Interventional procedure consultation document

Electrochemotherapy for primary basal cell carcinoma and primary squamous cell carcinoma

Treating basal cell carcinoma and squamous cell carcinoma using pulses of electricity together with chemotherapy

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common types of skin cancer. They are generally slow-growing but can cause extensive tissue destruction if not treated, and SCC can spread to other parts of the body.

In electrochemotherapy an anticancer drug is given by injection either into a vein or directly into a tumour. Short, powerful pulses of electricity are then applied to the tumour. The electrical energy opens the membranes (outer coverings) of the tumour cells, allowing the anticancer drug to pass through into the cells and have a more damaging effect.

The National Institute for Health and Care Excellence (NICE) is examining electrochemotherapy for primary basal cell carcinoma and primary squamous cell carcinoma 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 electrochemotherapy for primary basal cell carcinoma and primary squamous cell carcinoma.

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·       The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.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

Through its guidance NICE is committed to promoting race and disability equality, 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 interventional procedures guidance. In particular, we aim to encourage people and organisations from groups who might not normally comment on our guidance to do so.

In order to help us promote equality through our guidance, we should be grateful if you would consider the following question:

Are there any issues that require special attention in light of NICE’s duties to have due regard to the need to eliminate unlawful discrimination, advance equality of opportunity, and foster good relations between people with a characteristic protected by the equalities legislation and others?

Please note that 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: 20 September 2013

Target date for publication of guidance: January 2014

 

 

 

1                      Provisional recommendations

 

1.1                  Current evidence on the safety of electrochemotherapy for primary basal cell carcinoma (BCC) and primary squamous cell carcinoma (SCC) raises no major concerns. Evidence on its efficacy is limited in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, local audit and with submission of data to a register (see 1.5). Patient selection is particularly important.

 

1.2                  Clinicians wishing to undertake electrochemotherapy for treating primary BCC and primary SCC should take the following actions.

·      Inform the clinical governance leads in their NHS trusts.

·      Ensure that patients understand the uncertainty about the procedure’s efficacy and why it is being offered as an alternative to other established methods of treatment, and provide them with clear written information. In addition, the use of NICE’s information for the public [[URL to be added at publication]] is recommended.

 

1.3                  Patient selection should be carried out by a specialist skin cancer multidisciplinary team. Careful consideration should be given to the reasons for offering electrochemotherapy, especially in the context of treating primary BCC and SCC with curative intent.

 

1.4                  This procedure should only be carried out by a clinician with specific training in the technique.

 

1.5                  Clinicians should submit data on all patients undergoing electrochemotherapy (including details of case selection, methods of follow-up and outcomes) to the InspECT register, an international register dedicated to electrochemotherapy, and review clinical outcomes locally. Entry into research trials should also be considered, with a view to providing data about cure and about recurrence rates, compared with other forms of treatment.

 

2                      Indications and current treatments

 

2.1                  Basal cell carcinoma (BCC) is the most common type of skin cancer in the UK. It is generally a slow-growing, locally invasive epidermal skin tumour that rarely spreads to other parts of the body. Although it is not usually life-threatening, the tumour can cause extensive tissue destruction if it is not treated. Squamous cell carcinoma (SCC) is the second most common type of skin cancer in the UK. It may spread into local lymph nodes and metastasise to other parts of the body.

 

2.2                  Current treatments for BCC and SCC include surgical excision and radiotherapy, and less commonly curettage, cryotherapy and chemotherapy.

 

3                      The procedure

 

3.1                  Electrochemotherapy is a local treatment that aims to enhance the effects of chemotherapy and can be performed as an outpatient procedure.

 

3.2                  The procedure is performed with the patient under general or local anaesthesia with or without sedation. Chemotherapy drugs are given first, either intravenously or directly into the tumour. Drug dose is individualised based on either body surface area or tumour volume. Shortly after drug administration, brief and intense electric pulses are delivered around or directly into the tumour using either surface plates or needle electrodes. This makes the cell membranes more permeable to the chemotherapy drugs so that their cytotoxic effect is increased. Different-shaped plates or electrodes are used depending on the tumour size, extent, shape and location. Treatment duration may vary depending on the number and size of tumours. Larger tumours may need several applications to cover the entire surface. Repeated treatments can be performed if necessary (within the lifetime dose limits of the chemotherapy drugs).

