2 Clinical need and practice

2 Clinical need and practice

2.1 Bone is one of the most common sites for circulating cancer cells to settle and start growing. Metastases can occur in any bones in the body, but the spine is commonly affected, as well as the pelvis, hip, upper leg bones and the skull. Almost any cancer can metastasise to the bone, but cancers of the breast, prostate, lung, bladder, thyroid and kidney spread to the bone most often.

2.2 The manufacturer has estimated that there are more than 150,000 people in England and Wales with solid tumours and bone metastases, more than 80% of them with breast and prostate cancer. Approximately 0.5% of women with breast cancer have bone metastases at diagnosis and 4.7% develop bone metastases within 5 years. The manufacturer's submission reported that 11% of people with prostate cancer present with bone metastases at initial staging.

2.3 In women with breast cancer, bone metastases are associated with a median reduction in survival of approximately 2 years. In men with prostate cancer, bone metastases are associated with a reduced 5-year survival from 56% to 3%.

2.4 Bone metastases are also associated with reduced quality of life and an increased risk of complications from bone weakness or disrupted calcium homeostasis. Complications include pathological fractures (defined as pathological because minimal or no force is needed to cause them), spinal cord compression, radiation to the bone or surgery to the bone. These are collectively defined as skeletal-related events. Mobility may be reduced because of bone pain and other complications. Metastatic bone pain can be intermittent or constant, and people with bone metastases often report inadequate pain relief with analgesics.

2.5 The primary aim of treating bone metastases is to manage skeletal morbidity by delaying or preventing skeletal-related events. A second aim is to delay pain and reduce its severity. Current treatments for bone metastases and their complications include radiotherapy, orthopaedic surgery, bone-targeting radio-pharmaceuticals and chemotherapy. Four bisphosphonates have a marketing authorisation for managing bone metastases or preventing skeletal-related events in people with solid tumours: zoledronic acid, disodium pamidronate, sodium clodronate and ibandronic acid. Zoledronic acid is the only bisphosphonate that has a marketing authorisation for the prevention of skeletal-related events in advanced malignancies involving bone without specifying the primary tumour type. Disodium pamidronate and sodium clodronate have a marketing authorisation for breast cancer and multiple myeloma, and ibandronic acid has a marketing authorisation for breast cancer only.

2.6 Management of bone metastases varies by primary cancer type. Advanced breast cancer: diagnosis and treatment (NICE clinical guideline 81) recommends offering bisphosphonates to people with newly diagnosed breast cancer and bone metastases to prevent skeletal-related events and reduce pain. Prostate cancer: diagnosis and treatment (NICE clinical guideline 58) does not recommend the use of bisphosphonates to prevent or reduce complications of bone metastases in men with hormone refractory prostate cancer. In this patient group, bisphosphonates for pain relief may be considered when other treatments, including analgesics and palliative radiotherapy, have failed. The oral or intravenous route of administration should be chosen according to convenience, tolerability and cost. In people with lung cancer with bone metastases who need palliation and for whom standard analgesic treatments are inadequate, single-fraction radiotherapy is recommended (Lung cancer: the diagnosis and treatment of lung cancer [NICE clinical guideline 121]). Metastatic spinal cord compression: diagnosis and management of adults at risk of and with metastatic spinal cord compression (NICE clinical guideline 75) recommends bisphosphonates in people with breast cancer or multiple myeloma with vertebral involvement to reduce pain and the risk of vertebral fracture/collapse. In people with vertebral involvement from prostate cancer, bisphosphonates are recommended to reduce pain only if conventional analgesia fails to control pain.

  • National Institute for Health and Care Excellence (NICE)