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

Diagnosis and Treatment by Clinical StateThe 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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Chapter 091. Benign and Malignant Diseases of the Prostate (Part 2) 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 andinvasive lesion localized to the prostate, to a metastatic lesion that results insymptoms and, ultimately, mortality from prostate cancer—can span decades.Management at all points is centered on competing risks that are defined byconsidering the disease as a series of clinical states (Fig. 91-1). The states aredefined operationally, on the basis of whether or not a cancer diagnosis has beenestablished and, for those already diagnosed, whether or not metastases aredetectable 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 stateuntil he has progressed. At each assessment, the decision to offer treatment and thespecific form of treatment is based on the risk posed by the cancer, relative tocompeting causes of mortality that may be present in that individual. It followsthat the more advanced the disease, the greater the need for treatment. For thosewithout a cancer diagnosis, the decision to undergo testing to detect a cancer isbased on the probability that a clinically significant cancer may be present. Forthose with a prostate cancer diagnosis, the clinical state model considers theprobability of developing symptoms or dying from disease. Thus, a patient withlocalized prostate cancer who has had all cancer removed surgically remains in thestate of localized disease as long as the PSA remains undetectable. The timewithin a state becomes a measure of the efficacy of an intervention, though theeffect may not be assessable for years. As many men with active cancer are not atrisk for developing metastases, symptoms, or death, the states model allows adistinction between cure—the elimination of all cancer cells, the primarytherapeutic objective when treating most cancers—and cancer control, in whichthe tempo of the illness is altered and symptoms controlled until the patient dies ofother causes. These can be equivalent therapeutically from a patient standpoint ifthe patient has not experienced symptoms of the disease or the treatment needed tocontrol it. Even when a recurrence is documented, immediate therapy is notalways necessary. Rather, as at the time of diagnosis, the need for intervention isbased 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 Prevention Several agents are under investigation for their potential to reduce the riskof clinically significant prostate cancer. Finasteride, a 5α-reductase inhibitor, hasbeen tested in men ages ≥55 years in the Prostate Cancer Prevention Trial, adouble-blind, randomized multicenter trial. The prostate cancer detection rate was18.4% (803 of 4364) in the finasteride group and 24.4% (1147 of 4692) in theplacebo group. Early concerns that the cancers detected in the finasteride groupwere high-grade [37% (280 of 757 cancers) vs. 22% (237 of 1068 cancers) for theplacebo group] have been shown to be an artifact of the reduced volume of themalignant epithelial cells in finasteride-treated patients. No effect on survival wasdetected. Vitamin E and selenium are also being tested as preventive agents (theSELECT study). Physical Examination The need to pursue a diagnosis of prostate cancer is based on symptoms, anabnormal DRE, or an elevated serum PSA. The urologic history should focus onsymptoms of outlet obstruction, continence, potency, or change in ejaculatorypattern. The DRE focuses on prostate size and consistency and abnormalities withinor beyond the gland. Many cancers occur in the peripheral zone and can bepalpated on DRE. Carcinomas are characteristically hard, nodular, and irregular,while induration may be due to benign prostatic hypertrophy (BPH) or to calculior 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 seminalcoagulum. It is produced by both nonmalignant and malignant epithelial cells.PSA is prostate-specific, not prostate cancer–specific, and serum PSA increasesmay occur from prostatitis, BPH, and prostate cancer. The performance of aprostate biopsy can increase PSA levels up to tenfold for 8–10 weeks. The serumPSA level is not affected by DRE. PSA circulates in the blood as an inactivecomplex with the protease inhibitors α1-antichymotrypsin and β2-macroglobulin,and it has an estimated half-life in serum of 2–3 days ...