March 31, 2009

Questions Remain About Benefit of PSA Screening for Prostate Cancer


Two randomized studies of prostate-specific antigen (PSA) screening for prostate cancer were recently published in the New England Journal of Medicine. One of the studies, conducted in Europe, reported that PSA screening decreased prostate cancer mortality by 20%. The other study, conducted in the United States, found that higher levels of PSA screening did not influence prostate cancer mortality. 

An estimated one in six men in the U.S. will be diagnosed with prostate cancer over the course of his lifetime. Prostate cancer occurs more frequently in older men, in African-American men, and in men with a family history of prostate cancer.

Men 50 years of age or older in the United States are often offered prostate-specific antigen (PSA) testing for the early detection of prostate cancer. The PSA test measures proteins that are produced and shed by the prostate. PSA levels tend to be elevated when prostate cancer is present, but levels can also be elevated in benign (non-cancerous) conditions affecting the prostate.

Although PSA screening is common in the United States, there has been no conclusive evidence that it reduces the risk of death from prostate cancer. Furthermore, there are potential risks of screening. The main argument against PSA screening is that it may lead to the diagnosis and treatment of cancers that would not have been discovered or caused problems during the life of the man being screened. This is referred to as “overdiagnosis.” The diagnosis and treatment of these nonfatal cancers causes significant morbidity and interferes with a good quality of life. There are also economic consequences of overdiagnosis in that a large number of patients need to be diagnosed and treated for each patient saved by early diagnosis. Part of the problem is that physicians are not able to distinguish accurately between prostate cancers that are aggressive and likely to kill and those that are unlikely to be lethal.

To explore the risks and benefits of PSA screening, researchers in Europe and the United States conducted large randomized studies:

The European Randomized Study of Screening for Prostate Cancer involved 182,000 men ages 50-74 from seven European countries.[1] The men were randomly assigned to be screened with a PSA test once every four years or to not receive this screening (control group). A PSA level of 3 ng per millimeter was considered abnormal and prompted a biopsy (except in Finland where the threshold PSA was 4 ng per millimeter, as in the U.S. study). Study participants have now been followed for a median of nine years.

  • Risk of death from prostate cancer was 20% lower among men assigned to the screening group than among men assigned to the control group.
  • The researchers estimated that 1,410 men would need to be screened and 48 would need to be treated for prostate cancer in order to prevent one death from prostate cancer.

The researchers concluded that PSA screening reduced the risk of death from prostate cancer but at the cost of substantial overdiagnosis.

The U.S. Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial involved 76,693 men.[2] Men in the screened group had annual PSA testing for six years and digital rectal exam for four years. Men in the control group were allowed “usual” care, and many received PSA testing (rates of PSA testing in the control group increased from 40% in the first year of the study to 52% in the sixth year of the study).  Because so many men in the control group were screened, this study wasn’t a true comparison of screening versus no screening. Instead, it compared a group with higher levels of screening to a group with lower levels of screening.

The threshold PSA level for biopsy was 4 ng per millimeter.

  • After 7 to 10 years of follow-up, rates of death from prostate cancer were low, and there were no statistically significant differences in risk of death between the study groups.

Although this study suggests that higher levels of PSA screening do not decrease the risk of death from prostate cancer, the researchers note that follow-up is ongoing and final results are not yet available.

What do the results of these two studies mean for men? An editorial that accompanies the studies notes that “Serial PSA screening has at best a modest effect on prostate-cancer mortality during the first decade of follow-up. This benefit comes at the cost of substantial overdiagnosis and overtreatment.”[3] Because the balance of potential risks and benefits is likely to be perceived differently by different people, the editorial goes on to state “…a shared decision-making approach to PSA screening, as recommended by most guidelines, seems more appropriate than ever.”

Men who are considering PSA testing are advised to discuss the potential risks and benefits with their physician.


[1] Andriole GL, Grubb RL, Buys SS et al. Mortality results from a randomized prostate-cancer screening trial. New England Journal of Medicine. 2009;360:1310-9.

[2] Schröder FH, Hugosson J, Roobol MJ et al. Screening and prostate-cancer mortality in a randomized European study. New England Journal of Medicine. 2009;360:1320-8.

[3] Barry MJ. Screening for prostate cancer: the controversy that refuses to die. New England Journal of Medicine. 2009;360:1351-4.

Copyright © 2010 CancerConsultants Prostate Cancer Information Center. All Rights Reserved.

Tags: Prostate Cancer, Uncategorized