It was the hardest paper he ever wrote, said E. David Crawford, MD, and that’s saying something when you’re one of the world’s top prostate cancer experts with a publication record about 600 entries long.
Yet the paper has the simplest of takeaways: Below 1.5, see you in five years. Above 1.5, get it checked out.
It turns out that 1.5 – a quantity, in nanograms, of prostate-specific antigen (PSA) in a milliliter of blood – is simple in the same way that E=MC2 is simple. That is, its elegance masks the work behind and the implications that flow from it.
Crawford is the University of Colorado School of Medicine’s chief of Urologic Oncology. He practices at UCHealth University of Colorado Hospital. His windowless Cancer Center office has two major decorative themes: marathon medals (he ran his 20th consecutive Boston Marathon last April) and top-doctors awards. Still in his surgical greens, he dumps a can of soup into a bowl and heats it in a small microwave. He eats this quick lunch while explaining why he and colleagues have devoted years to coming up with a straightforward prostate cancer screening standard that works for family physicians and strikes a balance between overtreatment and neglect.
Prostate cancer is the most common cancer in men, with about 220,000 new cases and 27,000 deaths from it in the United States each year. That’s within shouting distance of the 33,000 annual U.S. firearm casualties, 35,000 traffic fatalities, and 40,000 breast cancer deaths. But prostate cancer is different in at least one vital way: most of the time it’s so slow-growing it will never be a health issue. Autopsies show at least one-third of men age 50 and older to have had prostate cancer, Crawford said.
And while prostate cancer accounts for 26 percent of male cancer cases diagnosed in a given year, it leads to just 9 percent of cancer-related mortality. The trick with prostate cancer is less about figuring out who has it than about who has the sort of aggressive cancer that kills.
Preliminary screening has had a hard time determining which was which. PSA tests trigger about 1.3 million prostate biopsies a year, but about 85 percent of them find no cancer. Among those that do, there are countless examples of surgeries on low-grade cancers that may not have been necessary, each with potential complications ranging from infection to incontinence to impotence.
In 2009, Crawford was a lead author of a study of nearly 77,000 men, half of whom got annual PSA and digital rectal examination (DRE) screenings, half of whom didn’t. Seven to 10 years later, the researchers found the prostate cancer death rate to be about the same for both groups – about one in 5,000.
Using this and other data, the U.S. Preventative Services Task Force (USPSTF) recommended against PSA testing, a guideline that primary care doctors take seriously. Others disagree. The American Urological Association recommends prostate cancer screening every two years for men ages 55-69. The National Comprehensive Cancer Network suggests screening, with repeat testing every two to four years for men ages 45 to 75 with PSA scores less than 1 ng/mL; every one to two years for those with scores from 1-3 ng/mL; and biopsies for those with scores 3 ng/mL and higher.
Getting to 1.5
Crawford is anything but anti-prostate cancer screening. His efforts as founder (in 1989) and chairman of the Prostate Conditions Education Council underscore a longstanding belief in the value of screening.
“We believe that some people can benefit,” Crawford said. “You don’t need to throw the baby out with the bathwater.”
A study he published in 2011 brought him to 1.5. He and colleagues looked at data on 21,502 men from Henry Ford Health System in Michigan, considering those at least 40 years old with PSA values between 0 and 4.0 ng/mL and at least four years of follow-up. The researchers found prostate cancer rates to be 15 times higher – 7.85 percent versus 0.51 percent – among men with a PSA of 1.5 ng/mL or higher. Other studies have shown that 70 percent of men have PSAs below 1.5 ng/mL, and that half of all prostate cancer deaths were among men with a PSA of 1.6 ng/mL or greater before age 50.
“I wanted to know: is there a PSA cutoff that shows a danger zone? We found out that 1.5 is a cutoff for goodness or badness,” Crawford said.
Now it was a question of building a care plan and consensus around that cutoff, which was what made this latest paper so much work. Crawford talked with prostate cancer experts around the country, ultimately enlisting faculty from Johns Hopkins, New York University, M.D. Anderson, Memorial Sloan Kettering, the Cleveland Clinic, the National Cancer Institute and elsewhere to sign on as co-authors. Crawford added CU Urology resident Michael Maccini, MD; Urology research assistant Paul Arangua; and research fellow John Hoenemeyer, MD, to the effort.
User-friendly prostate cancer screening standard
The authors settled on an approach that includes a PSA screen as part of a standard annual checkup blood panel for men with more than 10 years of life expectancy. For men with a PSA below 1.5 ng/mL, that’s it for the next five years. Those with a PSA above 1.5 ng/mL should have further testing done. Doing so could save hundreds of thousands of biopsies each year in the United States.
Even the follow-on testing may not involve a biopsy. Crawford and Hoenemeyer recently wrapped up a study focusing on SelectMDx, a urine test that looks for two messenger RNA molecules associated with high-grade prostate cancers. They weren’t looking for how well it spots aggressive prostate cancer – that’s already been proven. Rather, of the 187 men who participated, none with a PSA lower than 1.5 ng/mL came back with SelectMDx results indicating serious cancers.
“That’s huge for us,” Hoenemeyer said. “It validates our clinical decision of not having Family Medicine refer a patient that has a PSA of less than 1.5.”
Though they published the study in the journal Urology, urologists are not Crawford’s target audience. The new approach will make the biggest difference among primary care doctors who perform 90 percent of U.S. prostate screenings, he said. He and his urologist colleagues are well aware of how hard it can be for primary care docs to squeeze a meaningful “informed decision” conversation about prostate cancer that may or may not be an issue into a 50-minute checkup – particularly when they may have to discuss pressing health issues like diabetes, obesity, smoking and more.
Add to that the confusion of conflicting expert-body prostate cancer testing recommendations and it’s no wonder that many primary care doctors were quite happily skipping prostate exams altogether for patients. But there’s a cost: some men who could have been saved with early detection have died.
Crawford’s approach would limit primary care prostate cancer discussions to the roughly one-third of men whose PSA tests came back above 1.5 ng/mL – ranging from 10 percent of men in the 41-45 age bracket to about half of 66-75 year olds. And while there will be rare cases of men with high-grade cancers despite low PSA scores, the 1.5 approach looks to be a balance worth striking, Crawford said.
“What I’ve found is there’s no perfect solution,” Crawford said. “But this is a way forward.”