An overview of treating bone metastases in men with prostate cancer.

1. Part of the “Enhancing Prostate Cancer Care” MOOC
Catherine Holborn
Senior Lecturer in Radiotherapy & Oncology
Sheffield Hallam University

2. Introduction
This presentation provides a brief overview of the treatment
of bone metastases with particular reference to prostate
cancer.
It focuses on the treatments used to treat and also provide
relief from the pain and other symptoms associated with bone
metastases.
Other treatments used in the overall management of
advanced/metastatic prostate cancer e.g. chemotherapy and
hormone therapy (androgen deprivation) will also help to
'treat/control' the metastatic disease. These have been
covered in a separate presentation.

3. Development of bone metastases
Most common site of metastases for prostate cancer
Most likely in men with castrate resistant prostate cancer
There is a correlation between the incidence of bone
metastases and initial PSA, stage and Gleason grade
The risk of development following radical surgery or
radiotherapy is less common but similar risk factors apply
If biochemical failure occurs during treatment with
hormone therapy (androgen deprivation therapy), the
risk of later developing bone metastases is also much
greater

4. Clinical characteristics
Mostly occur in the axial skeleton
They contain ‘osteoclastic’ (lytic appearance) and
‘osteoblastic’ (sclerotic appearance) areas
Osteoblastic (areas of new bone formation) predominates, but
the new bone lacks the strength of normal bone, hence the
occurrence/risk of pathological fractures
Osteoblastic activity facilities the use of radioisotope tracers
as they are drawn into the areas of new bone. Diagnostic
scanning can be used to detect even asymptomatic lesions.
This preferential uptake can also be used as a ‘systemic’
treatment using high doses e.g. the radioisotope Strontium 89
and more recently Radium 223

5. Symptoms of bone metastases
Significant pain (intermittent or constant)
A very common symptom for men with symptomatic metastatic
prostate cancer
Bone marrow suppression
Possible resulting anaemia
Hypercalcaemia
Breakdown of bone/excess bone re-absorption with 'osteoclastic'
lesions
Pathological fracture
Man may present with this, visible/detected on a plain x-ray
Spinal cord/ nerve root compression
An oncological emergency
They can have significant impact on quality of life.

6. Investigations
Cord compressions must be confirmed with an MRI scan
Men with castrate resistant prostate cancer and
extensive spinal mets should have a spinal MRI if they
are symptomatic (NICE 2008/2014 recommendation, UK)
Bone scan (radioisotope scanning)
Clinical history and physical examination to identify sites
of pain and also rule out the possibility of false positives
following a bone scan which can also show up other
morbidities such as arthritis, bony infection or
inflammatory disease
A plain radiograph may confirm the presence of a mass

7. Local treatment: External Beam RT
An effective method of pain relief
8Gy in 1# (treatment) is often favoured in the UK
Other countries may favour a slightly longer # regime e.g.
20Gy in 5#
Single fraction regimes will be avoided with larger fields e.g. a
field covering several spinal vertebrae
RT for whole pelvis/ abdomen, can be used for wide spread mets
but careful consideration should be given to the normal tissue
toxicity
Low dose/single fraction regimes are seen as a useful option
in the re-treatment of persistent disease
In cases where either is an option, studies have demonstrated
single fraction regimes to be equally as effective. One hospital
visit is seen as appealing to the patient

8. Systemic treatment: Radioisotopes
All 'systemic' treatments will be useful for treating
widespread disease
Radioisotope treatment involves the uptake of low dose
radiation, preferentially absorbed by the osteoblastic
lesions, compared to normal bone
The effectiveness of treatment depends on the intensity
of uptake and the timescale with which the
radioisotope / pharmaceutical remains within the target
tissue
This may be an option for castrate resistant patients with
painful bony mets, especially when chemotherapy is not
an option

9. Radioisotopes used
Strontium-89 is the isotope that has been traditionally, and is
most commonly, used.
It remains in the tumour for up to 100 days.
It is effective at providing pain relief in many men.
More recently Radium-223 has been investigated.
In a recent analysis, with castrate resistant men who were
symptomatic and had either already received docetaxel, were
not suitable for it, or had declined it; radium-223
demonstrated a statistically significant improvement in overall
survival and benefits in terms of skeletal related events and
other biochemical endpoints, when compared to a placebo.
Reference
Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fossa SD et al. Alpha Emitter Radium-223 and Survival in
Metastatic Prostate Cancer. The New England Journal of Medicine. 2013; 369(3): 213-223

10. Systemic treatment: Bisphosphonates
These are most effective in the presence of osteolytic bone
mets (where bone and calcium re-absorption occurs); and so
are questionable in the treatment of metastatic prostate
cancer (predominantly osteoblastic)
Osteolytic lesions are a result of increased bone destruction
and a lack of balance between this and new bone formation
(osteoblastic activity). Bisphosphonates help to rebalance
these two processes
Suppression of bone reabsorption is associated with a
significant decrease in bone pain and analgesic consumption
Initial high doses are followed by maintenance doses
Most likely to be considered for men with castrate resistant
prostate cancer, for the relief of symptoms, when other
treatments have not really worked

11. Prevention
Some research has been undertaken to investigate the benefits of
'preventing' bone related complications, as opposed to waiting to
treat them, when they arise.
The UK based TRAPEZE trial looked at the use of Strontium-89
and/or zoledronic acid delivered during treatment with docetaxel
Strontium-89 was shown to significant increase bony clinical
progression free survival
Zoledronic acid increased the skeletal related event (SRE) free
interval and decreased the total number of SREs, mostly post
progression
Neither had an impact on overall survival
Reference
N. D. James, S. Pirrie, D. Barton, et al. Clinical outcomes in patients with castrate-refractory prostate
cancer (CRPC) metastatic to bone randomized in the factorial TRAPEZE trial to docetaxel (D) with
strontium-89 (Sr89), zoledronic acid (ZA), neither, or both (ISRCTN 12808747). Journal of Clinical
Oncology. 2013. ASCO Annual Meeting Abstracts. 31 (18) June 20 Supplement. LBA5000

12. Further resources are provide in a separate resource on other
symptoms related to advanced/metastatic prostate cancer and
its management.