Two recent studies1,2 found that the rates of prostate-specific antigen (PSA) screening have declined since the U.S. Preventive Services Task Force (USPSTF) recommended against PSA screening in 2012. One of those studies additionally found that the incidence of early-stage prostate cancer also coincided with the 2012 PSA screening recommendation, and “alternative explanations for the substantial decrease in incidence between 2011 and 2012 are unlikely.”1 Although the studies are limited by short-term follow-up, the findings have raised concerns that the long-term results of reduced screening may be higher rates of metastatic prostate cancer and mortality.
Furthermore, major media, including The New York Times, The Washington Post, and The Wall Street Journal, have reported on the studies, often including comments from prostate cancer experts and warnings about the projected increased mortality. One of those often quoted in these reports was David F. Penson, MD, MPH, who wrote an editorial3 accompanying the two studies reported in The Journal of the American Medical Association. Dr. Penson is Professor and Chair, Department of Urologic Surgery, and Director, Center for Surgical Quality and Outcomes Research, at Vanderbilt University Medical Center, Nashville.
In a segment on National Public Radio, Dr. Penson called the decline in PSA testing “very disturbing.”4 Discussing the USPSTF 2012 recommendation with Reuters Health, Dr. Penson said an increase in advanced prostate cancers is “unfortunately what’s going to happen because of this recommendation.”5 Dr. Penson expanded on these and other themes in an interview with The ASCO Post.
Mortality Increase Unlikely Before 2022
“The first thing we are going to see is an increase in the number of men presenting with metastatic disease. Maybe that will be enough for people to rethink their positions, but it may not,” Dr. Penson said. “It may require, unfortunately, that people see an increase in mortality in order for them to say, maybe we shouldn’t have abandoned PSA screening completely. Maybe we should have thought of more targeted ways to screen, ways to minimize the harms and maximize the benefits of what is, frankly, an imperfect test.”
The study by Jemal et al1 estimated that 33,519 fewer cases of prostate cancer were detected in 2012 than in 2011 in men 50 years and older. Using an extrapolation formula developed for the European Randomized Study of Screening for Prostate Cancer (ERSPC) that after 13 years of follow-up, 27 additional prostate cancer cases needed to be detected among those screened to prevent 1 prostate cancer death, “would suggest that approximately 1,241 (33,519/27) more men will die of prostate cancer,” Dr. Penson wrote in the editorial. “This estimate may even be somewhat conservative,” he added. “Prostate-cancer mortality, when it occurs, happens long after diagnosis,” he noted. “Therefore, the increase in prostate cancer mortality rates associated with the 2012 decrease in PSA screening is unlikely to be detected for 7 to 10 years or later.”
Two Studies, Similar Findings
Both studies relied on self-reported responses to the National Health Interview Survey to determine PSA screening rates before and after the 2012 recommendations, although using different exclusion criteria and analyses resulted in slightly different study populations and results. The results are based on short-term follow-up, with screening rates last reported in 2013 and incidence rates reported in 2012. It should be noted, however, that the 2012 USPSTF recommendations were publicly announced in draft form in October 2011.
The study by Sammon et al2 included a total of 20,757 men, with 34% reporting screening in 2000 and 2005; 35%, in 2010; and 31%, in 2013. “After adjusting for patient factors, there were significant reductions in PSA screening associated with the 2012 USPSTF recommendations,” the authors noted.
The study by Jemal et al1 looked at screening rates for a total of 18,385 men 50 years and older who responded to the National Health Interview Survey. They found that the percentage of men who reported having been screened during the previous year was 36.9% in 2005, 40.6% in 2008, 37.8% in 2010, and 30.8% in 2013. “In relative terms,” according to the investigators, screening rates “decreased by 18%” between 2010 and 2013. Looking at prostate cancer incidence between 2005 and 2012, Jemal et al found “the largest year-over-year decline in incidence per 100,000 occurred between 2011 and 2012,” from 498.3 to 416.2—“an absolute decline of 82.1 cases per 100,000 men and a relative decline of 16%.”
Deploying PSA Testing More Effectively
“The PSA test is certainly imperfect, but perhaps,” Dr. Penson wrote in the editorial, “the PSA test can be deployed more effectively (or strategically), maximizing benefit while minimizing harm. For example, the American Urological Association’s Early Detection of Prostate Cancer guidelines suggest that a routine screening interval of 2 years or longer may be preferred over annual screening.” Those guidelines recommend offering PSA testing to men 55–69 years old.
“We have always been taught that we should be doing annual screening,” Dr. Penson told The ASCO Post, so the option of every-other-year PSA screening has not been really explored. “I think we need to start exploring it,” he added, “because to me, that is probably one possible solution. The solution is rather than saying no screening, or tons of screening, let’s figure out better ways to screen, and doing it every other year is a good first step.”
