Evidence of Benefit
Before the 1990s, the digital rectal examination (DRE) was the test traditionally used for prostate cancer screening. Two other procedures are also available: transrectal ultrasound (TRUS) imaging and serum prostate-specific antigen (PSA) concentrations. Prostate cancer screening is controversial because of the lack of definitive evidence of benefit. A small randomized trial in Sweden evaluated the effects of screening men aged 50 to 69 years every 3 years; the first two screenings included DRE only, followed by two screenings with DRE combined with a test for PSA. The trial was not powered to detect even moderate differences in prostate cancer mortality, which was the same in the two groups: 1.3% (20 of 1,494 patients) for men assigned to screening and 1.3% (97 of 7,532 patients) for controls. The controversy persists. A nested case-control study was conducted at ten U.S. Department of Veterans Affairs (VA) medical centers in New England (71,661 patients receiving ambulatory care between 1989 and 1990), identifying 501 patients who were diagnosed with adenocarcinoma of the prostate from 1991 to 1995 and who died between 1991 and 1999. Controls were selected from among patients living at the time case patients died (matched 1:1 for age and VA facility). A benefit from screening by PSA or PSA and/or DRE was not found for PSA (odds ratio [OR], 1.08; 95% confidence interval [CI], 0.71-1.64; P = .72) or for PSA and/or DRE (OR, 1.13; 95% CI, 0.63-2.06; P = .68). Because prostate cancer has a relatively slow course, it is possible that the relatively short follow-up period in this study precluded the observation of a benefit, which might accrue only after 10 or more years from the time of screening.
Adding to the controversy is the lack of consensus regarding optimal treatment of localized disease and the clear evidence that active treatment options are associated with significant morbidity. Treatment options for early-stage disease include radical prostatectomy, definitive radiation therapy, and watchful waiting (no immediate treatment; treatment if indications of progression are present, but treatment not designed with curative intent). Multiple series from various years and institutions have been reported on the outcomes of patients with localized prostate cancer who received no treatment but were followed with surveillance alone. Outcomes have also been reported for active treatments, but valid comparisons of efficacy between surgery, radiation, and watchful waiting are seldom possible because of differences in reporting and selection factors in the various reported series. A randomized trial in Scandinavian men published in 2002 explored the benefit of radical prostatectomy over watchful waiting in men with newly diagnosed, well-differentiated, or moderately well-differentiated prostate cancers of clinical stages T1b, T1c, or T2. Six hundred ninety-eight men younger than 75 years, most with clinically detected rather than screen-detected cancers (unlike most newly diagnosed patients in North America) were randomly assigned to the two-arm trial. After 5 years of follow-up, the difference in prostate cancer-specific mortality between radical prostatectomy and watchful waiting groups was 2%; after 10 years of follow-up, the difference was 5.3% (relative risk [RR], 0.56 [0.36-0.88]). There was also a difference of about 5% in all-cause mortality that was apparent only after 10 years of follow-up (RR, 0.74 [0.56-0.99]). Thus 20 men with palpable, clinically localized prostate cancer would require radical prostatectomy rather than watchful waiting to extend the life of one man. Because most prostate cancers that are detected today with PSA screening are not palpable, this study may not be directly generalizable to the average newly diagnosed patient in the United States.