鶹ýӰ

The Swinging Pendulum of PSA Screening

— Tide of opinion turning again

MedpageToday
A blue gloved hand holds a test tube labeled PSA TEST above a test form

In 2012, the U.S. Preventive Services Task Force (USPSTF) -- a powerful, voluntary group that sets guidelines for primary care physicians -- of healthy men with prostate-specific antigen (PSA) blood tests for the early detection of prostate cancer.

That statement, which was somewhat reversed in 2018, has lived on and continues to fuel hot debates over the use of screening and whether the guidelines themselves caused more harm than benefit. And there likely will be more arguments in the years ahead as medical groups conduct uptakes on guidelines and new studies appear.

It all started in 2012 when the USPSTF gave PSA screening a "D" grade, meaning it caused more harm than benefit. Groups such as the American Academy of Family Physicians (AAFP) and the American College of Physicians got on board. I took it to mean they were protecting men from overdiagnosis and overtreatment of prostate cancer, especially men like me with low-risk, low-volume prostate cancer.

The American Urologic Association (AUA) took the opposite view, arguing that early detection saves the lives of men with advanced prostate cancer.

David Penson, MD, MPH, a former guideline writer for the AUA and now Chair of the AUA's Public Policy Council, said the AUA and other urologic societies attacked the USPSTF's 2012 guidelines.

"The AUA felt the recommendation was wrong and did not account for the findings from the European trials specifically; it overvalued the American trial, and it didn't consider other endpoints. And so, at that point, we as an organization voiced our displeasure," said Penson, Chair of the Department of Urology at Vanderbilt University in Nashville. "We let the USPSTF know that we disagreed with their conclusions. We did speak to elected officials, but, of course, USPSTF is an independent entity, and they're entitled to make their recommendations. We were not included in the Task Force. And so, we were not part of that discussion."

USPSTF Chair Alex Krist, MD, MPH, a family medicine researcher at Virginia Commonwealth University in Richmond, stressed the independence of the Task Force, and noted that the group bases its recommendations solely on the scientific evidence. Krist also said that although the USPSTF has no urologist members, urologists were consulted in its reviews of PSA screening.

Prostate cancer patient Rick Davis, founder of AnCan, a platform for support groups for men with prostate cancer and other diseases, said the USPSTF in 2012 failed to make the distinction that a PSA could still provide information without necessitating treatment, instead discouraging all screening based on the D-rating.

"They blamed overtreatment on the PSA test rather than on the doctors who were misusing the information gathered and initiating procedures on men where they were not warranted. This of course would have required them to be critical of their colleagues and the medical profession," he said.

In response, Krist said that the USPSTF considered all potential benefits for the PSA test as a preventive service. However, he agreed with Davis's criticism that overtreatment could have been prevented if doctors used the PSA information more judiciously.

But, he added, "Back in 2012, the data actually showed that that's not what was being done."

"In fact, 90% of men with low-grade prostate cancers were getting surgery and radiation," said Krist. "And we know today that that is overtreatment, and the treatment patterns changed between 2012 and 2018 [when USPSTF again reviewed its PSA guidelines]."

The pendulum swung based on new research in 2018 as USPSTF and AAFP gave a slightly more acceptable C-grade to PSA screening based on new evidence.

In the Oct. 16 edition of Morbidity and Mortality Weekly Report, David Siegel, MD, of the CDC's Division of Cancer Prevention and Control at the National Center for Chronic Disease Prevention and Health Promotion, . He noted that the 2012 USPSTF recommendation "likely contributed to a decrease in overall reported prostate cancer incidence and might have contributed to an increase in the percentage and incidence of distant stage prostate cancer."

A study at Kaiser Permanente of Northern California demonstrated the problem in stark terms. While screening of the population of eligible men under the age of 70 grew from 404,000 to 524,000 at Kaiser, following the Task Force statement in 2012, screening rates declined 20.6%, biopsy rates declined 61.6%, and detection rates declined 48.3%, while metastatic rates increased 52%, according to Joseph C. Presti, Jr., MD, who .

Debate over routine screening for prostate cancer using PSA testing had occurred well before the FDA approved the test for prostate cancer screening in 1994. It has been a never-ending story of balancing the potential harms of overdiagnosing and overtreating men with prostate cancer lite versus providing necessary treatment to men with advanced prostate cancer.

In his 2014 book, The Great Prostate Hoax: How Big Medicine Hijacked the PSA Test and Caused a Public Health Disaster, Richard Ablin, PhD, of the University of Arizona College of Medicine, who discovered PSA in 1970, stressed that PSA testing was not intended for use for mass screening but rather to follow men with advanced disease. But after the FDA approval for screening, PSA testing was marketed to combine with the digital rectal exam (DRE) to detect prostate cancer early.

Thanks to PSA screening, prostate cancers were caught so early that the DRE was virtually unnecessary. DRE is considered a "lost art" among many primary care physicians and urologists, one not missed by many men.

Early detection no doubt helped men who were looking down the barrel of aggressive advanced cancers. But it created an epidemic of overdiagnosis and overtreatment for men with low-volume Gleason 6 cancer that is not expected to ever metastasize.

For me, the cure was worse than the disease. It seems I had a bad PSA reading (only 3.9 ng/mL, up from 3.2 ng/mL) on that day in December 2010 that I got on the prostate cancer railroad. The screening test was followed with another "bad" prostate day when I was diagnosed with a Gleason 6 tumor in a 2 mm smidge of tumor.

