Should We Use PSA to Find Active Surveillance Candidates?

As a patient on active surveillance (AS) since 2010, I always considered AS a solution for men like me with very low-risk prostate cancer. Is it time to rethink that?

E. David Crawford, MD, a urologist and a long-time prostate cancer researcher, surprised me when he explained that in his view, prostate-specific antigen (PSA) testing should not focus on finding men to go on AS.

Rather, he argues that PSA testing should be used to determine which men do not need PSA testing on an annual or more frequent basis, as this can help avoid unnecessary biopsies.

In an interview with MedPage Today, Crawford said that PSA used along with molecular testing can help many men stay off routine PSA for perhaps 5 to 10 years before repeating it, modeling it after colonoscopies. He said his approach will save many men from biopsies, which carry risks of sepsis and other infections, and also spare them years of worry from “anxious surveillance.”

Back in the 1980s, Crawford started working with the then new test to effectively follow men with more advanced prostate cancer.

One of his patients with metastatic prostate cancer asked the urologist a simple question: Why not use PSA testing to find prostate cancers early?

The patient had some clout. He was Perry Lieber, operations manager for one of the world’s richest men at the time, Howard Hughes.

Crawford said he was resistant to the screening idea at first because he didn’t think men would go for it.

In 1986, the FDA approved the PSA test to monitor the progression of prostate cancer in men who had already been diagnosed with the disease.

The 2014 book, The Great Prostate Hoax: How Big Medicine Hijacked the PSA Test and Caused a Public Health Disaster, spells out how the FDA, under pressure from the manufacturer and patient advocates, in 1994 approved the use of the PSA test with a digital rectal exam to test asymptomatic men for prostate cancer.

The controversy continues. Some lives were saved, but widespread testing was accompanied by an epidemic of overdiagnosis and overtreatment of low-risk prostate cancer.

Active surveillance was developed 30 years ago as a strategy for close monitoring of men with low-risk disease. Crawford said the arrival of molecular tests of prostate cancer tissue changed the game once again.

PSA blood levels of 4.0 ng/mL sent men from the primary care physician to the urologist, with the consequence being in most cases, until recently, “definitive” treatment.

Crawford suggests a new cutoff of 1.5 ng/mL.

“I picked that cutoff because when you start going above that you do have a risk of prostate cancer that is significant. And if you let it get above a cutoff of 4, you’ll find more cancers but you’ll also miss some bad ones that might have been found earlier,” he said.

His research showed that with this approach, 70% of men could bypass biopsies and avoid years of anxiety. He suggests follow-up in 5 to 10 years.

“This is where you get into trouble and that’s where we started integrating what already had been done in a lot of other cancers — molecular markers — to find the people who had a problem. Everybody got very proud of themselves for finding all these cancers and putting patients on active surveillance rather than doing surgery or radiation,” said Crawford, who runs the website PCmarkers.com.

“My point is we don’t want to find patients for active surveillance. It is an area that creates a lot of mental anguish. It creates a lot of follow-up biopsies. It generates a lot of MRIs. Markers can help us,” he said, referring to such tests as SelectMDx, 4Kscore, and phi.

He contends that family practitioners, who order about 90% of PSAs, need a simple figure to focus on: 1.5 ng/mL.

“They can’t remember all the nuances. They get turned off by it. When we find somebody is at risk, we do a molecular marker,’ said Crawford.

“It’s amazing that doctors don’t rely on markers to help them to make a decision on when to biopsy. And that’s what my whole direction is about — to eliminate active surveillance by not finding people that go on active surveillance. We want to find people that need active treatment, surgery, and radiation.”

The proposal elicits mixed responses.

Family physician Stephen Spann, MD, founding dean of the College of Medicine and vice-president for Medical Affairs at the University of Houston, is concerned that the lower the cutoff of PSA, the greater the risk of increased false-positive rates and the greater the detection of “minimal cancer.”

He said, “I would just want to know, what is the evidence that this is going to make a difference in patient survival or even quality of life. We don’t even know — we don’t even have hard data today — what early detection leads to if you get prostate cancer. The trials that were done on that 15 or 20 years ago were sort of a toss-up. It’s a personal decision because we don’t have really rock-hard, solid evidence that early detection leads to prolonged survival. And if you get early detected and treated, you have a pretty high chance of becoming impotent and incontinent.”

But Todd Morgan, MD — chief of urologic oncology at Michigan Medicine in Ann Arbor, and principal investigator of two large randomized controlled trials evaluating tissue-based biomarkers in men with localized prostate cancer — said he agrees with the idea that PSA can be used as a risk stratification tool. Morgan, who until last year served on the National Comprehensive Cancer Network guidelines panel for low-risk prostate cancer, noted that the NCCN guideline has a PSA cutoff of 1.0.

“If your PSA is really low, you probably don’t need further PSA screening for 5 years. There are pros and cons because the higher the threshold you’re going to start to miss a few cases of cancer, but you can rule out a whole lot more patients,” he said.

Howard Wolinsky is a Chicago-based medical writer. He has written the blog, “A Patient’s Journey,” for MedPage Today since 2016. He is the editor of the Substack newsletter, TheActiveSurveillor.com.

Active Surveillance Patients International and the AnCan Virtual Support Group for Active Surveillance are holding a webinar with other groups, “Your Voice in the Future of Active Surveillance” at 11 a.m. Eastern Time on April 22. The free meeting features top physicians in the field internationally, including Laurence Klotz, MD, of the University of Toronto, and Peter Carroll, MD, of the University of California, San Francisco. Register here.