Bone metastases: pathophysiology and management policy.

The pathophysiology and options for management of bone metastases as well as criteria for determining response to therapy are reviewed. Bone metastases are frequently one of the first signs of disseminated disease in cancer patients. In the majority of patients, the primary tumor is in the breast, prostate, or lungs. Although almost all patients will die of their disease, a proportion of the patients will survive for several years. Treatment is primarily palliative: the intention is to relieve pain, prevent fractures, maintain activity and mobility, and, if possible, to prolong survival. Therapeutic options include local treatment with radiotherapy and/or surgery, and systemic treatment using chemotherapy, endocrine therapy, radioisotopes, agents such as diphosphonates, which inhibit resorption of bone, as well as analgesic and antiinflammatory drugs. The mechanisms by which pain is relieved by several of these therapies remain unclear but actions beyond a simple tumoricidal effect appear to be important. There have been few randomized trials comparing the therapeutic options, and the criteria for assessing response to therapy have, in general, been poorly defined. There is a need for rigorous clinical investigations that assess the efficacy of the various therapeutic possibilities by using well-defined and validated criteria of response.