The National Institute for Clinical Excellence is examining secondary transperineal cryotherapy for carcinoma of the prostate 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 secondary transperineal cryotherapy for carcinoma of the prostate.

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• The Advisory Committee will then prepare draft guidance, which will be the basis for the Institute's guidance on the use of the procedure in the NHS in England, Wales and Scotland.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

Closing date for comments: 27 April 2004

Target date for publication of guidance: July 2004

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 and efficacy of secondary transperineal cryotherapy for carcinoma of the prostate does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.

Clinicians wishing to undertake secondary transperineal cryotherapy for carcinoma of the prostate should take the following action.

• Inform the clinical governance leads in their Trusts.
• Ensure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. Use of the Institute's Information for the Public is recommended.
• Audit and review clinical outcomes of all patients having secondary transperineal cryotherapy for carcinoma of the prostate.

1.3 Publication of safety and efficacy outcomes will be useful in reducing the current uncertainty. The Institute may review the procedure upon publication of further evidence.

Secondary transperineal cryotherapy may be used to treat carcinoma of the prostate that has been refractory to other treatments, most typically radiation or hormones.

Treatment options for locally recurrent prostate cancer after radiotherapy treatment are limited and include salvage radical prostatectomy, salvage cryotherapy and salvage brachytherapy.

Secondary transperineal cryotherapy may be performed under general or spinal anaesthesia. A warming catheter is initially inserted into the urethra, to prevent it being damaged by the cold. Saline is injected into Denonvilliers' fascia, temporarily increasing the space between the rectum and prostate. Cryoprobes are inserted into the prostate percutaneously through the perineum, using transrectal ultrasound for guidance. Temperature monitor probes may also be placed percutaneously through the perineum. One or two freeze-thaw cycles are then carried out, involving a distinct freezing event in which the entire prostate gland is encompassed in an iceball, followed by a period of complete thawing. After the procedure, a suprapubic catheter is inserted and left in place for 1-2 weeks, depending on the post-void residual urine volume.

Prostate specific antigen (PSA) is a protein produced by both normal and cancerous cells in the prostate gland. Changes in the PSA level may be used to monitor response to treatment.

No comparative studies were identified. Different efficacy outcome measures were used in the case series and case reports identified, making comparisons of efficacy across studies difficult. Nadir PSA < 0.5 ng/ml was reported in 97% (114/118) of patients in one study; nadir PSA < 0.4 ng/ml was reported in 37% (16/43) of patients in another; and nadir PSA < 0.3 ng/ml was reported in 36% (8/22) of patients in another. In a study of 43 patients, biochemical recurrence-free survival was reported as 79% at 6 months and 66% at 12 months, and in a study of 38 patients as 86% at 12 months and 74% at 24 months. Biochemical failure (an increase of 0.2 ng/ml or more above the nadir PSA level) was reported in 58% (85/146) of patients in one study. For more details, refer to the sources of evidence (see Appendix).

The Specialist Advisors considered there to be insufficient evidence to demonstrate efficacy for the procedure.

Among the studies identified, the following complications were reported: impotence in 72% (108/150) to 100% (11/11) of patients; incontinence in 8% (3/38) to 95% (21/22) of patients; urinary retention in 41% (9/22) of patients; perineal and/or rectal pain in 18% (27/150) to 39% (15/38) of patients; hydronephrosis in 36% (8/22) of patients; surgical death from pulmonary embolism in 4% (1/23) of patients; and fistula formation in 1% (2/150) and 3% (4/118) of patients . For more details, refer to the sources of evidence (see Appendix).

The Specialist Advisors listed the main complications as urinary incontinence, impotence, rectal injury, and fistula formation.

The Institute has issued urological cancer services guidance, which includes prostate cancer. The Institute has also issued interventional procedures guidance on laparoscopic radical prostatectomy and holmium laser prostatectomy for carcinoma of the prostate. For more details, see the NICE website www.nice.org.uk

The following document, which summarises the evidence, was considered by the Interventional Procedures Advisory Committee when making its provisional recommendations.

• Interventional procedure overview of secondary transperineal cryotherapy for carcinoma of the prostate, November 2002

Available from: www.nice.org.uk/ip130overview