What is the efficacy of brachytherapy for locally advanced disease?

The role of brachytherapy

Brachytherapy involves the implantation or insertion of small ‘sealed sources’ containing a radioactive isotope into the prostate gland either temporarily or permanently. This allows high doses of radiation to be delivered to the prostate gland while minimising doses to adjacent structures such as the rectum and bladder.

There are two main types of brachytherapy commonly used for prostate cancer in Australia:

Permanent implant brachytherapy. This involves the permanent implantation of multiple radioactive seeds (generally Iodine-125 in Australia) directly into the prostate. Seeds are placed through the perineum under ultrasound guidance. In the great majority of cases, low-dose brachytherapy is used as monotherapy for low-to-intermediate risk prostate cancer. There are some institutional series using low-dose brachytherapy as a boost following external beam radiotherapy (EBRT) for locally advanced prostate cancer, but there are no randomised trials evaluating this approach and it is largely viewed as an experimental approach.

Temporary implant brachytherapy. This involves the temporary insertion of a radioactive compound (usually Iridium-192) guided into various positions in the prostate via the placement of multiple catheters that have been placed under ultrasound guidance. It is usually performed in combination with external beam radiotherapy for patients with intermediate- and high-risk cancers. Occasionally lower activity compounds can be used in this way administering radiotherapy over longer time periods (e.g. 24-48 hours)

There is a dearth of good randomised comparative trials to assist in assessing the place of brachytherapy in the treatment of locally advanced disease. There was only one randomised controlled trial that assessed the efficacy of temporary brachytherapy in addition to external beam radiotherapy for locally advanced disease.^[1] It was a study of 104 T2-3 patients comparing the use of a temporary brachytherapy ‘boost’ with an iridium implant (35Gy given in 48 hours) in addition to a course of external beam treatment (40Gy) with external beam treatment alone (66Gy). In the brachytherapy plus EBRT arm, 17 patients (29%) experienced biochemical or clinical failure compared with 33 patients (61%) in the EBRT arm (hazard ratio=0.42; P=0.0024). While this study supported the concept that the addition of HDR like brachytherapy showed ‘efficacy’, the comparison was not useful to guide contemporary practice as the external beam radiation dose was 66Gy, which has been shown to be inferior to higher doses such as 74Gy.

The results of this and other studies comparing brachytherapy with external radiation are difficult to generalise, since they are essentially comparing the same modality packaged in different ways. There are many other parameters in radiation treatment that affect the disease control probabilities, such as total dose, radiation technique and total treatment time, in addition to the modality of radiation, that is, brachytherapy versus external beam. There are no controls for these in many studies, including the randomised controlled trial, raising the question as to whether one of these other factors might account for any difference seen between the two arms.

In addition, men with locally advanced disease in Australia are generally treated with the combination of androgen deprivation and radiation therapy. There may be interactions with this combination that further confound comparisons.

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Evidence summary and recommendations

Evidence summary	Level	References
There is a paucity of high-quality randomised trial data comparing the use of brachytherapy to surgery for the treatment of locally advanced disease, or indeed comparing the use of brachytherapy radiation to external radiation. There is one medium-quality randomised trial. It provides little evidence to guide contemporary Australian practice, except to the extent it demonstrated evidence of effect of the high dose rate boost. As a result of the study’s design it is difficult to draw comparative conclusions from this study.	II	^[1]

Evidence-based recommendation	Grade
3D conformal dose escalated external beam radiotherapy alone, or reduced dose external beam radiation treatment in combination with high dose-rate brachytherapy, are well recognised radical treatments for locally advanced disease. There is no randomised evidence to suggest superiority or to recommend one modality over the other.	D