In the United States alone, it is estimated that 192,280 new cases of prostate cancer will be diagnosed and more than 27,360 men will die from this disease in 2009.1 Although prostate cancer incidence increased during the late 1980s and early 1990s owing to widespread prostate-specific antigen (PSA) screening, deaths from prostate cancer have been declining since 1995.1
The widely accepted risk factors for prostate cancer are age, race-ethnicity (African American ancestry), and family history of prostate cancer.2,3 The disease is rare under the age of 40, but the incidence sharply increases with each subsequent decade, most likely because the individual has had a lifetime exposure to testosterone, a known growth signal for the prostate.3
The prostate gland is a solid, rounded, heart-shaped organ positioned between the neck of the bladder and the urogenital diaphragm. Adenocarcinoma, the major pathologic cell type, accounts for more than 95% of prostate cancer cases.4,5 Prostate cancer can be graded systematically according to the histologic appearance of the malignant cell and then grouped into well, moderately, or poorly differentiated grades.5,6 Gland architecture is examined in two separate specimens and then rated on a scale of 1 (well differentiated) to 5 (poorly differentiated). The grades of each specimen are added together to determine the Gleason score. Groupings for total Gleason score are 2 to 4 for well-differentiated, 5 or 6 for moderately differentiated, and 7 to 10 for poorly differentiated tumors. Poorly differentiated tumors grow rapidly (poor prognosis), while well-differentiated tumors grow slowly (better prognosis).5,6
Metastatic spread can occur by lymphatic drainage, hematogenous dissemination, or local extension.6,7 The pelvic and abdominal lymph node groups are the most common sites of lymph node involvement. Bone metastases from hematogenous spread are the most common sites of distant spread. The lung, liver, brain, and adrenal glands are the most common sites of visceral involvement.
Normal growth and differentiation of the prostate depends on the presence of androgens, specifically dihydrotesterone (DHT).7,8 The testes and the adrenal glands are the major sources of circulating androgens. Hormonal regulation of androgen synthesis is mediated by a negative feedback loop involving the hypothalamus, pituitary, adrenal glands, and testes. Luteinizing hormone–releasing hormone (LH-RH) released from the hypothalamus stimulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gland. LH stimulates the production of testosterone and small amounts of estrogen. FSH acts on the Sertoli cells within the testes to promote the maturation of LH receptors and to produce an androgen-binding protein. Circulating testosterone and estradiol influence the synthesis of the hormones involved in the negative feedback.9
Testosterone, the major androgenic hormone, accounts for 95% of the androgen concentration. The primary source of testosterone is the testes; however, 3% to 5% of the testosterone concentration ...