Population Screening for the Early ID of Prostate Cancer

Abstract & Commentary

By Jerome W. Yates, MD, Hematology/Immunology Unit, National Institute on Aging, NIH. Dr. Yates reports no financial relationships relevant to this field of study.

Synopsis: To assess whether screening for prostate cancer reduces prostate-specific mortality, a population-based, randomized, controlled trial for a random sample of men between the ages of 50 to 69 in a single city were screened every third year from 1987 to 1996. There was no significant difference in the rate of death from prostate cancer for the screened group compared to the control group after 20 years of follow-up.

Source: Sandblom G, et al. Randomised prostate cancer screening trial: 20 year follow-up. BMJ2011;342:1539-1545.

The use of prostate specific antigen (PSA) as a screening tool to identify men with cancer of the prostate gained momentum rapidly in the late 1980s. Its enthusiastic acceptance as a suitable test for identifying early prostate cancer rapidly gained acceptance among members of the urological community because elevations (> 4 ug/L) led to prostate biopsies that often found localized prostate cancer. The benefit of a prostate cancer screening program has yet to be demonstrated in a randomized clinical trial in which fewer prostate cancer deaths are observed among those screened.1

Examining the relative success of screening, diagnostic, and treatment programs for prostate cancer is complicated. Problems with "minimal risk disease" characterized by low-volume tumors with low Gleason scores and little chance of causing death provides a major challenge.2 Based on an autopsy series of men, subclinical or latent prostate cancer appears as early as the second decade of life and increases linearly thereafter.3 A 70-year-old man undergoing prostate biopsy has nearly a 70% chance of yielding cancer. There also is a linear increase in mean tumor volume and an increasing Gleason score (measure of malignant potential) with age.3

In the current report, Sandblom and colleagues address the prostate cancer specific survival in both screened and not screened cohorts. They report that the risk ratio for death from prostate cancer in the screened group was 1.16 with the 95% confidence intervals extending from 0.78 to 1.73, clearly not statistically significant. Furthermore, there was no increase in prostate cancer survival for men for whom cancer was detected by screening.

Commentary

This is an important piece of work. Treatment with curative intent of minimal risk disease carries the same risk for complications as it does for those with more advanced disease. These complications include urinary incontinence, proctitis, and sexual impotence, any or all of which affect quality of life in a negative way. Unnecessary overtreatment is a serious problem that can result from population-based screening for prostate cancer.4

Because this article reflects the rigor of a population-based, randomized clinical trial with an impressive population sample, excellent compliance, a uniform intervention, and outstanding follow-up information providing outcome data, the conclusions are appropriate. The screened population had a slightly increased incidence of prostate cancer probably reflecting the detection of a larger number of indolent or minimal risk cancers. All men were managed in the same urological unit following their diagnosis for prostate cancer, minimizing the potential for treatment bias leading to a prostate cancer death differential between the screened and the control group.

Screening enthusiasts have done a great disservice to the medical community by using surrogate endpoints such as "down-staging" and increased survival (potentially the result of length bias — picking up slowly progressing disease and lead time bias, picking up disease earlier in its course without changing the overall course of the disease, or picking up indolent disease that will not progress). Physicians are stimulated by disease discovery, but it is clear that not all with elevated PSA or even histological changes consistent with a diagnosis of cancer will progress to clinically important disease. It is hoped that new molecular techniques will provide more precision in identifying truly "malignant" from indolent prostate cancer. Until then, PSA should not be recommended for population screening for prostate cancer.

Willet Whitmore, a urological surgeon, addressed the heart of the problem: "The quandary in prostate cancer: Is cure necessary in those for whom it is possible and is cure possible in those for whom it is necessary?"5 Some overtreatment may be necessary, but data from a variety of studies indicate population screening using PSA is not appropriate.

References

1. Kramer BS, et al. Prostate cancer screening: What we know and what we need to know. Ann Intern Med 1993;119: 914-923.

2. Dall'Era MA, et al. Active surveillance for early-stage prostate cancer: Review of the current literature. Cancer 2008;112:1650-1659.

3. Powell IJ, et al. Evidence supports a faster growth rate and/or earlier transformation to clinically significant prostate cancer in black than in white American men, and influences racial progression and mortality disparity. J Urol 2010;183:1792-1796.

4. Esserman L, et al. Rethinking screening for breast cancer and prostate cancer. JAMA 2009;302:1685-1692.

5. Montie JE, Smith JA. Whitmoreisms: Memorable quotes from Willet F. Whitmore, Jr, M.D. Urology 2004;63:207-209.