Prostate-specific antigen in the early detection of prostate cancer

Abstract

Throughout Canada, the United States and much of Europe, prostate-specific antigen (PSA) screening for prostate cancer has proliferated over the past 2 decades, leading to dramatic increases in detection rates of prostate cancer. Although it has unquestionably led to increased detection of cancer and a migration to lower-stage and -volume tumours, it is still unknown whether PSA screening significantly reduces mortality from prostate cancer. Often thought to be dichotomous (i.e., either normal or elevated), PSA measurements actually reflect cancer risk, with the risks of cancer and of aggressive cancer increasing with the level of PSA. The recently developed risk calculator from the Prostate Cancer Prevention Trial, which integrates family history of prostate cancer, digital rectal examination findings, PSA test result, age, ethnicity, and history of a prior prostate biopsy with a negative result, allows clinicians to assess a patient's individual risk of cancer. This risk should be examined in the context of a patient's life expectancy and comorbidity as well as his concern about the possibility of prostate cancer. The terms "normal" and "elevated" as descriptors of PSA results should be abandoned.

Fig. 1: Risk of prostate cancer by range of prostate-specific antigen level. Data are from control subjects involved in the Prostate Cancer Prevention Trial (N Engl J Med 2004;350:2239-46) who had normal digital rectal examination results and prostate-specific antigen levels < 4.0 ng/mL throughout the 7-year study, as well as an end-of-study biopsy (n = 2950). High-grade cancer refers to a Gleason score ≥ 7.

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Fig. 2: Micrographs of thin slices of prostate cancer tissue. Left, a mixture of two grade 3 patterns: Gleason grade 3+3 (a score of 6). Right, the most aggressive histologic pattern: Gleason score 10. Photo by: Dean A. Troyer, MD, Department of Pathology, University of Texas Health Science Center at San Antonio, Tex.

Fig. 3: Forest plot of risk factors for prostate cancer and for high-grade prostate cancer (Gleason score ≥ 7) if a prostate biopsy is performed. PSA = prostate-specific antigen, DRE = digital rectal examination.