 

4                      Efficacy

 

This section describes efficacy 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.

4.1                  A non-randomised comparative study of 113 patients (85 basal cell carcinoma [BCC] and 28 squamous cell carcinoma [SCC]) compared 2 different electric pulse sequences for electrochemotherapy of stage I (T1N0M0) BCC and SCC tumours. The complete response rate was 100% initially (not otherwise defined) and 83% at 12 months.

 

4.2                  A non-randomised comparative study of 34 patients comparing electrochemotherapy with intratumoural bleomycin or electric pulse therapy included 21 patients with BCC or SCC (66 tumours). The study reported an objective response rate of 100% and a complete response of 94% (51/54) in BCC primary tumours treated with electrochemotherapy at 12 weeks. The 1 SCC tumour treated with electrochemotherapy had a partial response. There were no complete responses in the 11 BCC tumours treated with either intratumoural bleomycin alone (8 tumours) or electric pulse therapy alone (3 tumours).

 

4.3                  The study of 113 patients (85 BCC and 28 SCC tumours) with an initial 100% complete response reported that 14% (16/113) of tumours recurred between 2 and 6 months after treatment (no further details reported).

 

4.4                  A case series of 6 patients (3 BCC and 3 SCC tumours) reported no damage to nerve or ocular function after electrochemotherapy in 4 patients with tumours close to the facial nerve or eye muscles.

 

4.5                  The case series of 6 patients (3 BCC and 3 SCC tumours) reported a ‘very satisfactory’ cosmetic outcome at between 6 and 12 months after electrochemotherapy (no further details reported).

 

4.6                  The specialist advisers listed additional key efficacy outcomes as quality of life, control of bleeding and reduction of odour from fungating tumours.

 

5                      Safety

This section describes 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.

 

5.1                  Localised involuntary muscle contractions and a sensation of a jolt or shock associated with the electric pulses were reported in the study of 34 patients and 3 case series of 50, 24 and 15 patients. They stopped immediately when the electric pulses were discontinued.

 

5.2                  A septal cartilage perforation was reported in 1 patient receiving treatment in the right nasal vestibule in the case series of 6 patients. This occurred after a biopsy performed 8 weeks after treatment. No further details were reported.

 

5.3                  Slight burning of the skin was reported in 87% (7/8) of patients on whom the plate electrodes were used in the study of 34 patients. This healed within 6–8 weeks. No further details were reported.

 

5.4                  Erythema and oedema 72 hours after treatment were reported in the case series of 24 patients. No further details were reported.

 

5.5                  Superficial leukonecrosis in large tumours in which the skin was altered before electrochemotherapy was reported in the case series of 50 patients. No further details were reported.

 

5.6                  Increased tear production was reported in 2 patients who received treatment in the medial canthus in the case series of 6 patients. This caused no visual impairment and resolved within 2 months. No further details were reported.

 

5.7                  Post-treatment pain was described as ‘moderate’ and was managed with paracetamol and diclofenac for 5–7 days in the case series of 6 patients.

 

5.8                  Other side effects attributed to the chemotherapy agent such as slight nausea and allergic reactions were also reported.

 

5.9                  The specialist advisers listed additional key safety outcomes as increase in wound exudate after the procedure and chemotherapy toxicity, specifically pulmonary fibrosis.

 

6                      Committee comments

 

6.1                  The Committee was advised that there are well-established methods for treating basal and squamous cell cancers of the skin with curative intent. It noted that this procedure may be useful in managing inaccessible or otherwise difficult-to-treat primary basal cell carcinomas and squamous cell carcinomas in carefully selected patients.

 

6.2                  The Committee noted that patients may experience pain and ulceration after treatment.

 

7                      Further information

 

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

 

_{Personal data will not be posted on the NICE website. In accordance with the Data Protection Act names will be anonymised, other than in circumstances where explicit permission has been given.}

 _{It is the responsibility of consultees to accurately cite academic work in order that they can be validated.}

 

Bruce Campbell

Chairman, Interventional Procedures Advisory Committee

August 2013