Even now, after 25 years, "there is still no clarity about the usefulness and desirability" of routine screening for prostate cancer using the prostate-specific antigen (PSA) blood test, experts comment in a "sounding board" article published March 30 in the New England Journal of Medicine.
The authors, headed by Paul F. Pinsky, PhD, are from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
They point out that the data from two large trials of PSA screening ― the European Randomized Study of Screening for Prostate Cancer(ERSPC), and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) ― suggest that "net benefit is unlikely to be more than marginal, whereas the harms are proven and substantial."
"Under the 'first do no harm' principle, it seems reasonable to forgo mass screening as a public health policy at this point, but to continue to perform research on how to reduce the harms of PSA screening while maintaining any benefits," they write.
Mass screening is now discourage – in 2012, the US Preventive Services Task Force (USPSTF) recommended against routine PSA-based screening for healthy men regardless of age.
That recommendation set off a frenzy of discussion and discord.
A number of organizations and professional societies issued their own guidelines that either recommended against PSA-based screening for average-risk men or recommended some type of shared decision making about screening, the authors note. As an example, the American College of Physicians recommends discussing the benefits and harms of screening and ordering screening only when the patient expresses a clear preference for it.
Making Sense of the Data
Making sense of the data is complex, Dr Pinksy and colleagues comment. Both the PLCO and ERSPC were difficult undertakings, and "neither trial is devoid of flaws," they note. Non-PLCO researchers have investigated a problem with contamination in the PLCO, and a question was raised about the ERSPC regarding an imbalance in treatments across groups, even after accounting for cancer stage.
But all things considered, on the basis of available evidence, it is estimated that approximately 1 prostate cancer death is averted per 1000 men who each undergo screening several times and are followed for 10 to 15 years, Dr Pinsky and colleagues explain.
But establishing whether there is any benefit associated with PSA screening is only one side of the equation, they point out. Harms associated with treating prostate cancer are common. The recommendations against screening are based on the conclusion that the harms may outweigh any likely benefits.
As with other screening tests, they note, the "downstream sequelae" from a false positive ranges from anxiety to an unneeded biopsy. But what "distinguishes PSA testing among cancer screening tests with respect to harms is the extent of overdiagnosis of indolent, nonlethal cancers combined with the frequency and severity of side effects from the standard therapies used to treat such cancers."
"Pseudoepidemic" of Prostate Cancer Diagnoses
Screening has created a "pseudoepidemic" of prostate cancer diagnoses, with incidence rising from approximately 135 per 100,000 at the advent of the screening era in 1987 to a mean of 220 in the period 1991 through 1993 (a 63% increase). This trend continued, with well above 150 per 100,000 through 2009, they add.
The authors also point to the declining incidence of prostate cancer, which coincides with the drop in PSA testing rates since the release of the USPSTF guidelines. From 2010 to 2013, screening rates decreased from 33.2% to 24.8% for men aged 50 to 59 years, and the drop was even greater for men aged 60 to 74 years, from 51.2% to 43.6%.
During the same period, data from the Surveillance, Epidemiology, and End Results program show a gradual decline in incidence of prostate cancer of approximately 23% from 2001 to 2011, followed by a more precipitous 20% decrease in 1 year from 2011 to 2012, and then another small decrease (6%) from 2012 to 2013.
What has happened in the United States constitutes a "natural experiment" that reflects population-level changes in PSA screening patterns, the authors comment. "Because of various gaps and delays in obtaining critical data, however, as well as the extended time it takes for prostate tumors to progress, the challenge is to analyze the results of this experiment in terms of the effect of these changes on prostate cancer mortality as quickly and accurately as possible," they write.
So the question is, where to go next with PSA screening to make use of its benefits but reduce associated harms. Some suggestions, they note, are to screen less frequently or not at all for men with very low PSA values.
Active monitoring could reduce overtreatment, but drawbacks of this approach include required periodic biopsies and anxiety from delaying treatment, the authors continue.
"There is a critical need for strategies to reduce the burdens associated with the diagnosis of indolent disease, through a combination of not diagnosing it in the first place and accurately classifying it as not needing any further follow-up or treatment, while still maintaining any mortality benefits for men with aggressive disease. Perhaps that is the most pressing research challenge going forward," they conclude.
The authors have disclosed no relevant financial relationships.