Prostate cancer is graded according to the histologic appearance of the malignant cell and grouped into well, moderately, or poorly differentiated grades. Gland architecture is examined in two separate specimens and 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), whereas well-differentiated tumors grow slowly (better prognosis).
Metastatic spread of prostate cancer occurs by lymphatic drainage, hematogenous dissemination, or local extension. 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 dihydrotestosterone (DHT). 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.
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 is derived from direct adrenal cortical secretion of testosterone or steroids such as androstenedione.
Prostate cancers are usually identified prior to the development of symptoms because of routine screening. Prior to the implementation of routine screening, prostate cancers were frequently identified on the investigation of symptoms. On presentation, most patients with localized disease are asymptomatic. Ureteral dysfunction, frequency, hesitancy, dribbling, and impotence are common symptoms in patients with locally invasive disease. Advanced disease is accompanied with a variety of symptoms including back pain, spinal cord compression, lower extremity edema, pathologic fractures, anemia, and weight loss.
The information obtained from the diagnostic tests is used to stage the patient. There are two staging classification systems: the International Classification System (tumor, node, metastases, TNM) and the American Urologic System (AUS stages A-D). The AUS classification is the most commonly used staging system in the United States. Patients are assigned to stages A through D and corresponding subcategories based on size of the tumor (T), local or regional extension, presence of involved lymph node groups (N), and presence of metastases (M).