PSA Screening: The Case in Favor

Although the US Preventive Services Task Force (USPSTF) position is nuanced, their decision to give prostate-specific antigen (PSA) screening a grade D recommendation has been widely interpreted by the public as a sign that screening should not be performed. Here, we put forth arguments for why PSA screening should be considered, and for whom.

The randomized data show that compared to no screening, screening can significantly reduce the risk of prostate cancer death, and the absolute benefit is highest for younger, healthier men with longer life expectancies. The European Randomized Screening Trial for Prostate Cancer (ERSPC) demonstrated a 21% relative reduction in prostate cancer–specific mortality among 162,388 men in the core 55–69 age group. When this trial was first reported in 2009 with a 9-year median follow-up, public enthusiasm for screening was dampened when it was learned that 1,410 men would need to be screened and 48 treated to save 1 life, which was commonly felt to be too high a burden.[1] These figures are misleading, however, because 1,410 and 48 were the numbers needed to screen and treat to save 1 life at 9 years, and this time horizon is far too short for the average 55-year-old man with a remaining life expectancy of over 25 years. In fact, after only 2 more years of follow-up, those numbers had dropped to 1,055 needing to be screened and 37 needing to be treated to save a life at 11 years, and a modeling study suggests that these numbers will continue to fall sharply as the time horizon is lengthened.[2]

The strongest data for the benefit of screening in younger, healthier men come from the 20,000-patient Swedish trial, which was unique because of the long follow-up (median, 14 years, compared with 11 years in the rest of the ERSPC trial), and because participants were generally younger (median age only 56, range 50–64).[3] In this study, the relative reduction in prostate cancer–specific mortality was a very strong 44%, and at 14 years only 293 men needed to be screened and 12 treated to save a 56-year-old man’s life. When deciding about screening for a 55-year-old with a life expectancy of 25 additional years, these are the numbers most appropriate to consider.

Skeptics of PSA screening will point to the negative results of the 76,693-person US Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer trial, which showed no difference in prostate cancer–specific mortality.[4] However, this trial was seriously harmed by prescreening and contamination. In the 3 years prior to enrollment, 44% of the men in both arms had already had a negative PSA screening, meaning that nearly half the men enrolled probably did not have prostate cancer and were highly unlikely to benefit from further screening during the subsequent 6 years of the trial. Furthermore, only 85% of men in the screening arm actually underwent annual PSA screening,[4] while 85% of men in the control arm reported undergoing PSA screening at least once before or during the trial. Interpreted accurately, the PLCO trial compared annually vs occasionally screening 85% of participants; these findings should thus not be taken as proof that PSA screening has no benefit.[5] Despite the problems with the PLCO trial, a post-hoc analysis found that men with minimal comorbidity had a significant 44% relative reduction in prostate cancer–specific mortality when randomized to screening[6]-a figure strikingly equivalent to the 44% reduction in prostate cancer–specific mortality seen in the generally young and healthy participants in the Swedish trial. Even with all its challenges, it was still possible to show from the PLCO data that healthier men derive a large prostate cancer–specific mortality benefit from screening.

When weighing these benefits against the hazards of screening, it is important to avoid conflating the harms of screening with the harms of overtreatment. Clearly it is a problem that 90% of men with low-risk prostate cancer still choose definitive treatment; however, the solution is not to avoid screening men who may significantly benefit from it, but rather to ensure that men are appropriately counseled after diagnosis. It is hoped that improved imaging and new molecular prognostic tests being developed will help prove to more men that they have indolent disease for which surveillance is a safe option.

Ultimately, the decision to screen should remain one that is arrived at through a shared decision making based on highly individualized discussions between physician and patient. In such a discussion, the facts presented about screening should be tailored to the patient’s exact situation, and the patient’s values should be used to guide the final decision. For younger, healthy men, PSA screening should continue to be strongly considered.

Disclosures:

The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320-8.

2. Loeb S, Vonesh EF, Metter EJ, et al. What is the true number needed to screen and treat to save a life with prostate-specific antigen testing? J Clin Oncol. 2011;29:464-7.

3. Hugosson J, Carlsson S, Aus G, et al. Mortality results from the Goteborg randomised population-based prostate-cancer screening trial. Lancet Oncol. 2010;11:725-32.

4. Andriole GL, Grubb RL, Buys SS, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310-9.

5. Pinsky PF, Blacka A, Kramer BS, et al. Assessing contamination and compliance in the prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Clin Trials. 2010;7:303-11.

6. Crawford ED, Grubb R, 3rd, Black A, et al. Comorbidity and mortality results from a randomized prostate cancer screening trial. J Clin Oncol. 2011;29:355-61.