Part of the “Enhancing Prostate Cancer Care” MOOC

Catherine HolbornSenior Lecturer in Radiotherapy & Oncology

Sheffield Hallam University

IntroductionThis 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.

Development of bone metastasesMost common site of metastases for prostate cancerMost likely in men with castrate resistant prostate cancerThere is a correlation between the incidence of bone

metastases and initial PSA, stage and Gleason gradeThe risk of development following radical surgery or

radiotherapy is less common but similar risk factors applyIf biochemical failure occurs during treatment with

hormone therapy (androgen deprivation therapy), the risk of later developing bone metastases is also much greater

Clinical characteristicsMostly occur in the axial skeletonThey contain ‘osteoclastic’ (lytic appearance) and

‘osteoblastic’ (sclerotic appearance) areasOsteoblastic (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

Symptoms of bone metastasesSignificant pain (intermittent or constant)

A very common symptom for men with symptomatic metastatic prostate cancer

Bone marrow suppressionPossible resulting anaemia

HypercalcaemiaBreakdown of bone/excess bone re-absorption with 'osteoclastic'

lesionsPathological fracture

Man may present with this, visible/detected on a plain x-raySpinal cord/ nerve root compression

An oncological emergency

They can have significant impact on quality of life.

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

Local treatment: External Beam RTAn effective method of pain relief 8Gy in 1# (treatment) is often favoured in the UKOther 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

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

Radioisotopes usedStrontium-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.

ReferenceParker 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

Systemic treatment: BisphosphonatesThese 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

PreventionSome 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

ReferenceN. 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

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