Prostate Cancer Screening: Balancing Benefits and Harms

Selected by Pietro Cazzola

Cancro prostataSeveral large, prospective randomized trials have addressed the hypothesis that screening with PSA can reduce mortality for prostate cancer. The results to date remain controversial, and in 2012 the US Preventive Services Task Force recommended against PSA screening on the grounds that there is no net benefit and that the potential harms outweigh the benefits.1However, the Task Force’s conclusions have been criticized as premature in a rapidly evolving area of intensive research, including modeling studies that have showed, with a 4-year screening interval, a gain of 52 life-years and a gain of 41 quality of life–adjusted life-years were achieved per 100 men.2 Importantly, the reduction of quality-of-life in these analyses is primarily due to over-detection and long-term side effects of treatment.
The European Randomized study Screening for Prostate Cancer (ERSPC) is a multicenter, randomized trial initiated in 1993, which includes men between the ages of 50 and 74 years and which compared a screening interval of 4 years (2 years in Sweden) with a control group. In this updated analysis, the investigators report results of prostate cancer mortality based on follow-up to 13 years.3 Despite the longer follow-up, the results did not show a further increase in the relative effect of screening on prostate cancer mortality after 11 years. These findings suggest that 1 prostate cancer death is averted per 781 men screened, and an additional prostate cancer is detected in 1 per 27 men screened. The results were consistent across the entire age range using 5-year spans in age group. 
These estimations, which demonstrate a mortality benefit for screening, may improve with adjustments for noncompliance in the control group and longer follow-up. Although follow-up from randomization was 13 years, the median follow-up from diagnosis of prostate cancer was only 6.4 years in the screening cohort and 4.3 years in the control group; therefore, longer follow-up may result in further divergence in relative effect. Importantly, the study does not address over-detection and consequent harms of over-treatment. Although the time to recommend population-based screening has not yet arrived, physicians should consider applying PSA screening for men who desire it and provide them with balanced information during counseling. Improved adherence to active surveillance for low-risk tumors and incorporation of novel imaging technology to avoid prostate biopsy are required to favorably shift the ratio of benefits to harms.4 

References
  1. Moyer VA, U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157(2):120-134.

  2. 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.

  3. Schroder 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 [published online ahead of print August 6, 2014]. Lancet. doi:10.1016/S0140-6736(14)60525-0.

  4. Vickers A, Carlsson S, Laudone V, Lilja H. It ain't what you do, it's the way you do it: five golden rules for transforming prostate-specific antigen screening [published online ahead of print January 4, 2014]. Eur Urol. doi: 10.1016/j.eururo.2013.12.049.

 James A Eastham MD, Behfar Ehdaie MD, MPH