Chapter 95

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 therapy(ies) may be recommended based on current symptoms, the risk of developing symptoms, or death from disease in relation to death from other causes within a given time frame (Fig. 95-1). 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 intervention. For prostate malignancies, the risks of developing the disease, symptoms, or death from cancer are balanced against the morbidities of the recommended treatments and preexisting comorbidities.

###### Figure 95-1

Clinical states of prostate cancer.PSA, prostate-specific antigen.

The prostate is located in the pelvis and is surrounded by the rectum, the bladder, the periprostatic and dorsal vein complexes and neurovascular bundles 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 surrounded by fibromuscular stroma. The acinar unit includes an epithelial compartment made up of epithelial, basal, and neuroendocrine cells and separated by a basement membrane, a stromal compartment that includes fibroblasts and smooth-muscle cells. Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) are produced in the epithelial cells. Both prostate epithelial cells and stromal cells express androgen receptors (ARs) and depend on androgens for growth. Testosterone, the major circulating androgen, is converted by the enzyme5α-reductase to dihydrotestosterone in the gland.

The periurethral portion of the gland increases in size during puberty and after the age of 55 years 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).

In 2010 approximately 217,730 prostate cancer cases were diagnosed, and 32,050 men died from prostate cancer in the United States. The absolute number of prostate cancer deaths has decreased in the past 5 years, which has been attributed by some to the widespread use of PSA-based detection strategies. However, the benefit of screening on survival is unclear. The paradox of management is that although 1 in 6 men will eventually be diagnosed with the disease, and the disease remains the second leading cause of cancer deaths in men, only 1 man in 30 with prostate cancer will die of his disease.

### Epidemiology

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