The National Institute for Health and Clinical Excellence is examining high dose rate brachytherapy for localised prostate cancer (in combination with external-beam radiotherapy) 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 high dose rate brachytherapy for localised prostate cancer (in combination with external-beam radiotherapy).

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The Advisory Committee will then prepare draft guidance which will be the basis for the Institute’s guidance on the use of the procedure in the NHS in England, Wales and Scotland.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: 28 February 2006

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 high dose rate brachytherapy (in combination with external-beam radiotherapy) for localised prostate cancer appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance.

A multidisciplinary team should be involved in the planning and use of this procedure. The Institute has issued cancer service guidance Improving outcomes in urological cancers (www.nice.org.uk/csguc).

Treatment options for prostate cancer depend on whether the disease is localised to the prostate gland. Current management options for localised prostate cancer include radiotherapy, radical prostatectomy and ‘watchful waiting’.

Radiation therapy can take the form of external-beam radiation radiotherapy, or brachytherapy. Brachytherapy can be given at either a low dose rate or a high dose rate.

High dose rate brachytherapy is a form of radiotherapy in which delivery of radiation is targeted directly to the prostate gland through a radiation source temporarily implanted within the prostate, as opposed to an external source.

Thin plastic tubes are inserted through the perineal skin behind the scrotum into the prostate gland. A radioactive source (a ‘seed’) is then inserted into each tube. A computer controls how long a seed remains in each of the tubes, so that the amount of radiation can be effectively targeted. This allows the tumour to be given a higher dose than the urethra and rectum. The tubes are then removed, leaving no radioactive material in the prostate gland.

In a controlled trial, overall 5-year survival with high dose rate (HDR) brachytherapy plus external-beam radiation therapy (EBRT) was found to be greater than with EBRT alone (86% and 54% respectively; p < 0.001). Across a number of case series 5-year survival after HDR brachytherapy and EBRT was estimated to be 85%, 89%, and 93%. In one series 84% (42/50) of patients survived to 7.2 years follow-up. In another case series of 611 patients, survival was calculated to be 65% at 10 years.

Five-year biochemical control (using prostate-specific antigen [PSA] measurements) has been shown to be more common with HDR brachytherapy plus EBRT than with EBRT alone (67% vs 44%; p < 0.001), and 3-year biochemical control with HDR or low dose rate brachytherapy to be similar (98% and 97% respectively). In three case series overall 5-year biochemical control was found to be 77% and 82%, and 4-year control to be 75%. One series found that only 5% (2/42) of survivors at 7.2 years had a PSA level greater than 1 ng/ml. In another series mean PSA fell from 10 to 1.1 ng/ml, and 85% (170/200) of patients achieved a PSA nadir below 1 ng/ml over 30 months of follow-up.

In a case series that reported outcomes of prostate biopsy findings following HDR brachytherapy plus EBRT there was no evidence of viable cancer in 86% (36/42) of cases; however, the accuracy of these results may have been limited by the sensitivity of the biopsy technique employed. For more details, refer to the sources of evidence (see Appendix).

The Specialist Advisors noted that the benefits of the procedure include improved biochemical and overall survival, and reduced side effects compared to other treatments.

In men who were potent at baseline, impotency occurred in 14% at 5 years, 30% at 30 months, 45% at 3 years, and 76% (31/41) at 7 years, but the definitions used to measure potency outcomes following HDR brachytherapy varied across the studies included

Urethral stricture (where it was reported separately from other urological complications) occurred in 1.5% (3/200), 4% (6/161), and 7% (17/230) of patients.

Acute urinary incontinence was reported in 11% of patients in the HDR arm of a comparative study, and there was chronic incontinence in 5% of patients at 3 years follow-up. A case series recorded grade 2 to 3 incontinence in 3% (7/230) of cases, but in another series this occurred in less than 1% (1/200) of cases.

Survival free of urinary incontinence was estimated to have been achieved in 86% of cases at 5 years in a case series of 108 patients. For more details, refer to the sources of evidence (see Appendix).

The Specialist Advisors noted that theoretical adverse events include urethritis, urethral stricture, proctosis causing constipation, incontinence, acute retention, impotence, haematuria, haematospermia, bladder, rectal and sphincter injuries, and rectourethral fistula.

The Institute has issued interventional procedures guidance on low dose rate brachytherapy for localised prostate cancer (www.nice.org.uk/IPG132).

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

Interventional procedure overviewof high dose rate brachytherapy for localised prostate cancer (in combination with external beam radiotherapy ), November 2005

Available from: www.nice.org.uk/ip309overview