These results have not been replicated in three other biopsies and one multi-parametric MRI (mpMRI) since 2010. I was classified as a cancer patient forever.

PSA ensnared millions of men like me who had non-aggressive cancers that would never require surgery or radiation. We were like lambs to the slaughter as we followed our doctors' advice. I refused surgery and have been on active surveillance ever since.

But had I been diagnosed with more advanced cancer I might well be thanking, rather than damning, the PSA. That's the balancing game.

I suppose the debates were inevitable because PSA testing is such a poor tool.

In 2018, the USPSTF and the AAFP set off another debate when they recommended that men ages 55 to 69 should engage in shared decision-making with their physician about PSA screening.

The new guidelines emphasized something doctors should have done and probably did all along -- discussions with patients about decisions about treating prostate cancer to make a "shared-decision."

"Shared-decision making is essential for providing patient-centered care and can aid in addressing disparities in treatment. This process is especially important for cancer screening, like PSA testing, as there are sometimes real harms associated with screening," said Ada Stewart, MD, president of the AAFP. "And it is important for physicians to initiate these conversations, because many of our patients do not know to ask these important questions."

Siegel said making the decision on whether to be screened for prostate cancer is complex for men and their doctors and ought to be based on personal risk factors. include age, family history, and African ancestry. CDC offers to help men think about prostate cancer screening decisions.

The discussion on the USPSTF and AAFP guidelines mentioning age triggered yet another issue: Why cut off screening at 70 and above, especially if men are healthy?

Davis took issue with the USPSTF's 2018 recommendation that PSA screening not be done in men over 70. "The 2018 revision from the Task Force was impactful, although it wrote off the lives of men over 70, that I find irresponsible. In today's world, over-70s are frequently healthy contributors to society and will remain so for maybe 15 more years. Recently, we lost a 74-year-old who was diagnosed with de novo metastatic less than 12 months ago. Speak to his wife about whether men over 70 should be tested."

Krist noted that any man over 69 who has concerns or questions should talk with his doctor and decide what's right for him. "That's always important and the first step. But the studies to date have shown that screening men over the age of 69 has no net benefit. And it's not just life expectancy. It also has to do with the nature of the disease. False positives and overdiagnosis starts to go up dramatically over the age of 70, exposing men to more harms."

Krist said complications, biopsies, and treatment increase as men age. "All those things change the balance of the benefits and the harms. And the data are pretty clear that for men over 70, the net benefit is not there. But once again, individual men who think otherwise or have concerns, should talk with their doctor and think about what's right for them."

He emphasized that the guideline doesn't apply to men like me with confirmed prostate cancer.

Penson said, "The recommendation about men over age 70 is based on a clinical trial that was done 20 or 30 years ago, which compared surgery to watchful waiting in men with known prostate cancer. And they basically found that if you are over age 65 in that trial, you didn't have a benefit to surgery. So the general teaching has been that you've got to live more than 10 years to get a benefit from active therapy in terms of mortality, but that's an old trial and patients who were diagnosed in 2020 are a whole lot different than patients diagnosed in the '80s and '90s."

"And then, the other point is for a lot of guys, mortality's not the only thing they're worried about," Penson continued. "They're worried about the spread of disease. They're just worried about having cancer. So I think you really need to personalize that decision. It's important to stress in the recommendation that there are some men over age 70 that will garner a benefit. And if you look at the USPSTF recommendation, they do say that, but they bury it in the text."

Debu Tripathy, MD, editor-in-chief of Cure Today, , "A difficult line to walk in some cancer types is that between widespread screening to detect early disease and lower the death rate versus the overtreatment and associated consequences that can arise from it. This is particularly true when it comes to prostate cancer."

He said that based on the USPSTF's recommendations, the number of men screened for prostate cancer has declined. "That surely saved some patients from overtreatment, but at the same time it seems to have driven up the rate of advanced prostate cancers. Another problem with skipping screening is that it can deny men with low-grade prostate cancers the option of undergoing active surveillance so they will know if their disease starts growing quickly and needs more aggressive therapy," he said.

In the years ahead, these debates no doubt will continue as new research is published as these groups routinely review their guidelines.

USPSTF tends to review its guidelines every 5 years, which would mean there will be a review in 2023, or sooner if major research is published.

Penson said he doesn't think there is anything in the hopper regarding prostate cancer that will prompt AUA to immediately re-examine its guidelines on the use of PSA.

But he suspects AUA may soon begin reviewing its guidelines because of important research on mpMRI, an area where controversies are brewing over new technologies and PI-RADS, the rating system for the scans.

Looking ahead, Penson said of AUA's next review: "It's going to be about prostate cancer screening next time around. So, it's going to include guidance regarding the use of prostate MRI. It's going to include guidance around biomarkers such as 4K and the PHI [Prostate Health Index] test. And that is just starting now. So it's a few years away."

He added that he is not on the panel.

Krist said the USPSTF will review its guidelines in the next few years. An AAFP spokeswoman said her organization will follow suit when the Task Force reviews its guidelines.

Amidst the debate, it is important to remember that the PSA screening guidelines are just that: guidelines. They are not intended to dictate a standard course of screening or treatment. Rather, the guidelines are intended to serve as a guide for conversations between physicians and patients to determine what is best for each individual patient based on their health risks, family history, and screening preference.

What's needed more than new guidelines are new diagnostic approaches -- perhaps genomics combined with artificial intelligence/machine learning are most likely -- to separate those at high risk from those who aren't. If and when the science arrives, new guidelines can be written, and, potentially the debate, at last, will be over, and we can stop ducking pendulums.