2 The procedure
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 during investigation with imaging 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 is claimed to allow targeted destruction of cancerous cells with less damage to surrounding structures (such as major blood vessels and ducts).
2.2.1 The aim of irreversible electroporation is to destroy cancerous cells by subjecting them to a series of short electrical pulses using high-voltage direct current. This creates multiple holes in the cell membrane, irreversibly damaging the cell's homeostasis mechanisms and leading to cell death.
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 using imaging guidance. A series of very short electrical pulses is delivered over several minutes to ablate the tumour. The electrodes may then 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.
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' (modified 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.
2.4.1 The case series of 38 patients reported transient cardiac arrhythmia in 6 patients (4 patients had ventricular tachycardia, 1 patient had supraventricular tachycardia and 1 patient had atrial fibrillation). Two of these patients had cardiac synchronisation and 4 did not. All of the arrhythmias resolved without treatment except for the atrial fibrillation in 1 patient, which was treated by cardioversion.
2.4.2 A case series of 21 patients with primary or metastatic cancer (liver, kidney or lung) reported transient ventricular tachycardia during 25% (7/28) of procedures. In 4 of the 7 procedures, arterial blood pressure was 'markedly decreased' (not defined). 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-related changes were detected after the procedure or at follow-up (after 12 weeks).
2.4.3 The case series of 38 patients reported partial ureteric obstruction and increasing creatinine level in 1 patient with renal cancer (timing not reported). The patient's ureter had been damaged previously by radiofrequency ablation. The obstruction was treated by inserting a ureteric stent.
2.4.4 The case series of 21 patients with tumours in the liver, kidney or lung reported extreme increases in blood pressure during the procedure (up to 200/100 mmHg from a baseline of 140/60 mmHg) in 7% (2/28) of procedures (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.
2.4.5 The Specialist Advisers listed additional theoretical adverse effects as damage to surrounding organs, minor bleeding, sepsis and ureteric stricture.