Other possible strategies are basing the frequency of PSA screening on a single initial measurement at a relatively young age (although that age has not been defined) and using nomograms to identify men at increased risk of prostate cancer. Although nomograms are widely available, they are not widely used. The reasons include lack of awareness and the perception that sitting down at the computer to use them “is going to slow down the doctor-patient interaction,” Dr. Penson said. “But the reality is nomograms are of value. The Prostate Cancer Prevention Trial risk calculator will show patients the risk of whether or not they have a clinically meaningful cancer,” he added, and will help them to decide whether or not to have a biopsy or to follow a more targeted screening strategy.
The Potential of Biomarkers
The Stockholm 3 (STHLM3) study, recently reported in The Lancet Oncology, found that using a combination of plasma protein biomarkers (including PSA), genetic polymorphisms, and clinical variables (age, family history, previous prostate biopsy, prostate exam) “performed significantly better than PSA alone for detection of cancers with a Gleason score of at least 7.”6 The STHLM3 model “could reduce unnecessary biopsies” and “could be a step toward personalized risk–based prostate cancer diagnosis programs,” the investigators stated.
“We need to develop more data to see if that particular set of biomarkers is helpful,” Dr. Penson explained. “There are other tests out there as well, where we have preliminary data: the 4K Score and the Prostate Cancer Index (PHI). We have to start looking in greater detail at these biomarkers and see if they actually improve our ability to detect clinically meaningful prostate cancer and make an intervention.”
‘Reconsider Their Position’
Dr. Penson said that he would like to see the members of the USPSTF “reconsider their position” on prostate cancer screening. “I am not saying that annual PSA screening is something that deserves a grade A or grade B recommendation, because the evidence doesn’t support that,” he noted. (Both grades A and B indicate that the USPSTF recommends the service and practitioners should offer or provide it, but grade A confers a higher certainty of benefit.) However, he continued, the evidence “doesn’t necessarily support a grade D,” which is the current grade given by the USPSTF, “or even a grade C recommendation. (Grade D means that the USPSTF recommends against the service because of a moderate to high certainty that the service has no real benefit. For grade C recommendations, “there is at least moderate certainty that the net benefit is small,” and the USPSTF recommends selectively offering or providing the services to individuals based on professional judgment and patient preference.)
Studies “show that in some men, there is benefit to screening,” Dr. Penson said. “The rate of overtreatment has dropped considerably in the past 5 to 10 years. So hopefully,” he added, USPSTF members “will take that into account. There is real justification for them to rethink their recommendation and to consider being a little bit less extremist about it.”
In fact, the USPSTF prostate cancer screening recommendation “is in the process of being updated,” according to information on the Task Force’s website. Draft research is available at www.uspreventiveservicestaskforce.org.
A Swinging Pendulum
The current recommendation against prostate cancer screening may represent a swinging of the pendulum after 2 decades of an “overly aggressive” approach to screening and treatment, Dr. Penson noted. He encourages reaching a consensus about prostate cancer– screening strategies “and ultimately helping men by stopping the swinging pendulum somewhere in the middle.”
Just where that middle might or should be is difficult to determine, admitted Dr. Penson. “We need more research to figure out what is the best way to screen. But I am certain of two things,” he said: “to do no screening at all is wrong, and to do population-wide screening on an annual basis is also wrong.
The right way may be somewhere between these polar opposites, Dr. Penson revealed. “Maybe it is every other year screening. Maybe it is personalized screening strategies based on a baseline PSA and other risk factors or a nomogram. There are a number of different ways we can spin this. But it is somewhere in there.”
The ASCO Post asked Dr. Penson that if consensus is not reached, does he think it will take rising mortality rates to swing the pendulum back the other way? “Unfortunately, I do,” he answered. “Given the way the two sides have dug in, and the fact that we are dealing with so much emotion and rhetoric, I think we are going to have to see some real hard changes in the way prostate cancer presents and the outcomes associated with it for people to realize that we need to sit back down at the table and think this out.” ■
Disclosure: Dr. Penson has received research support from Astellas, Medivation, AHRQ, and PCORI.
References
1. Jemal A, Fedewa SA, Ma J, et al: Prostate cancer incidence and PSA testing patterns in relation to USPSTF screening recommendations. JAMA 314:2054-2061, 2015.
2. Sammon JD, Abdollah F, Choueiri TK, et al: Prostate-specific-antigen screening after 2012 US Preventive Services Task Force recommendations. JAMA 314:2077-2079, 2015.
3. Penson DF: The pendulum of prostate cancer screening. JAMA 314:2031-2033, 2015.
4. Stein R: Prostate cancer screening drops sharply, and so do cancer cancers. National Public Radio, November 18, 2015. Available at http://www.npr.org/sections/health-shots/2015/11/17/456201282/prostate-screening-drops-sharply-and-so-do-cancer-cases. Accessed December 10, 2015.
5. Seaman AM: Prostate cancer screening, early cases, in decline. Reuters Health, November 17, 2015. Available at http://mobile.reuters.com/article/healthNews/idUSKCN0T620M20151117. Accessed December 10, 2015.
6. Grönberg H, Adolfsson J, Aly M, et al: Prostate cancer screening in men aged 50-69 years (STHLM3): A prospective population-based diagnostic study. Lancet Oncol. November 9, 2015 (early release online).
