Managing metastatic bone pain

Patients associate advanced cancer with pain, and for many such patients the source of the pain will be metastatic bone disease. Bone is one of the most frequent sites of spread for many common cancers such as breast, prostate, lung, and kidney and is usually affected in multiple myeloma.¹ Active management of metastatic bone disease can, however, control the symptoms and in many cases prevent further complications such as pathological fracture or compression of the spinal cord.²

What can be done? Firstly, patients should be given analgesics and considered for appropriate systemic treatment for the underlying cancer, usually hormonal treatment or chemotherapy. Secondly, patients should be considered for specific treatment for the bone metastases, the principal modalities being radiotherapy and bisphosphonates.

Radiotherapy has long been used. It is most commonly given as external beam to the most painful site or sites. Does it work, and how should it be given? Assessing reduction in pain in patients with advanced cancer is difficult because of changes in their analgesia, changes in the cancer itself, and high dropout rates in patients with advanced cancer. Nevertheless, the data on fractionation trials have been subjected to two overviews (and, for aficionados, an overview of the overviews).^3-5 Both overviews are consistent and show a response rate (pain reduction) in about 60% of patients, which is complete in about 33% (and rises to about 72% and 40%, respectively, if the analysis is of evaluable patients rather than on an intention to treat basis). These response rates are the same whether the radiotherapy is given as a single fraction (usually 8-10 Gy) or as multiple fractions (most commonly 20-30 Gy in 5-10 fractions). The pressure on facilities for radiotherapy in the United Kingdom as well as convenience for the patient in attending only once are strong arguments to use single fractions.⁶ The main difference between single and multiple fractions is the higher rate of repeated treatment in the single fraction studies (21.5% v 7.4%). The higher re-treatment rate in the single fraction arms may not necessarily lower therapeutic efficacy since time to progression was the same in those studies that examined it. Rather, it may reflect clinicians' greater willingness to repeat treatment after a single rather than after the higher dose of multiple fractions. Whatever the reason, even with single fractions, nearly 80% of patients will not need repeat treatment.

For some patients, especially for those with cancer of the prostate, using a radioisotope such as strontium 89 that localises to bone will relieve pain, albeit with risk of leucopenia and thrombocytopenia.⁷

Given that most patients will have multiple bony metastases, what are the systemic options specifically for treating bone metastases? The most widely used agents are bisphosphonates, for which good evidence indicates that they will reduce the incidence of fractures, the need for palliative radiotherapy, the risk of hypercalcaemia, and the need for orthopaedic surgery (often collectively called skeletal related events), but not the risk of compression of the spinal cord.⁸ These benefits are seen mainly after six months of treatment, and the reduction in orthopaedic surgery is appreciable only at 24 months. Most of the trials included patients with metastatic breast cancer or multiple myeloma, with more limited data on patients with prostate cancer. Although bisphosphonates presumably work in a similar way in patients with bone metastases from other sites, the benefits may not be apparent since their survival is much shorter. Many studies have concentrated on assessing events related to the skeleton rather than on pain itself, but most clinicians would regard reductions in fractures and need for radiotherapy as good surrogate markers of a reduction in pain. These data are confirmed in a specific overview.⁹ Pamidronate has been the bisphosphonate most widely used, but newer third generation bisphosphonates (zelodronate, ibandronate) have been the subject of more recent studies.

Back pain merits a particular mention. If the patient describes a notable increase in the severity of the pain and a new severe nerve root pain (often describing it as “shooting,” “sharp,” or “like pins and needles”) then an epidural component and a risk of spinal cord compression may be present. Traditionally, many patients are left until they develop neurological signs of paraplegia, by which time many will never walk again. The above symptoms in a patient with cancer are an indication for an urgent magnetic resonance scan and treatment (radiotherapy, surgery), to help the patient's pain and preserve his or her mobility.¹⁰

We can help patients with metastatic bone disease. Pain can dominate the lives of patients and their families; we owe it to them to use all therapeutic options to control the pain. A clear management plan developed between patient, general practitioner, and oncologist will control the pain and often give patients the confidence to cope with their illness.