[MIM*176807] a malignant neoplasm arising from glandular epithelial cells of the prostate gland.Prostatic adenocarcinoma (PA) is the most commonly occurring visceral cancer in men, and it ranks second only to lung cancer as a cause of cancer deaths in men. Each year, 190,000 new cases are diagnosed in the U.S., and more than 30,000 men die of the disease. Foci of PA are found at autopsy in 40% of men dying after age 50. In the U.S. a man has a 15% lifetime risk of being diagnosed with PA but only a 3% risk of dying of it. The neoplasm is androgen dependent and does not occur in eunuchs. It is both more common and more aggressive in African-American men. PA must be differentiated diagnostically from benign prostatic hyperplasia, which is not a premalignant lesion. PA usually arises in the periphery of the gland and readily extends through the capsule into the periprostatic tissues, to seminal vesicles, and to regional lymph nodes. At the time of diagnosis, more than 40% of patients have disease that has spread beyond the gland. Bones of the axial skeleton are the usual sites of distant metastasis. The liver, lungs, and brain are other common sites. Early disease is asymptomatic; the diagnosis is most often made by screening of apparently healthy men with digital rectal examination, assay of prostate-specific antigen (PSA), or both. Advanced disease may present as urinary obstruction or bone pain due to metastasis. Men with nodular asymmetry or induration in the prostate gland on digital examination, or elevation of PSA, are evaluated by transrectal ultrasonography of the prostate with ultrasonically directed needle biopsy. Testing for osseous metastases includes measurement of serum alkaline phosphatase, radionuclide bone scan, computed tomography, and magnetic resonance imaging. PA is graded by the Gleason scoring method, which reflects the degree of histologic differentiation in the two most prominent malignant foci. Anatomic staging is based on extension of the tumor beyond the prostatic capsule, not on tumor size. A low or undetectable level of p27 protein in prostatic tissue is a marker of more aggressive malignancy. Treatment depends on the grade and stage of disease and the age and general condition of the patient. In elderly men and those with concurrent life-threatening illness, benign neglect may be the treatment of choice. Radical prostatectomy (removal of the entire gland along with the seminal vesicles) is generally reserved for patients with early or limited disease and a life expectancy of at least 10 years. This treatment is associated with a substantial risk of urinary incontinence and impotence. Radiotherapy with external beam radiation or transperineal implantation of radioactive isotopes may be employed besides or instead of surgery. Androgen blockade by orchidectomy or by administration of estrogen, an androgen antagonist, or a gonadotropin-releasing hormone is palliative in advanced disease. Some authorities oppose digital rectal examination and PSA screening of asymptomatic men with life expectancies of less than 10 years, on the grounds that the risks of false-negative results and of adverse consequences of aggressive treatment outweigh any possible benefit in survival or quality of life.