In 2009, early results from two major studies regarding prostate cancer screening were released in the New England Journal of Medicine. In these studies, a total of more than 250,000 men were randomized to screening and followed for prostate cancer death.
These studies have formed the basis for most prostate cancer screening recommendations, yet they are commonly misunderstood. To better assess the implications of these studies, it's important to review study design, strengths and weaknesses in order to place them in context within the larger debate on prostate cancer screening.
The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, a study based in the United States, randomized 76,693 men ages 55 to 74 to either annual screening with PSA and digital rectal examination or usual care.
In this study, approximately 17 percent more cancers were detected in the screening arm than in the control arm, but there was no difference in cancer-specific death.
Although technically randomized, a criticism of the study is that it doesn't appear to have been particularly well controlled:
These data call into question the reliability of the study's findings — the screening and control groups essentially blended together, reducing the study's ability to detect a difference between the two groups.
The European Randomized Study of Screening for Prostate Cancer (ERSPC) trial was a randomized screening study based in Europe. In this study:
ERSPC suffers from fewer of the limitations of PLCO. Specifically, very few men were screened prior to entry into the study and contamination of the control group was significantly lower at 15 percent. Compliance with biopsy recommendation was also much higher at 85 percent.
ERSPC has been criticized for lack of informed consent in many of the countries, however, and many more screened men opted for active surveillance in ERSPC than in PLCO (18 percent vs. 11 percent).
Finally, although there was a significant benefit to screening, nearly 1,400 men needed to be screened and 48 men treated to save one life after eight years. It should be noted, though, that with longer follow-up and further prostate cancer-related deaths, the number of men needed to be screened and treated to prevent one death will very likely decrease.
While ERSPC and PLCO both had similar endpoints and objectives, the manner in which the studies were performed and their interpretation were widely divergent. Nonetheless, there are important, complementary data that emerged from both trials:
The diversity of methodology and data from these trials allows for significant flexibility in their interpretation, which makes it difficult to use them to substantiate across-the-board recommendations. Rather, the decision of whether to screen or not screen — using PSA testing or other means or both — is a decision best made between physicians and their individual patients.
"In making this decision, both physicians and their patients should be informed of the benefits and risks of screening or not screening. Other clinical factors, such as age, comorbidities, 10-year life expectancy and patient preferences, should also be taken into account. By being fully informed, patients and physicians are better armed to combat prostate cancer," says Erik P. Castle, M.D., a urologic surgeon at Mayo Clinic in Arizona.
Andriole GL, et al. Mortality results from a randomized prostate-cancer screening trial. New England Journal of Medicine. 2009;360:1310.
Andriole GL, et al. Prostate cancer screening in the randomized Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial: Mortality results after 13 years of follow-up. Journal of the National Cancer Institute. 2012;104:125.
Schroder FH, et al. Screening and prostate-cancer mortality in a randomized European study. New England Journal of Medicine. 2009;360:1320.