Prostate Specific Antigen

Prostate-specific antigen (PSA) is a glycoprotein protease enzyme produced by the epithelial cells of the prostate. This protein circulates in the serum and can become elevated because of benign and malignant conditions of the prostate. From 50% to 90% of PSA is protein bound and the remainder is free. PSA is used as a tumor maker for the screening, diagnosis, and management of prostate cancer. PSA lacks specificity for cancer, however, because it can be elevated in benign conditions such as benign prostatic hypertrophy (BPH). Estimates suggest that a PSA higher than 4 ng/mL has sensitivity of 70% to 80% and specificity of 60% to 70% for prostate cancer. Factors other than prostate cancer can affect the PSA level (Table 15-21). Controversy surrounds the effect of the digital rectal examination (DRE) on PSA. Theoretically, digitally palpating the prostate gland should elevate the serum PSA. However, it appears that PSA elevations after DRE are probably not significant, so there is no recommendation to withhold PSA testing immediately after DRE.

Although elevations of the PSA are associated with increased risk of prostate cancer, the upper limit of normal of 4 ng/mL may be somewhat arbitrary. During an initial screening examination, prostate cancer was found in 27% of men with PSA levels of 4.1 to 9.9 ng/mL and 59% with PSA over 10 ng/mL (Hernandez and Thompson, 2004). However, prostate cancer is found in 23.9% of men with PSA of 2.1 to 3.0 ng/mL and 26.9% with PSA of 3.1 to 4.0 ng/mL (Thompson et al., 2004).

The positive predictive value (PPV) of the PSA is improved if used complementary to DRE (Table 15-22). The PPV is doubled if the patient also has an abnormal DRE. A normal PSA does not exclude cancer; 20% to 40% of men with organ-confined prostate cancer will have PSA within the reference range. One report of men with confirmed, untreated, clinically significant prostate cancer found these PSA values: less than 4 ng/mL (27%), 4 to 10 ng/mL (21%), 10 to 20 ng/ mL (16%), and greater than 20 ng/mL (36%).

The use of PSA for screening for prostate cancer remains controversial. Although it is clear that PSA testing can lead to earlier detection of prostate cancer, it is not clear that early diagnosis and treatment offers significant reduction in prostate cancer mortality. Given that the lifetime risk of death from prostate cancer is only 3% in U.S. men, a large portion of men detected by screening may not have clinically significant disease.

In addition to screening, PSA is used to monitor the response to treatment for localized prostate cancer. After radical prostatectomy, PSA levels should become undetectable. Any detectable levels suggest residual or recurrent tumor and may occur months or years before it becomes clinically apparent. PSA levels fall after radiation therapy, although usually do not become

Table 15-20 Causes of Abnormal Potassium Levels

Hyperkalemia

Renal losses

Pseudohyperkalemia

Diuresis

Thrombocytosis

Renal tubular acidosis (proximal, distal)

Leukocytosis

Hypomagnesemia

Prolonged tourniquet use during venipuncture

Hyperaldosteronism

Hemolysis

Cushing's syndrome

Reduced excretion

Nonrenal losses

Oliguria

Diarrhea

Renal failure

Vomiting

Hyporeninemic hypoaldosteronism

Periodic paralysis

Adrenal insufficiency

Burns

Type IV renal tubular acidosis

Cellular shifts

Cellular shifts

Alkalosis

Acute acidosis

Beta-adrenergic therapy

Insulin deficiency

Catecholamine excess

Rhabdomyolysis

Drugs

Drugs

Thiazide diuretics

Beta blockers

Loop diuretics

ACE inhibitors

Epinephrine

Angiotensin receptor blockers

Albuterol

Spironolactone

Carbenicillin

Triamterene

Ticarcillin

Amiloride

Licorice

NSAIDs

Glucocorticoids

Heparin

Mineralocorticoids

Cyclosporine

Pentamidine

Hypokalemia

Inadequate diet

Malnutrition

Alcoholism

ACE, Angiotensin-converting enzyme; NSAIDs, nonsteroidal anti-inflammatory drugs.

undetectable. A PSA recurrence has been defined as three successive increases in the PSA level after radiation therapy.

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