Interventional procedure consultation document

Irreversible electroporation for treating renal cancer

Treating renal cancer using high energy pulses of electricity

Renal cancer is cancer of the kidney. Irreversible electroporation is a process that uses high energy electrical pulses to kill cancer cells. It is applied directly to the tumour through special needles. The main difference between this procedure and some other techniques for destroying tumours is that it does not produce extreme heat or cold. This means that it may cause less damage to healthy surrounding tissues than some other procedures.

The National Institute for Health and Clinical Excellence (NICE) is examining irreversible electroporation for the treatment of renal cancer 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 irreversible electroporation for the treatment of renal 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 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• The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.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).

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 and promote equality 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 November 2012

Target date for publication of guidance: 27 February 2013

1   Provisional recommendations

1.1   Current evidence on the safety and efficacy of irreversible electroporation for the treatment of renal cancer is inadequate in quantity and quality, and there are recognised risks. Therefore, this procedure should only be used in the context of research. In particular, studies should report the effect of the procedure on local tumour control and patient survival.

2   The procedure

2.1   Indications and current treatments

2.1.1   The most common type of renal cancer in adults is renal cell carcinoma. Symptoms and signs may include pain and haematuria. Some patients are diagnosed on imaging studies during investigation for other disorders. Patients with certain genetic syndromes that predispose them to kidney tumours may be diagnosed during routine imaging surveillance. Establishing the diagnosis and assessing the prognosis of some renal tumours can be difficult and not all are actively treated.

2.1.2   Treatment options include laparoscopic (or open) partial or total nephrectomy, and ablation techniques including radiofrequency ablation and cryoablation. Drug therapy is commonly used for advanced renal cancer. Irreversible electroporation is a non-thermal cell-destruction technique which may allow targeted destruction of cancerous cells with minimal damage to surrounding structures (such as major blood vessels and ducts).

2.2   Outline of the procedure

2.2.1   The aim of irreversible electroporation is to permanently damage cell membranes, leading to cell death. This is done by applying an intense electrical field using high-voltage direct current. This creates multiple holes in the cell membrane and damages the cell’s homeostasis mechanisms.

2.2.2   The procedure is performed with the patient under general anaesthesia. A neuromuscular blocking agent is essential to prevent uncontrolled severe muscle contractions caused by the electric current. Bipolar or unipolar electrode needles are introduced percutaneously (or by open surgical or laparoscopic approaches) and guided into place in and adjacent to the target tumour under imaging guidance. A series of very short electrical field pulses are delivered over several minutes to ablate the tumour. The electrodes may be repositioned to extend the zone of electroporation until the entire tumour and an appropriate margin have been ablated. Cardiac synchronisation is used to time delivery of the electrical pulse within the refractory period of the heart cycle, minimising the risk of arrhythmia.

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/guidance/IP/1021/overview

2.3   Efficacy

2.3.1   A case series of 38 patients including 7 patients with renal cancer (10 tumours) reported a complete response in 5 tumours and progressive disease in 5 tumours at 3-month follow-up, assessed by modified ‘Response evaluation criteria in solid tumors’ (RECIST). Computed tomography follow-up at 3 months confirmed ablation of the tumour in 5 of the 7 patients, although 2 patients needed a second irreversible electroporation procedure.

2.3.2   The Specialist Advisers listed key efficacy outcomes as local tumour control, time to progression, and patient survival.

2.4   Safety

2.4.1   Transient cardiac arrhythmia was reported in 6 patients in the case series of 38 patients (4 patients had ventricular tachycardia, 1 patient had supraventricular tachycardia and 1 patient had atrial fibrillation). Only 2 of these 6 patients had cardiac synchronisation. All of the arrhythmias resolved without treatment except for the atrial fibrillation in 1 patient, which was treated by cardioversion. Transient ventricular tachycardia was reported during 25% (7/28) of procedures in a case series of 21 patients with primary or metastatic cancer (liver, kidney or lung). Arterial blood pressure was ‘markedly decreased’ in 4 of the 7 procedures. The authors noted that a synchronisation device was used from early in the trial, but they had variable success with synchronisation. Intraoperative supraventricular extrasystole was reported in 1 patient in a case series of 6 patients. No electrocardiography (ECG)-related changes were detected after the procedure or at follow-up (after 12 weeks).

2.4.2   Partial ureteric obstruction and increasing creatinine level were reported in 1 patient with renal cancer in the case series of 38 patients (timing not reported). The patient’s ureter had been damaged previously by radiofrequency ablation. The obstruction was treated by inserting a ureteric stent.

2.4.3   Extreme increases in blood pressure during the procedure (up to 200/100 mmHg from a baseline of 140/60 mmHg) were reported in 7% (2/28) of procedures in the case series of 21 patients with tumours in the liver, kidney or lung (both patients were being treated for renal cancer). In 1 patient, the blood pressure increase lasted for more than a few minutes and medical treatment was needed. The position of the electrodes was subsequently checked and thought to be in the adrenal gland. Transient increases in systolic blood pressure of approximately 20 to 30 mmHg after treatment cycles were reported for all patients in the same study.

2.4.4   Contractions of the entire upper body (similar to those seen with a grand mal seizure) after each electrical pulse stimulation were reported in the case series of 21 patients, in patients who were inadequately paralysed (number of patients not reported).

2.4.5   The Specialist Advisers listed additional theoretical adverse effects as damage to surrounding organs, minor bleeding, sepsis and ureteric stricture.

2.5   Other comments

2.5.1   The Committee noted the claim that this procedure may cause less damage to surrounding structures (such as major blood vessels) than other types of ablative treatment for renal cancer, but it considered that more evidence is needed to support this.

3    Further information

3.1    For related NICE guidance see the NICE website.

Barrie White

Vice Chairman, Interventional Procedures Advisory Committee

October, 2012