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Chapter 091. Benign and Malignant Diseases of the Prostate (Part 2)

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Diagnosis and Treatment by Clinical State The disease continuum—from the appearance of a preneoplastic and invasive lesion localized to the prostate, to a metastatic lesion that results in symptoms and, ultimately, mortality from prostate cancer—can span decades. Management at all points is centered on competing risks that are defined by considering the disease as a series of clinical states (Fig. 91-1). The states are defined operationally, on the basis of whether or not a cancer diagnosis has been established and, for those already diagnosed, whether or not metastases are detectable on imaging studies and the measured level of testosterone in...

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  1. Chapter 091. Benign and Malignant Diseases of the Prostate (Part 2) Diagnosis and Treatment by Clinical State The disease continuum—from the appearance of a preneoplastic and invasive lesion localized to the prostate, to a metastatic lesion that results in symptoms and, ultimately, mortality from prostate cancer—can span decades. Management at all points is centered on competing risks that are defined by considering the disease as a series of clinical states (Fig. 91-1). The states are defined operationally, on the basis of whether or not a cancer diagnosis has been established and, for those already diagnosed, whether or not metastases are detectable on imaging studies and the measured level of testosterone in the blood. With this approach, an individual resides in only one state and remains in that state until he has progressed. At each assessment, the decision to offer treatment and the specific form of treatment is based on the risk posed by the cancer, relative to
  2. competing causes of mortality that may be present in that individual. It follows that the more advanced the disease, the greater the need for treatment. For those without a cancer diagnosis, the decision to undergo testing to detect a cancer is based on the probability that a clinically significant cancer may be present. For those with a prostate cancer diagnosis, the clinical state model considers the probability of developing symptoms or dying from disease. Thus, a patient with localized prostate cancer who has had all cancer removed surgically remains in the state of localized disease as long as the PSA remains undetectable. The time within a state becomes a measure of the efficacy of an intervention, though the effect may not be assessable for years. As many men with active cancer are not at risk for developing metastases, symptoms, or death, the states model allows a distinction between cure—the elimination of all cancer cells, the primary therapeutic objective when treating most cancers—and cancer control, in which the tempo of the illness is altered and symptoms controlled until the patient dies of other causes. These can be equivalent therapeutically from a patient standpoint if the patient has not experienced symptoms of the disease or the treatment needed to control it. Even when a recurrence is documented, immediate therapy is not always necessary. Rather, as at the time of diagnosis, the need for intervention is based on the tempo of the illness as it unfolds in the individual, relative to the risk- to-benefit ratio of the therapy being considered. No Cancer Diagnosis
  3. Prevention Several agents are under investigation for their potential to reduce the risk of clinically significant prostate cancer. Finasteride, a 5α-reductase inhibitor, has been tested in men ages ≥55 years in the Prostate Cancer Prevention Trial, a double-blind, randomized multicenter trial. The prostate cancer detection rate was 18.4% (803 of 4364) in the finasteride group and 24.4% (1147 of 4692) in the placebo group. Early concerns that the cancers detected in the finasteride group were high-grade [37% (280 of 757 cancers) vs. 22% (237 of 1068 cancers) for the placebo group] have been shown to be an artifact of the reduced volume of the malignant epithelial cells in finasteride-treated patients. No effect on survival was detected. Vitamin E and selenium are also being tested as preventive agents (the SELECT study). Physical Examination The need to pursue a diagnosis of prostate cancer is based on symptoms, an abnormal DRE, or an elevated serum PSA. The urologic history should focus on symptoms of outlet obstruction, continence, potency, or change in ejaculatory pattern. The DRE focuses on prostate size and consistency and abnormalities within or beyond the gland. Many cancers occur in the peripheral zone and can be palpated on DRE. Carcinomas are characteristically hard, nodular, and irregular,
  4. while induration may be due to benign prostatic hypertrophy (BPH) or to calculi or tumor. Overall, 20–25% of men with an abnormal DRE have cancer. Prostate-Specific Antigen PSA is a kallikrein-like serine protease that causes liquefaction of seminal coagulum. It is produced by both nonmalignant and malignant epithelial cells. PSA is prostate-specific, not prostate cancer–specific, and serum PSA increases may occur from prostatitis, BPH, and prostate cancer. The performance of a prostate biopsy can increase PSA levels up to tenfold for 8–10 weeks. The serum PSA level is not affected by DRE. PSA circulates in the blood as an inactive complex with the protease inhibitors α1-antichymotrypsin and β2-macroglobulin, and it has an estimated half-life in serum of 2–3 days. Levels should be undetectable if the prostate has been removed. Immunohistochemical staining for PSA can be used to establish a prostate cancer diagnosis. PSA testing was approved in 1994 for early detection of prostate cancer, but there is controversy on its use. The American Cancer Society recommends that physicians offer PSA testing and a DRE on an annual basis for men over age 50 with an anticipated survival of >10 years; this includes men up to age 76 years. For African Americans and men with a family history of prostate cancer, testing is advised to begin at age 45. The American Urologic Association recommendations are similar, with a proviso that the risks and benefits of the performance of these
  5. tests are not defined. The National Comprehensive Cancer Network advises testing at age 40, tailoring additional testing to the age-specific median. The American College of Physicians recommends that physicians "describe the potential benefits and known harms of screening" and to "individualize the decision to screen." PSA values may fluctuate for no apparent reason; thus, an isolated abnormal value should be confirmed before proceeding with further testing.
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