Prostate Cancer
Prostate cancer is the second most common cause of cancer deaths in males, with about 30,000 deaths annually and more than 200,000 new cases per year in the United States. Lifetime risk estimates for diagnosis are approximately 18% for whites and 21% for blacks and the risk of death is close to 3% for whites and 5% for blacks. Since the 1991 peak, annual deaths from prostate cancer are down by 25%, corresponding closely to the introduction of prostate-specific antigen (PSA) screening and aggressive treatment. No clear etiologic factors have been identified, although a familial predisposition has been demonstrated, and an increased risk has been associated with some environmental factors such as cigarette smoking and a high-fat diet. A history of chronic prostatitis has been associated with a higher risk of prostate cancer in some studies. The median age at diagnosis is 68 years and it is rare in men under 50 years of age (<2% of cases).
The study of genetic influences on prostate cancer has resulted in three phenotypic classifications: sporadic, familial, and hereditary. Sporadic cancers account for most cases and occur in individuals with a negative family history. Familial prostate cancer (25%) refers to a man with more than one affected relative. Hereditary prostate cancer (HPC) (5%) refers to a family with three generations affected, or three first-degree relatives affected, or two relatives affected before age 55. HPC is marked by a pattern consistent with passage of a susceptibility gene via Mendelian inheritance. Early age at diagnosis is a recognized marker of genetic susceptibility for hereditary cancers.
Androgens clearly play a role in the development and maintenance of prostate cancer, which suggests that caution be taken in the use of androgen replacement regimens, especially in men with a familial or past history of prostate cancer.
PATHOLOGY
Greater than 95% of prostate cancers are acinar adenocarcinomas. Other infrequent types include ductal carcinomas and carcinosarcomas.
Ductal Carcinomas
Accounting for <5% of prostate cancers, ductal carcinomas include transitional and squamous cell carcinomas, intraductal adenocarcinoma and mixed ductal carcinomas, and endometrioid carcinomas. Patients commonly have hematuria, positive urinary cytologies, and normal PSA. Treatment is cystoprostatectomy if localized to the prostate. Metastases are generally osteolytic rather than osteoblastic, and most do not respond to androgen withdrawal; however, if elements of acinar adenocarcinoma are present, hormonal therapy may be beneficial.
Carcinosarcomas
These uncommon tumors contain various mesenchymal elements and have a poor prognosis. (The remainder of this discussion will concern only acinar adenocarcinoma of the prostate.)
Adenocarcinoma of the Prostate
Adenocarcinomas of the prostate arise primarily in the peripheral zone (70%); however, 20% arise in the transition zone and about 5% in the central zone and 85% of cases are multifocal. Histologically, it is characterized by architectural disturbance of glands, invasion of the intraprostatic perineural, lymphatic or vascular spaces, and cellular anaplasia.
Spread is by direct local extension and by lymphatic and vascular channels. Invasion of the capsule followed by extension to the seminal vesicles and bladder base indicates a more aggressive tumor. Ureteral obstruction occurs in 10% to 35% of patients with advanced disease. Direct extension to the rectum is rare. Lymphatic drainage is primarily to the obturator and hypogastric nodes. Osteoblastic bony metastasis is the most common location of distant spread, usually in the axial skeleton, such as the lumbar spine, proximal femur, pelvis, thoracic spine, ribs, sternum, and skull. Visceral metastases are commonest in the lung, liver, and adrenals.
Prostatic intraepithelial neoplasia is not cancer but rather it is histologically benign prostatic ducts lined by cytologically atypical cells. Only high-grade prostatic intraepithelial neoplasia (HGPIN) is of significance and is characterized by prominent nucleoli. HGPIN is found in up to 25% of initial biopsies and is associated with cancer being found in ˜25% of subsequent biopsies.
GLEASON’S GRADING SYSTEM
Gleason’s system uses five different histologic patterns (1-5) to characterize the degree of glandular differentiation under low-power magnification. It grades the two most representative areas of the tumor, called the primary and secondary grades, and adds those two values, giving a final Gleason’s score (also known as Gleason’s sum or combined Gleason’s grade) between 2 and 10. Cytologic features play no role in the grade of the tumor. A high Gleason’s score indicates increased dedifferentiation, increased risk of nodal metastases, and a more malignant potential. There is good correlation between Gleason’s sum and prognosis. Interobserver and intraobserver reproducibility is generally within one Gleason’s sum. The presence of Gleason’s pattern 4 or Gleason’s sum 7 or more tumors is predictive of a poor prognosis.
TNM STAGING SYSTEM
The clinical stage is an assessment of the extent of tumor based primarily on the digital rectal examination (DRE), PSA, and Gleason’s grade, in addition to any imaging modalities. The pathologic stage is based on histologic examination of the prostate and lymph nodes after surgical removal. The criteria most predictive of the prognosis are Gleason’s grade and pathologic stage, including the surgical margin status, presence of extracapsular disease, seminal vesicle invasion, and involvement of pelvic lymph nodes.
Nomograms have been developed for the prediction of pathologic stage based on the clinical T stage, PSA level, and Gleason’s score from needle biopsy specimens (Partin AW, et al. JAMA 1997;277:1445-1451). These tables have proved useful in counseling men with newly diagnosed prostate cancer about treatment alternatives.
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