Prostate cancer is a continuum, progressing through localized, locally advanced, advanced metastatic, and hormone-refractory stages. It is generally a slow-growing cancer, primarily under hormonal control, that is, testosterone. Grading schemes include the American Urological System, widely used in the United States (stages A, B, C and D), the tumor-node-metastasis (TNM) prostate classification, and the Gleason score. Major stages, described by tumor size and extent, include tumors that are:

• Nonpalpable, cannot be clinically assessed
• Confined to prostate, may or may not be palpable
• Localized around the prostate area, may or may not extend to adjacent areas, and
• Metastatic

Of concern in this website is advanced metastatic prostate cancer with its consequences to skeletal wellness.

Prostate cancer is usually asymptomatic in its early stages; but advanced prostate cancer may show ureteral obstruction caused by ureterovesical junction compression by a tumor or nodal metastases. Hyponephrosis can then develop, affecting the function of the associated kidney. Back pain may be the result of vertebral body metastases, with the potential for spinal cord compression. Local pain may originate from cancer in the prostate gland and cancer invasion into the surrounding tissues; referred pain may appear in the legs and abdomen. Problematic bone pain may indicate additional skeletal metastases, and involvement may then include hips, legs, neck, shoulders, and ribs. Other symptoms of advanced prostate cancer growth include weight loss, rectal obstruction from local growth, coagulation deficits, hypercalcemia, leg edema from nodal metastases, and pancytopenia from metastases in the marrow.^1,2

Skeletal-related events are the clinical complications of bone metastases in patients with advanced cancer.

• Pathologic fracture may result in bone eroded by metastasis, such that a slight trauma is sufficient to break the bone and cause pain, loss of mobility, and the need for possible surgical intervention.
• In vertebral metastases, the vertebral body may collapse, causing the tissue mass to bulge into the spinal canal, compressing the spinal cord. This may result in paralysis and, certainly, pain.
• Unlike traumatic fractures, pathologic fractures do not heal spontaneously when immobilized but rather require additional surgical procedures. Radiotherapy may be needed to eradicate tumor tissue, prevent further fracture, and relieve pain.
• Hypercalcemia of malignancy may be a late complication of cancer, causing nausea, vomiting, dehydration, weakness, and coma, and culminating in death.

Skeletal complications are a significant cause of patient morbidity, leading to considerable pain and hindering a patient's ability to perform basic functions. These skeletal events, even in early development, also negatively impact the social and emotional functions of patients' lives and greatly impair their quality of life. Skeletal metastases are associated with poor prognosis.

Cancer patients without bone metastases^3-5 are also at higher risk for bone loss resulting from:

• Treatment-related osteoporosis (or cancer-treatment–induced bone loss, another commonly used term), resulting especially from androgen deprivation therapy for prostate cancer (see Treatment Section)
  – Results in
     - Decreased bone mineral density
     - Increased risk of osteoporotic bone fractures
• Induction of generalized bone loss (osteoporosis/osteopenia)

This increase in osteoporosis in men results in greater numbers of hip fractures and a high annual cost to the US healthcare system. Recovery from hip fractures is especially difficult for men and usually incomplete. Approximately one third of men die within 1 year of fracture.⁶

1.	Surya BV, Provet JA. Manifestations of advanced prostate cancer: prognosis and treatment. J Urol. 1989;142:921-928.
2.	Payne R. Pain management in the patient with prostate cancer. Cancer 1993;71(suppl 3):1131-1137
3.	Mundy GR. The evolving role of bisphosphonates: cancer treatment-induced bone loss. Oncology. 2004;18(suppl 3):9-10.
4.	Theriault RL. Pathophysiology and implications of cancer treatment-induced bone loss. Oncology. 2004; 18(suppl 3):11-15.
5.	Smith MR. Management of treatment-related osteoporosis in men with prostate cancer. Cancer Treat Rev. 2003;29:211-218.
6.	National Institutes of Health, Osteoporosis and Related Bone Diseases, National Resource Center. Osteoporosis Overview. (Fact Sheet). Bethesda, Md. National Institutes of Health. January 2003. Available at http://www.osteo.org/newfile.asp? doc=osteo&doctitle=Osteoporosis+Overview&doctype=HTML+Fact Sheet. Accessed December 2, 2004.