Health and Prostate

Pathophysiology of the Prostate Gland: Benign Prostatic Hyperplasia and Cancer

The prostate is a small, walnut-shaped gland that lies below the urinary bladder and surrounds the urethra. The gland secretes a fluid that accounts for about 30% of the volume of semen and functions to lubricate the urethra and increase sperm motility. As a man ages, his prostate grows. Growths can be either benign (benign prostatic hyperplasia, or BPH) or malignant. If malignant, they can have an indolent course, or they can metastasize and become life-threatening.

Benign prostatic hyperplasia is characterized by histologic changes in the prostate (hyperplastic nodules in the periurethral area) that result from prolonged exposure to androgens. There is both a static and a dynamic component to prostate enlargement; the static component is related to the increase in prostate size due to proliferation of smooth muscle cells in the prostatic stroma, and the dynamic component, to the increase in smooth muscle tone in the prostate and bladder neck. Symptoms due to obstruction include urinary hesitancy, intermittency, and dribbling, weak force of the urinary stream, and incomplete emptying. Irritative symptoms include nocturia, daytime frequency, urgency, and burning. Prolonged urinary retention can result in progressive renal failure, azotemia, and hematuria. BPH afflicts an estimated 14 million American men, including more than 50% of men older than 60 years of age. Indeed, almost all men will have benign prostatic hyperplasia if they live long enough. Annual costs in the United States for BPH are approaching $2 billion, yet only a fraction of affected men are receiving treatment.

Prostate cancer is a malignant tumor that arises in the cells lining the prostate gland. An estimated 318,000 patients will develop new prostate cancer this year, and more than 40,000 will die of the disease, making prostate cancer the most common new cancer diagnosed in American men; it is second only to lung cancer as the leading cause of male cancer death. The cancer may remain within the prostate, or it may spread to surrounding tissues or to distant sites (most often lymph nodes and bone). Usually prostate cancer spreads silently, producing symptoms only when it has progressed beyond the prostate. Initial symptoms are the same as for benign prostatic hyperplasia: urinary frequency, hesitancy, and weak stream, and nocturia, dysuria, and hematuria. If the malignancy has metastasized to the bones, bone pain may occur, especially in the backbone, pelvis, hips, or ribs. The single greatest risk factor for prostate cancer is age; 80% of men with prostate cancer are 60 years of age and older.

Why some men experience only benign enlargement of the prostate, and others develop a malignancy, is poorly understood. Nor is it understood why some cancers are slow-growing and cause no symptoms for prolonged periods, whereas others are aggressive and rapidly fatal. Even cancer cells from a single biopsy specimen show histologic differences. Some cells are androgen dependent and can be destroyed by antiandrogen therapy; others are androgen independent. Androgen independence can arise from a mutation in the gene that codes for the androgen receptor. Taplin et al found that some of these mutations are caused by amino acid substitutions in the hormone-binding domain of the receptor, so that the receptor loses specificity and responds to other hormones, such as estradiol and progesterone and even antiandrogens, such as flutamide (Eulexin/Schering), that are used to treat prostate cancer. Indeed, antiandrogen treatment itself may favor the growth cells with mutant androgen receptor genes. (Taplin M-E, et al. N Engl J Med. 199;332:1393-1398.)

The American Cancer Society recommends that all men between the ages of 50 and 70 be screened annually for prostate cancer (black men and men with a family history of prostate cancer should start annual screenings at the age of 40). Screening includes two tests: a digital rectal examination and a prostate-specific antigen (PSA) blood test. Together, these two tests effectively detect prostate cancer at an early stage, which allows for more choices in treatment and a greater chance of cure.

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