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Screening for Prostate Cancer: A Double-Edged Sword
Abstract & commentary
By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips serves on the speakers bureaus for Cephalon, Resmed, and Respironics.
Synopsis: In a large, randomized, controlled trial, screening for prostate cancer did not have a significant effect on mortality from prostate cancer after 20 years of follow-up.
Source: Sandblom G, et al. Randomised prostate cancer screening trial: 20 year follow-up. BMJ 2011;342:d1539.
This report comes from the prestigious Swedish South-east Region Prostate Cancer Register. For this report, 1494 men from the original cohort were randomized to be screened every third year for prostate cancer and the 7532 remaining men were the control group. The first screening of the annual screening sessions took place in 1987. During this screening, both a specialist in urology and a general practitioner performed digital rectal examinations. Because the findings between the specialists and generalists were similar, subsequent examinations were undertaken by general practitioners. In 1993 and 1996, the digital rectal examination was combined with a test for prostate-specific antigen (PSA), with concentrations of > 4 µg/L as the cutoff. When the results of the digital rectal examination or PSA led to a suspicion of prostate cancer, the men underwent fine-needle aspiration biopsy. Men with positive cytologies were followed up and treated by a urologist. The participants in this study were followed until 2008, a period of 20 years. Over the period of follow-up, 85 cases (5.7%) of prostate cancer were diagnosed in the screened group and 292 (3.9%) in the control group. The percentage of men with localized tumors was significantly higher in the screened group (56.5%) than in the control group (26.7%, P < 0.001). The rates of non-localized tumors were similar in the screening group (2.5%) and in the control group (2.8%). The prostate cancer specific mortality was 30 out of 85 (35%) for men with prostate cancer diagnosed in the screening group and 130 out of 292 (45%) for men with prostate cancer diagnosed in the control group, but the overall mortality for men with prostate cancer was 81% in the screening group and 86% in the control group. The median cancer-specific survival was 201 months in the screened group and 133 months in the control group. In this large cohort, there was neither a significantly longer prostate cancer survival (P = 0.065) or overall survival (P = 0.14) for men with prostate cancer diagnosed in the screening group compared with the observed group.
How, when, and whether to screen asymptomatic men for prostate cancer remains unknown. The current study advances the data on screening for prostate cancer detection because it had high rates of compliance, uniform treatment, and complete data on tumor stage, tumor grade, and cause of death. In addition, routine screening for prostate cancer in Sweden has been relatively uncommon, reducing the risk that the trial is undercut by screening as part of clinical care in the control group.
Two recently completed trials, The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial1 and the European Randomized Study of Screening for Prostate Cancer2 (ERSPC), failed to show unequivocal benefit from PSA screening. The ERSPC trial showed a significant improvement in cancer-specific survival for men in the screened group, but there was a high rate of overdiagnosis and overtreatment. On the other hand, the PLCO trial did not show any benefit from screening, perhaps because of a short follow-up and because many of those in the control group may have undergone screening as part of routine care. In their discussion, the authors of the current Swedish study note that the results of their study, as well as the PLCO and ERSPC studies, indicate that there is a high rate of overdiagnosis in prostate cancer screening and this has to be weighed against any benefits of such screening. The ERSPC trial estimated that screening for prostate cancer could result in much earlier detection of prostate cancer, but 1410 men would need to be screened and 48 treated to prevent one death from cancer. Taken together, these trials suggest that screening may detect prostate cancer at an earlier stage, but there are significant issues with false positives and extra testing.
A key question then becomes whether earlier detection affects important outcomes (death is a biggie in this regard). In a recent report from Johns Hopkins,3 where carefully selected men with early prostate cancer are being managed with "active surveillance" (as opposed to intervention with curative intent), there have been no prostate cancer deaths after an average follow-up of about 6½ years. The authors suggest that watchful waiting may be safe for carefully selected men.
What does this mean to us when counseling our male patients about routine PSA screening for prostate cancer? The authors of the current study suggest that asymptomatic men should be informed about the potential hazards of treatment with curative intent before they undergo PSA screening. These risks include erectile dysfunction, urinary incontinence, and bowel symptoms. Health care consumers in the United States are almost certainly more obsessed with screening tests than are our European counterparts. But this recommendation seems very sound to me.
1. Andriole GL, et al for the PLCO Project Team. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009;360:1310-1319.
2. Schröder FH, et al. ERSPC Investigators. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360:1320-1328.
3. Tosoian JJ, et al. Active surveillance program for prostate cancer: An update of the Johns Hopkins experience. J Clin Oncol 2011 Apr 4. [Epub ahead of print]