Clinical Practice Guidelines for the management of locally advanced ...

6.4 Radiotherapy
6.4.1 External beam radiotherapy
See section 5.2 Radiotherapy
6.4.2 Radioisotopes
The administration of certain radioactive chemicals (radioisotopes) through the blood stream (as a
single dose of an intravenous injection) offers one method of dealing with patients presenting with
such multifocal pain. Such an approach has the advantage of not only relieving pain but also having
some anti-tumour effect. The two isotopes that have been used in Australia include strontium 89 and
samarium 153. The former has been more easily accessible and therefore used more commonly. These
isotopes are characterised by low radiation emissions localised to the bone and have affinity for bone,
especially honing onto areas where the affected bone responds to the presence of tumour cells by
producing reactive bony tissue. (These areas can appear as abnormal dense areas referred to as
osteoblastic metastases on X-rays.)
Nine RCTs have examined the effects of strontium 89 for the treatment of bone metastases. Two
compared strontium 89 with placebo. 46, 47 Four compared strontium 89 with active treatment arms
such as local or hemi-body irradiation 48, 49 or chemotherapy. 50, 51 Two examined the addition of
strontium 89 to local external beam radiotherapy 52-54 and two examined the addition of strontium 89 to
chemotherapy. 50, 55 The heterogeneity of study design renders low volumes of evidence about any
specific treatment. In addition, only non-taxane chemotherapy was used in the chemotherapy trials.
Therefore these trials lose their relevance in modern-day practice where taxanes are the first-line
chemotherapeutic option of choice. As a result they were not considered further in this analysis.
Four RCTs examined the effects of samarium 153 for the treatment of bone metastases. Two
randomised trials compared samarium with placebo 56, 57 and three studies compared different doses of
Samarium. 56, 58, 59 There are no randomised trials comparing samarium with other radioisotopes,
chemotherapy or external beam irradiation.
Regrettably, the majority of the remaining studies have flaws in that they have used small sample
sizes, are not head-to-head comparisons, utilise different criteria to measure response to pain, and
46, 54, 58, 59
some studies are not limited to patients with metastatic prostate cancer alone.
Furthermore, while the patients in these studies appear similar to prostate cancer patients seen in
palliative care practice, these studies were conducted in the pre-taxane chemotherapy and
bisphosphonate era. As a result, the findings may not be generalisable to current Australian medical
practice where many of the men with bone metastases might have been pre-treated with chemotherapy
(taxane-based) or bisphosphonates. The potential for increased bone marrow suppression in this
setting must to be taken into consideration before administering the radioisotope.
Pain control
There were four studies examining strontium 89 for metastatic bone pain relief. 46-48, 52, 53 These varied
in follow up, doses, regimen and endpoint reporting. The largest study with the highest dose showed a
52, 53
statistically significant decrease in analgesic use when strontium was added to local radiotherapy.
The RCT comparing strontium 89 with external beam radiotherapy suggested that these treatments
were equivalent. 48 The results of the two small placebo RCTs 46, 47 were conflicting.
The two studies comparing samarium 153 with placebo show a trend towards pain relief with
samarium 153. The prostate-cancer-specific study 57 with the largest number of participants (n=152),
showed a statistically significant benefit. All three studies examining dose show a trend towards better
pain relief with higher dose. However, the size of the effect could not be adequately assessed in two
Clinical practice guidelines for the management of locally advanced and metastatic prostate cancer
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