PSA Screening Effective in Lowering Cancer-Related Mortality in Large Study

Investigators in Europe have confirmed the effectiveness of prostate-specific antigen screening in reducing the risk of cancer-related mortality and in detecting a larger share of prostate cancer cases.

On August 6, 2014, investigators Schröder et al published results of a 13-year follow-up study evaluating the effect of screening patients for prostate cancer using the prostate-specific antigen (PSA) test.¹

In the study, known as the European Randomised study of Screening for Prostate Cancer (ERSPC), investigators observed reductions in mortality from prostate cancer resulting from screening, updating the significant results found at 9 years and 11 years.¹

The core group of patients who received PSA testing during the study ranged from 55 years of age to 69 years of age, and resided in 8 countries across Europe. A group of patients who had not received PSA testing, with a broader age range at baseline evaluation (aged 50 to 74 years), were selected as the control group from population registry data.¹

Using an intent-to-treat analysis, investigators assessed the likelihood of mortality in the core group and performed a secondary analysis to correct for bias introduced by patients who dropped out of the study.¹

A total of 7408 patients developed prostate cancer in the intervention group and 6107 patients developed prostate cancer in the control group. The risk of developing prostate cancer was significantly greater in the control group (hazard ratio: 1.57 [95% CI: 1.51 to 1.62]), and the risk of death related to cancer was lower (hazard ratio: 0.79 [0.69-0.91]).¹

Although significant survival benefits and significant reductions in the risk of death were detected in patients undergoing PSA screening, the number of patients who need to undergo screening to prevent 1 additional case of prostate cancer is high, and the number needed to prevent 1 cancer-related death is even higher. Investigators estimated that, over 13 years, 1 additional case of prostate cancer would be detected for every 27 (95% CI: 17 to 66) patients tested, and 1 death due to cancer would be prevented for every 781 (95% CI: 490 to 1929) patients tested.¹

Investigators recognized the importance of quality of life considerations in the decision of whether or not to screen for prostate cancer using the PSA test. Using a simulation based on the 11-year data collected by the ERSPC group, investigators Heijnsdijk et al evaluated the gain in quality-adjusted life years (QALYs) through the PSA screening intervention.^1,2

Using the computer simulation model, Heijnsdijk et al determined that annual screening of men between the ages of 55 and 69 years would result in a total of 73 life years gained per 1000 men screened. By contrast, annual screening among men over a wider age range, between the ages of 55 and 74 years, would result in a total of 82 life years gained per 1000 men screened.²

Despite this benefit, the ERSPC found that the number of QALYs gained with annual screening of men between the ages of 55 and 69 years and men between the ages of 55 and 74 years would be identical in each group, with 56 QALYs gained in both populations.²

Reductions in quality of life may result from dysfunction of urinary control, bowel control, and sexual health, as well as the burden of annual screening. In addition, PSA screening may lead to overdiagnosis of prostate cancer in some cases. Investigators estimate that 43% of cancers diagnosed through PSA screening would never affect patients clinically over the patient’s lifetime.²

An additional factor is the psychological burden of elevated PSA screen results in the absence of prostate cancer. In a 2009 study, Schröder et al determined that 80% of elevated PSA levels would result in false-positive diagnoses of prostate cancer.^3,4

On the issue of PSA screening, the United States Preventive Services Task Force (USPSTF) has stated, “existing studies adequately demonstrate that the reduction in prostate cancer mortality after 10 to 14 years is, at most, very small even for men in what seems to be the optimal age range of 55 to 69 years. There is no apparent reduction in all-cause mortality.” The statement continues, “The USPSTF concludes that there is moderate certainty that the benefits of PSA-based screening for prostate cancer do not outweigh the harms.”⁴

Although PSA screening reduced the risk of cancer-related mortality and results remained robust after 13 years of follow-up in the ERSPC group, the USPSTF noted that results of studies carried out in the United States have not shown a mortality benefit of PSA screening. It was further noted that, in 5 countries involved in an earlier follow up of the ERSPC group analysis, no statistically significant benefit of PSA screening was proven. The 13-year follow-up of the ERSPC study is unlikely to alter the USPSTF’s decision regarding prostate cancer screening in the United States.⁴

References:

• Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet. 2014.
• Heijnsdijk EA, Wever EM, Auvinen A, et al. Quality-of-life effects of prostate-specific antigen screening. N Engl J Med. 2012;367(7):595-605.
• Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360(13):1320-1328.
• United States Preventive Services Task Force. Screening for Prostate Cancer U.S. Preventive Services Task Force Recommendation Statement. http://www.uspreventiveservicestaskforce.org/prostatecancerscreening/prostatefinalrs.htm. Published May 2012. Accessed August 2014.