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INTRODUCTION

  • Prostate cancer is a malignant neoplasm that arises from the prostate gland. Prostate cancer has an indolent course; localized prostate cancer is curable by surgery or radiation therapy, but advanced prostate cancer is not yet curable.

PATHOPHYSIOLOGY

  • The normal prostate is composed of acinar secretory cells that are altered when invaded by cancer. The major pathologic cell type is adenocarcinoma (>95% of cases).

  • Prostate cancer can be graded. Well-differentiated tumors grow slowly, whereas poorly differentiated tumors grow rapidly and have a poor prognosis.

  • Metastatic spread can occur by local extension, lymphatic drainage, or hematogenous dissemination. Skeletal metastases from hematogenous spread are the most common sites of distant spread. The lung, liver, brain, and adrenal glands are the most common sites of visceral involvement, but these organs are not usually involved initially.

  • Hormonal regulation of androgen synthesis is mediated through a series of biochemical interactions between the hypothalamus, pituitary, adrenal glands, and testes (Figure 64-1).

  • The testes and the adrenal glands are the major sources of androgens, specifically dihydrotestosterone (DHT).

  • Luteinizing hormone–releasing hormone (LHRH) from the hypothalamus stimulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gland.

  • LH complexes with receptors on the Leydig cell testicular membrane, stimulating the production of testosterone and small amounts of estrogen.

  • FSH acts on testicular Sertoli cells to promote maturation of LH receptors and produce an androgen-binding protein.

  • Circulating testosterone and estradiol influence the synthesis of LHRH, LH, and FSH by a negative-feedback loop at the hypothalamic and pituitary level.

FIGURE 64-1

Hormonal regulation of the prostate gland.

(ACTH, adrenocorticotropic hormone; DHT, dihydrotestosterone; FSH, follicle-stimulating hormone; GH, growth hormone; LH, luteinizing hormone; LHRH, luteinizing hormone–releasing hormone; mRNA, messenger RNA; PROL, prolactin; R, receptor.)

CHEMOPREVENTION

  • The use of 5-α-reductase inhibitors, finasteride and dutasteride, to prevent prostate cancer has been debated for more than a decade. Current guidelines do not recommend the use of these agents for prostate cancer chemoprevention.

SCREENING

  • Screening recommendations for prostate cancer have changed, and digital rectal examination (DRE) and prostate-specific antigen (PSA) are no longer recommended for patients without a discussion with their clinician about risks versus benefits. The American Urologic Association does not recommend routine screening in men between the ages of 40 and 54 years of average risk. They recommend that men aged 55–69 years discuss the risks and benefits of prostate cancer screening. Men who elect to have screening should do so no more than every 2 years; a recent study suggests that screening every 5 years may be adequate.

  • PSA is a glycoprotein produced and secreted by prostate epithelial cells. Acute urinary retention, acute prostatitis, and BPH influence PSA, thereby limiting the usefulness of PSA alone for early detection, but it is a ...

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