Chapter 091. Benign and Malignant Diseases of the Prostate (Part 1)

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Harrison's Internal Medicine Chapter 91. Benign and Malignant Diseases of the Prostate Benign and Malignant Diseases of the Prostate: Introduction Benign and malignant changes in the prostate increase with age. Autopsies of men in the eighth decade of life show hyperplastic changes in 90% and malignant changes in 70% of individuals. The high prevalence of these diseases among the elderly, who often have competing causes of morbidity and mortality, mandates a risk-adapted approach to diagnosis and treatment. This can be achieved by considering these diseases as a series of states. Each state represents a distinct clinical milestone for which intervention(s)...

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Chapter 091. Benign and Malignant Diseases of the Prostate (Part 1) Harrison's Internal Medicine > Chapter 91. Benign and Malignant Diseases of the Prostate Benign and Malignant Diseases of the Prostate: Introduction Benign and malignant changes in the prostate increase with age. Autopsies of men in the eighth decade of life show hyperplastic changes in >90% and malignant changes in >70% of individuals. The high prevalence of these diseases among the elderly, who often have competing causes of morbidity and mortality, mandates a risk-adapted approach to diagnosis and treatment. This can be achieved by considering these diseases as a series of states. Each state represents a distinct clinical milestone for which intervention(s) may be recommended based on current symptoms or the risk of developing symptoms or death from disease
within a given time frame (Fig. 91-1). For benign proliferative disorders, symptoms of urinary frequency, infection, and potential for obstruction are weighed against the side effects and complications of medical or surgical therapy. For prostate malignancies, the risks of developing the disease, symptoms, or death from cancer are balanced against the morbidities of the interventions recommended and preexisting comorbid conditions. Figure 91-1 Clinical states of prostate cancer. PSA, prostate-specific antigen. Anatomy and Pathology The prostate is located in the pelvis and is surrounded by the rectum, the bladder, the periprostatic and dorsal vein complexes that are responsible for erectile function, and the urinary sphincter that is responsible for passive urinary control. The prostate is composed of branching tubuloalveolar glands arranged in lobules and surrounded by a stroma. The acinal unit includes an epithelial
compartment made up of epithelial, basal, and neuroendocrine cells and a stromal compartment that includes fibroblasts and smooth-muscle cells. The compartments are separated by a basement membrane. Prostate-specific antigen (PSA) and acid phosphatase are produced in the epithelial cells. Both prostate epithelial cells and stromal cells express androgen receptors and depend on androgens for growth. Testosterone, the major circulating androgen, is converted by the enzyme 5α- reductase to dihydrotestosterone in the gland. The periurethral portion of the gland increases in size during puberty and after the age of 55 due to the growth of nonmalignant cells in the transition zone of the prostate that surrounds the urethra. Most cancers develop in the peripheral zone, and cancers in this location can often be palpated during a digital rectal examination (DRE). Prostate Cancer In 2007 in the United States, ~218,890 prostate cancer cases were diagnosed, and 27,050 men died from prostate cancer. The absolute number of prostate cancer deaths has decreased in the past 5 years; this has been attributed by some to the widespread use of PSA-based detection strategies. However, screening has not been shown to improve survival in prospective randomized trials. The paradox of management is that although the disease remains the second leading
cause of cancer deaths in men, only 1 man in 8 with prostate cancer will die of his disease. Epidemiology Epidemiologic studies show that the risk of being diagnosed with prostate cancer increases by a factor of 2 if one first-degree relative is affected and by 4 if two or more are affected. Current estimates are that 40% of early-onset and 5–10% of all prostate cancers are hereditary. Prostate cancer affects ethnic groups differently. Matched for age, African-American males compared to white males have both a greater number of prostatic intraepithelial neoplasia (PIN) lesions, which are precursors to cancer, and larger tumors, possibly related to the higher levels of testosterone seen in African-American males. PIN, the precursor of cancer, is typically multifocal and highly unstable. Polymorphic variants of the androgen receptor gene, the cytochrome P450 C17 gene, and the steroid 5α- reductase type II (SRD5A2) gene have also been implicated in the variations in incidence. The incidence of autopsy-detected cancers is similar around the world, while the incidence of clinical disease varies. Thus, environmental factors may play a role. High consumption of dietary fats, such as α-linoleic acid, or the polycyclic aromatic hydrocarbons that form when red meats are cooked is believed to increase risk. Similar to breast cancer in Asian women, the risk of
prostate cancer in Asian men increases when they move to Western environments. Protective factors include consumption of the isoflavinoid genistein (which inhibits 5α-reductase), cruciferous vegetables that contain the isothiocyanate sulforaphane, retinoids such as lycopene (in tomatoes), and inhibitors of cholesterol biosynthesis (e.g., statin drugs). The antioxidants α-tocopherol (vitamin E) and selenium may also reduce risk. The development of a prostate cancer is a multistep process. One early change is hypermethylation of the GSTP1 gene promoter, which leads to loss of function of a gene that detoxifies carcinogens. A role for inflammation has been suggested based on the finding that many prostate cancers occur adjacent to a lesion termed PIA (proliferative-inflammatory atrophy). This also suggests a role for oxidative damage.