The National Institute for Health and Clinical Excellence is examining cryotherapy as a primary treatment for prostate cancer 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 cryotherapy as a primary treatment for 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 preliminary recommendations
• 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• The Advisory Committee will then prepare draft guidance which will be the basis for the Institute's guidance on the use of the procedure in the NHS in England, Wales and Scotland.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 Interventional Procedures Programme manual, which is available from the Institute's website (www.nice.org.uk/ipprogrammemanual).

Closing date for comments: 21 June 2005
Target date for publication of guidance: September 2005

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 cryotherapy, measured by reduction of prostate-specific antigen (PSA) levels and biopsy findings, appears adequate to support the use of this procedure as a primary treatment in patients with prostate cancer provided that normal arrangements are in place for consent, audit and clinical governance.

Further research and audit should address quality of life, clinical outcomes and long-term survival.

Cryotherapy has been used for prostate cancer mainly as a salvage procedure for local recurrence following radiotherapy. More recently, it has been used as a primary treatment for patients with localised or locally advanced prostate cancer.

Treatment options depend on the extent of the cancer. Current treatments for localised prostate cancer include watchful management, radiotherapy and radical prostatectomy.

Cryotherapy may be performed under general or spinal anaesthesia. A warming catheter is initially inserted into the urethra to prevent it being damaged by cold. Cryoprobes are inserted into the prostate, using imaging for guidance. Temperature monitor probes may also be placed percutaneously through the perineum. Argon gas is then circulated through the cryoprobes, generating very low temperatures which freeze and destroy the affected tissue. Newer cryotherapy techniques allow these needles to be removed or repositioned so that the frozen zone conforms to the exact size and shape of the target tissue. After the procedure, a suprapubic catheter is inserted and left in place for 1-2 weeks, depending on the post-void residual urine volume.

The main outcomes reported by the studies were biopsy results and survival rates. In addition, different PSA values were used to define biochemical-free survival. In most of the studies, the procedure was used concomitantly with hormone therapy which may have an effect on the PSA levels.

One study of 975 patients reported a 5-year actuarial biochemical disease-free survival of 52% or 63%, depending on the PSA cut-off value (<0.5ng/ml and <1.0ng/ml respectively). Another study of 590 patients reported a 7-year actuarial biochemical disease-free survival between 62% and 76%, depending on the criteria used (PSA <0.5ng/ml and <1.0ng/ml respectively). The proportion of patients with a negative biopsy was 87% (514/590) after a mean follow-up of 5 years.

The main complications were impotence, affecting between 72% (39/54) and 100% (76/76) of patients, and incontinence in 1% (1/76) to 18% (10/54) of patients. However, not all studies reported the proportion of patients who were impotent or incontinent before the cryotherapy treatment. Five studies, including a total of 1891 patients, reported that between 4% (3/76) and 15% (4/27) of patients required a transurethral resection after the cryotherapy procedure. Four studies reported fistula as a complication, affecting between 0.3% (2/590) and 1.8% (1/54) of patients. Other complications included urinary tract infection, scrotal swelling, pelvic pain, penile tingling and numbness, stricture, stone formation in the prostatic urethra, bladder perforation, paraphimosis and paraesthesia in the legs. For more details, refer to the sources of evidence (see Appendix).

The Institute has issued guidance on urological cancer services (www.nice.org.uk/page.aspx?o=36469), which includes prostate cancer. The Institute has also issued interventional procedures guidance on the use of cryotherapy for recurrent prostate cancer (www.nice.org.uk/IPG119guidance), laparoscopic radical prostatectomy (www.nice.org.uk/IPG016guidance), and high-intensity ultrasound for prostate cancer (www.nice.org.uk/IPG118guidance).

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

Interventional procedure overview of cryotherapy as a primary treatment for prostate cancer, October 2004

Available from: www.nice.org.uk/ip259overview