He began with a brief history of PSA testing and highlighted that this moved very quickly from its identification and use as a prostate cancer monitoring test to widely disseminated screening use.
Dr. Shelton highlighted two large randomized studies in the U.S. (Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial1) and Europe (European Randomized Study of Screening for Prostate Cancer (ERSPC)2) have been conducted to evaluate whether screening for prostate cancer using the PSA test improves overall and prostate cancer mortality.
He first focused on ERSPC, highlighting the 13-year follow-up data published in 2014. This shows that the relative reduction in prostate cancer death from PSA-based screening may be larger than previously estimated6. Based on these data, the absolute risk reduction in prostate cancer mortality from PSA screening was 0.11 per 1000 person or 1.28 per 1000 men randomized. This risk reduction has increased with increasing duration of follow up. Additional analysis has shown an absolute risk reduction of metastatic disease was 3.1 per 1000 men randomized7. In a subgroup of the ERSPC with longer follow-up, the absolute risk reduction in prostate cancer mortality was 4.0 per 1000 men randomized8. This corresponds to a number needed to screen of 293 and number needed to diagnose of 12 in order to prevent one prostate cancer death.
There are, however, issues with this trial which he highlighted. Some of these would under-estimate the benefit of screening (including non-compliance, contamination, and undertreatment of screen-detected cancer) and some would over-estimate the benefit of screening (lack of cause of death blinding).
He then discussed PLCO. This American based trial showed no benefit to PSA-screening. However, he highlighted issues with this trial, the most prominent of which were pre-enrollment PSA screening and ongoing contamination of the control arm. Thus, this trial represents an assessment of organized versus opportunistic screening.
He highlighted a number of potential opportunities for further assessment of this issue.
First, he highlighted modeling studies which account for the contamination and non-participation in both ERSPC and PLCO. Each of these studies demonstrated an even larger benefit to screening when these issues were accounted for. Additionally, healthier men were likely to derive a greater benefit from screening.
Additionally, men with high-risk disease were highlighted as deriving a greater benefit. Finally, he pointed out that, in addition to prostate cancer-related mortality, screening could reduce the incidence of prostate cancer metastasis and thus reduce the burden of treatment.
Thus, risk-based biopsy, using nomograms or risk calculators or using MRI, may allow maximization of the benefit of PSA screening.
Presented by: Jeremy Shelton, MD, Department of Urology, UCLA, Los Angeles, California
Written by: Christopher J.D. Wallis, Urology Resident, University of Toronto @WallisCJD at American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois
References:
1. Andriole GL, Crawford ED, Grubb RL, 3rd, et al. Mortality results from a randomized prostate-cancer screening trial. The New England journal of medicine 2009; 360(13): 1310-9.
2. Schroder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. The New England journal of medicine 2009; 360(13): 1320-8.
3. Moyer VA, Force USPST. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2012; 157(2): 120-34.
4. Gulati R, Tsodikov A, Wever EM, et al. The impact of PLCO control arm contamination on perceived PSA screening efficacy. Cancer Causes Control 2012; 23(6): 827-35.
5. Basch E, Oliver TK, Vickers A, et al. Screening for prostate cancer with prostate-specific antigen testing: American Society of Clinical Oncology Provisional Clinical Opinion. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2012; 30(24): 3020-5.
6. 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. Lancet 2014; 384(9959): 2027-35.
7. Schroder FH, Hugosson J, Carlsson S, et al. Screening for prostate cancer decreases the risk of developing metastatic disease: findings from the European Randomized Study of Screening for Prostate Cancer (ERSPC). European urology 2012; 62(5): 745-52.
8. Hugosson J, Carlsson S, Aus G, et al. Mortality results from the Goteborg randomised population-based prostate-cancer screening trial. The lancet oncology 2010; 11(8): 725-32.