Interventional procedure consultation document

Focal therapy using cryoablation for localised prostate cancer

Treating areas of prostate cancer using freezing (cryotherapy) needles

The prostate is a small gland near a man's bladder. Symptoms of localised prostate cancer include difficulties in passing urine, although the disease is often diagnosed before symptoms develop. Focal therapy using freezing (cryotherapy) needles aims to find and destroy only the cancerous part of the prostate, avoiding treatment of healthy tissue. Freezing needles are inserted into the tumour areas, which are then destroyed. The procedure aims to lower the risk of side effects that can occur when radical treatment is given to the whole of the prostate gland (such as loss of bladder control and sexual function).

The National Institute for Health and Clinical Excellence (NICE) is examining focal therapy using cryoablation for localised prostate 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 focal therapy using cryoablation for localised prostate 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• The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.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 December 2011

Target date for publication of guidance: March 2012  

1   Provisional recommendations

1.1   Current evidence on the safety of focal therapy using cryoablation for localised prostate cancer shows no major concerns. However, evidence on efficacy is limited in quantity and there is a concern that prostate cancer is commonly multifocal. Therefore this procedure should only be used with special arrangements for clinical governance, consent and audit or research.

1.2   Clinicians wishing to undertake focal therapy using cryoablation for localised prostate cancer 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 efficacy and the risks to sexual and urinary function, 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]]
• Clinicians should enter details about all patients undergoing focal therapy using cryoablation for localised prostate cancer onto the British Association of Urological Surgeons (BAUS) cancer register (www.baus.org.uk) and review clinical outcomes locally.

1.3   Patient selection and treatment should be carried out by a multidisciplinary urological cancer team.

1.4   NICE encourages further research into focal cryoablation for localised prostate cancer. This should take the form of controlled studies comparing the procedure against other forms of management. Studies should clearly define patient selection criteria and should report long-term outcomes.

2   The procedure

2.1   Indications and current treatments

2.1.1   Symptoms of localised prostate cancer include difficulty in passing urine, although the condition is often diagnosed at an asymptomatic stage.

2.1.2   Treatment options for patients with localised prostate cancer include active surveillance, radical prostatectomy, external beam radiotherapy, brachytherapy, and ablation of the whole gland using cryotherapy or high-intensity focused ultrasound (HIFU). All radical treatment options are associated with substantial risks of sexual, urinary or bowel dysfunction. Focal therapy using cryoablation is intended to be used in patients with localised prostate cancer – specifically patients with tumours that are confined to one prostatic lobe.

2.2   Outline of the procedure

2.2.1   Imaging and biopsy mapping studies are used to confirm that the tumour is suitable for focal therapy and to show its precise location. With the patient under local or general anaesthesia, the bladder is catheterised using a supra-pubic catheter. Using transrectal ultrasound and a template placed on the perineum, fine needles are inserted transperineally into the prostate. Pressurised argon is passed through the needles to freeze the targeted area of the prostate, destroying the tissue. Implantable temperature probes and transrectal ultrasound guidance are used to monitor the treatment, and steps are taken to protect surrounding tissue from the effects of freezing.

2.2.2   After treatment patients are usually followed up regularly with prostate-specific antigen (PSA) measurements and repeated biopsies to detect recurrence. 

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/968/overview

2.3   Efficacy

2.3.1   A case series of 54 patients reported overall and disease-specific survival of 100% among 48 patients followed up for a mean of 4.5 years. Two case series of 54 and 60 patients reported biochemical recurrence-free survival in 94% (45/48) and 80% (41/51) of patients followed up for a mean of 2 years and 15.2 months respectively. In a case series of 25 patients 36% (9/25) were considered biochemically disease-free (defined as a PSA nadir of 1.0 ng/ml or less) at median follow-up of 28 months. 

2.3.2   The case series of 60 patients reported positive findings in 40% (14/35) of patients who had follow-up biopsy. Eleven of these patients were treated with a second cryoablation procedure, after which 73% (8/11) were biochemically disease-free at mean follow-up of 15.2 months. Only one patient in this study had a positive biopsy result from the lobe that was treated by the procedure: all the other tumours were in the untreated lobe of the prostate.

2.3.3   In the case series of 25 patients, 28% (7/25) had repeat biopsies and residual or recurrent cancer was found in 3 of these patients. All of these patients underwent repeat cryoablation and were biochemically disease-free at median follow-up of 28 months.

2.3.1   The Specialist Advisers listed key efficacy outcomes for this procedure as biochemical disease-free survival and biopsy-proven absence of cancer.

2.4   Safety

2.4.1   In the case series of 60 patients, 40 (67%) patients who were sexually potent before treatment became impotent immediately after treatment. 71% (24/34) of patients for whom data were available at 12 months had regained potency. In the case series of 54 patients 90% (36/40) of the patients who were potent before treatment remained potent after treatment.

2.4.2   With regard to urinary continence, the case series of 54 and 25 patients reported that all patients assessed for this outcome were continent after treatment. The case series of 60 patients reported incontinence in 2/55 (4%) of the patients followed up for more than 6 months (neither required incontinence pads).

2.4.3   The case series of 54 patients reported that one patient required a transurethral prostatectomy for the removal of sloughed tissue.

2.4.4   The Specialist Advisers listed adverse events reported in the literature as erectile dysfunction and incontinence. They considered theoretical adverse events as urinary tract infection and pain.

2.5   Other comments

2.5.1   The Committee was mindful of the uncertain natural history of prostate cancer: this underpinned the recommendation for controlled studies and the need for details of long-term outcomes.

2.5.2   The Committee noted the potential for this procedure to avoid many of the complications of more radical treatments for localised prostate cancer in properly selected patients, if further evidence supports its efficacy.

2.5.3   The Committee noted a number of patient commentaries which described benefits from the procedure, but which provided evidence of occasional cases of urinary and sexual dysfunction.

2.5.4   The Committee noted variation in the methods used to deliver focal therapy using cryoablation for localised prostate cancer and that techniques are continuing to evolve.

3   Further information

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

Bruce Campbell

Chairman, Interventional Procedures Advisory Committee

November 2011

_{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.}