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Reconsidering prostate cancer screening

In 2011, the US Preventive Services Task Force (USPSTF) issued its controversial draft recommendation against measuring prostate-specific antigen (PSA) in blood to screen for prostate cancer, claiming the test didn’t save lives. USPSTF is an independent panel of national experts convened by Congress to make evidence-based recommendations on preventive care. And the D grade that its members assigned to PSA screening regardless of a man’s age, race, or family history carried a lot of clout: since the recommendation was finalized in 2012, PSA screening by general practitioners has dropped by half, prostate biopsies are down by nearly a third, and radical prostatectomies have dropped by just over 16%.

New prostate cancer diagnoses are falling off accordingly. According to the American Cancer Society (ACS), incidence rates for early-stage prostate cancer fell by 25% between 2011 and 2013. ACS now predicts that new prostate cancer diagnoses will plummet by more than 47,000 cases in 2016, largely because fewer men than ever are being screened.

In 2017, USPSTF will issue a five-year update of its PSA screening guideline. Some experts predict the organization will soften its stance on the test. That’s because men diagnosed with low- and intermediate-risk prostate cancer are increasingly opting to have their tumors monitored rather than treated immediately. Through monitoring, men can avoid the incontinence and impotence that treatment might cause without sacrificing years of survival.

Active surveillance entails routine biopsies and checks whether PSA levels are rising. Kirsten Bibbins-Domingo, MD, PhD, professor of medicine and epidemiology at the University of California, San Francisco, chairs the task force. She said that when USPSTF issued its recommendation against PSA screening in 2012 (after recommending against it in men aged 75 years or older four years before), 80% of men who had PSA-detected lesions were being treated, even though many of them wouldn’t have benefited. Indeed, 1.3 million cases of prostate cancer were diagnosed in the United States between 1986 (when PSA testing was introduced) and 2009. Of them, more than a million were treated. “Too many men were experiencing harms from the diagnostic cascade,” Bibbins-Domingo said. “So it was challenging for us to recommend PSA screening. But if alterations in treatment patterns are now affecting the balance of benefits and harms, then we look forward to reviewing new evidence to see if a different approach is warranted.”

Otis Brawley, MD, chief medical officer at ACS, speculates that “since a diagnosis of prostate cancer in 2016 no longer means a man is definitely headed for radiation or radical prostatectomy, the task force will say that population harms associated with screening have decreased enough so that we can go from a grade of D, which discourages screening, to a grade of C, which recommends offering the test to selected men depending on their circumstances.”

Some welcome a return to PSA screening. Jim C. Hu, MD, professor of urologic oncology at Weill Cornell Medicine in New York, said that despite PSA’s shortcomings—including that PSA levels can go up when someone has some other kind of prostate problem, such as an enlarged prostate—“it’s the best thing we have in the absence of sticking your head in the sand and coming into the emergency room with bone pain, weight loss, and fatigue, which are the hallmarks of metastatic prostate cancer.”

Human prostate specific antigen (PSA/KLK3) with bound substrate from complex with antibody (PDB id: 2ZCK) by E A S. CC BY-SA 3.0 via Wikimedia Commons.

In justifying its position against PSA screening, USPSTF cited two major studies showing that the test wasn’t much of a lifesaver. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) launched in 1993 and randomized 76,693 US men to either routine PSA screening or usual medical care that may have included screening. Follow-up data reported in 2012 showed that routine screening did not affect survival, though some scientists criticized that finding because an excess of men in the control group were given PSA tests as part of usual medical care. The European Randomized Study of Screening for Prostate Cancer (the ProtecT trial) enrolled 182,160 men similarly offered routine screening or usual care that may have included screening. In that study, also published in 2012, screening reduced the risk of dying from prostate cancer by about 21%. However, researchers would have to screen 1,055 men with the PSA test and detect (and potentially treat) 37 cases to prevent one prostate cancer death.

“PSA screening will help a very few avoid a cancer death and lead many men to be overdiagnosed and treated unnecessarily—and many more to go through diagnostic evaluations that can hurt and scare them,” said H. Gilbert Welch, MD, MPH. “That’s why screening is a choice, not a public-health imperative.”

The wide adoption of active surveillance has put the balance of harms and benefits from PSA screening in a new light. In a study of 1,643 men published in 2016, men who chose monitoring were as likely to live ten years after being diagnosed with localized prostate cancer as men treated with radiation or radical prostatectomy. No difference in overall survival was apparent among the three groups. The authors emphasized that survival differences could emerge with longer follow-up.

Hu’s view is that if overtreatment is now less of a problem, the benefits from PSA testing become more apparent. “Is it really so bad to find out if you’re at increased risk and then to find out if you have prostate cancer? Knowledge in this case is empowering.” Hu also worried that declines in screening could reverse a substantial drop in prostate cancer mortality since the PSA test was adopted.

But Brawley said that no reliable evidence so far indicates that incidence rates for metastatic prostate cancer are climbing. According to researchers at Northwestern University Feinberg School of Medicine in Chicago, rates of metastatic prostate cancer increased by 72% between 2004 and 2013—a trend attributed partly to the drop in PSA screening. Brawley said the findings were statistically flawed because of “rookie errors” in epidemiology.

As far as alternatives to PSA screening, Brawley said none are ready for widespread use. “We all want to move away from the prostate biopsy [which has a roughly 3.5% infection rate] and to replace PSA with a more sophisticated screening test,” he said. “But even then we’d still have to consider this essential question: Does the test save lives? Too often that’s not the case.”

A version of this article originally appeared in the Journal of the Nation Cancer Institute.

Featured image credit: Medical Laboratory by DarkoStojanovic. CC0 Public Domain via Pixabay.

Recent Comments

  1. Chris O'Neill

    “In the European Randomized Study of Screening for Prostate Cancer, also published in 2012, screening reduced the risk of dying from prostate cancer by about 21%.”

    The ERSPC also claimed the 21% reduction was statistically significant, i.e. less than 2.5% chance that there is actually no prostate cancer mortality benefit in a randomly chosen group of men.

    Unfortunately, the statistical analysis by the ERSPC failed to account for the effect of clustering in its data, in which there is enormous variation in prostate cancer mortality benefit between the 7 countries in the ERSPC. If this variation is given an appropriate statistical analysis then it is likely that the prostate cancer mortality benefit is not statistically significant.

    This means that while it may be worth doing PSA screening (ignoring overall survival) in Sweden and the Netherlands with the way they treat men in those 2 countries, there is no significant prostate cancer survival benefit anywhere else. And this is before considering overall survival for which there has never been any significant benefit demonstrated even with flawed statistical analyses.

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