stage oesophageal cancer should take the following actions.

• Inform the clinical governance leads in their Trusts.
• Ensure that patients understand the uncertainty about the procedure's efficacy and provide them with clear written information. Use of the Institute's information for patients ('Understanding NICE guidance') is recommended (available from www.nice.org.uk/IPGXXXpublicinfo).
• Audit and review clinical outcomes of all patients having PDT for early-stage oesophageal cancer (see section 3.1).

Oesophageal cancer is a common cancer that is increasing in incidence. The most common histological types are squamous cell carcinoma and adenocarcinoma. Oesophageal cancer may cause difficulty in swallowing (dysphagia), weight loss, hoarseness, chronic cough and chest pain. The depth of penetration of the tumour determines the tumour stage; tumours that are superficial or have only penetrated the submucosa are defined as early-stage cancer. The treatment objective in early-stage oesophageal cancer is cure.

PDT involves the administration of a photosensitising agent by intravenous injection. The photosensitising agent is then activated by exposing the tumour to light, usually with a low-power laser introduced through an endoscope. The agent absorbs energy from the light (a photochemical effect), forming high-energy oxygen molecules that dest roy tumour cells. A number of different photosensitising agents have been used in PDT for oesophageal cancer. Treatment can be performed on an outpatient basis and is usually done under intravenous sedation.

Some studies reported results for PDT as monotherapy and some for PDT in combination with other treatment modalities, making comparison of outcomes difficult.

The definition of complete response or remission varied between the studies, but it was most commonly defined as no evidence of tumour on endoscopy, together with negative biopsy findings. Across case series, complete response was achieved in 37% (23/62), 75% (18/24), 81% (43/53), 97% (32/33) and 100% (18/18) of patients. However, the follow-up time varied between studies, and some patients received repeat PDT sessions. Where reported separately for subgroups, the response rate was 67% (22/33) for stage T1a tumours and 91% (20/22) for in situ squamous cell carcinomas.

In one case series, 5-year disease-specific survival was 72% in 56 patients treated with PDT monotherapy. In a case series of 38 patients, nine of whom received repeat PDT sessions, mean disease-free survival was 32 months. In another case series, 54% (13/24) of patients were alive without recurrence at a mean follow-up of 21 months. In a case series of 18 patients treated with PDT, mean overall survival was 60.5 months. Finally, in another case series of 21 patients, the mean local-progression-free survival period was 60 months. For more details, refer to the sources of evidence (see appendix).

The Specialist Advisers were divided in their opinions as to whether this procedure is established practice or novel and of uncertain safety and efficacy.

Oesophageal stenosis or stricture following PDT occurred in 7% (3/41), 8% (2/24), 11% (2/18), 13% (5/38), 25% (6/24) and 35% (43/123) of patients, although the photosensitising agent and type of light source used varied between studies. In one case series, chronic stenosis was reported to have occurred in 4% (5/123) of patients.

Two case series each reported development of oesophagotracheal fistula following PDT in 8% of patients (2/24 and 3/38).

The most commonly reported complication reported in relation to PDT for early oesophageal cancer was skin photosensitivity, which was reported in 0% (0/24), 8% (5/62) and 13% (16/123) of patients. Where specifically reported, second-degree sunburn occurred in 3% (1/38), 5% (5/102) and 13% (3/24) of patients. However, the timing of adverse events resulting from skin photosensitivity following administration of the photosensitiser was not always recorded. For more details, refer to the sources of evidence (see appendix).

The Specialist Advisers stated that adverse events may include death, photosensitivity, strictures, acute neuropathy, chest pain, low-grade fever, oesophageal or lung perforation, nausea, atrial fibrillation, congestive heart failure, skin reaction, recurrence/progression of cancer, pleural effusion, hypotension, pneumonia, oesophagitis and haemorrhage.

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 early-stage oesophageal cancer', May 2006.
  

Available from: www.nice.org.uk/ip339overview