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FOUNDATION OVERVIEW

Prostate cancer is the most common cancer in men. Most prostate cancers are adenocarcinomas, occurring when normal semen-secreting cells mutate into cancer cells and grow uncontrollably. Normal growth and differentiation of the prostate depends on the presence of androgens, specifically dihydrotestosterone (DHT). Androgen synthesis regulation is mediated by a negative feedback loop involving the hypothalamus, pituitary, adrenal glands, and testes. Luteinizing hormone–releasing hormone (LH-RH) is released from the hypothalamus; then 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 estradiol, while 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 pathway. 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 secretion.

Prostate cancer may present with or without symptoms, but may be identified through proper screening. On presentation, most patients with localized disease are asymptomatic. Patients with locally advanced disease, however, may present with symptoms such as ureteral dysfunction, impotence or urinary frequency, hesitancy, post-void dribbling. Advanced disease is accompanied by a variety of symptoms that may include back pain, spinal cord compression, lower extremity edema, pathologic fractures, anemia, and weight loss, depending on the sites of advanced disease. Metastatic spread of prostate cancer can occur by lymphatic drainage, hematogenous dissemination, and local extension. The pelvic and abdominal lymph node groups are the most common sites of lymph node involvement, while bone metastases are the most common sites of distant spread. The lung, liver, brain, and adrenal glands are the most common sites of visceral involvement.

After biopsy, prostate cancer is graded according to the histologic appearance of the malignant cell and grouped into one of three grades: well, moderately, or poorly differentiated. The Gleason grading system correlates the histological features of the biopsy with clinical behavior. Gland architecture is examined by reviewing two separate specimens, each rated on a scale of 1 (well differentiated) to 5 (poorly differentiated). The grades of each individual specimen are added together to determine the Gleason score. Groupings for total Gleason score are 2 to 4 for well-differentiated, 5 to 6 for moderately differentiated, and 7 to 10 for poorly differentiated tumors. Poorly differentiated tumors grow rapidly, portending a poor prognosis, while well-differentiated tumors grow slowly, resulting in a more favorable prognosis.

Information obtained from the biopsies and imaging studies is used to stage the patient, which is accomplished via the American Joint Committee on Cancer's TNM (tumor, node, metastases) system. In the TNM staging system, patients are assigned to stages 1 through 4 with corresponding subcategories based on size of the tumor (T), local ...

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