MONDAY, June 5, 2023 (HealthDay News) — Essentially the most common screening test for prostate cancer so often returns a false positive result that it’s now not really useful for men older than 70, and it’s offered as a private alternative for younger men.
But researchers think they’ve found a method to make the blood test for prostate-specific antigen (PSA) accurate enough to significantly reduce overdiagnosis and higher predict dangerous cancers.
By calibrating PSA levels to every man’s genetics, doctors could control for other aspects which may cause levels to be elevated, based on researchers at Stanford Medicine, in California.
The researchers envisioned combining the regular blood-based PSA test with an extra genetic evaluation that detects inherited genetic variants that may affect PSA levels.
Elevated PSA levels generally is a sign of prostate cancer, but levels can be high because of other issues like inflammation, infection, an enlarged prostate or simply old age, the study authors said in background notes.
“Some men have higher PSA levels because of their genetics,” senior researcher John Witte, a Stanford professor of epidemiology and population health, said in a university news release. “They don’t have cancer, but the upper PSA level results in a cascade of unnecessary medical interventions like biopsy.”
By one estimate, lower than one-third of men with elevated PSA levels were confirmed by a biopsy to have prostate cancer, the researchers reported. Furthermore, 15% of men with normal PSA levels were later found to have prostate cancer.
But health experts are reluctant to write down off the PSA test completely, provided that prostate cancer rates are on the rise in the US.
Prostate cancer rates rose by 3% a 12 months between 2014 and 2019 after 20 years of decline, and advanced prostate cancers increased by about 5% a 12 months, the newest American Cancer Society statistics show.
The issue is that the signal delivered by current PSA screening — a person’s risk of prostate cancer — is simply too often mixed with background noise, the researchers explained.
“To enhance the signal, which is the variation in PSA levels brought on by a prostate tumor, we subtract out the noise, which on this case comes from genetics,” said lead researcher Linda Kachuri, an assistant professor of epidemiology and population health at Stanford.
For this study, the investigators checked out the genomes and PSA levels of nearly 96,000 men without prostate cancer to raised understand the genetics behind normal variation in PSA levels. The info had been collected as a part of earlier studies and included mostly men of European ancestry.
Through this evaluation, the researchers estimated that 30% to 40% of the variation present in each man’s PSA levels constitutes “noise,” determined by genetic aspects unrelated to cancer.
“Specifically, what we’re attempting to capture are the genetic determinants of normal PSA variation,” Kachuri explained.
“That is different from our usual research deciphering the genetic basis of cancer,” Witte said. “We wish to remove the non-cancer-related part that’s making PSA a less specific biomarker.”
The researchers identified 128 specific sites within the genome that may affect a person’s PSA level, after which developed a method to account for these normal genetic variations when calculating what they called a PSA polygenic rating.
“A polygenic rating is a quantitative way of summarizing someone’s genetic predisposition for a trait in a single value,” Kachuri said.
The researchers then tested their PSA polygenic rating against data from a separate group of nearly 32,000 men without prostate cancer.
They found that the rating could predict near 10% of variation in PSA levels. Nonetheless, it was rather more effective amongst men of European ancestry than amongst men of East Asian or African ancestry.
Next, the researchers applied their rating to a mixed group of men with and without prostate cancer, as confirmed by biopsy. The outcomes showed that their PSA test could have spared roughly 30% of those men a biopsy.
The adjusted PSA levels particularly improved detection of the more aggressive types of prostate cancer, although the profit was noticeable only in men of European ancestry, based on the report.
“What we’re really frightened about are those aggressive cases, so the proven fact that we’re capable of show that genetically adjusted PSA is more predictive of aggressive disease is admittedly promising,” Kachuri said.
Unfortunately, the adjusted PSA levels also would have missed roughly 9% of positive biopsies, the findings showed.
Nearly all of these missed cases were slow-growing tumors, which usually are not as dangerous and should not even require treatment. Nonetheless, the misclassifications point to room for improving the rating, the study authors said.
The team next plans a bigger study that can include more men from diverse populations, to raised improve the accuracy of the test.
“Ideally, we would like to give you a single rating that works well for everyone, across the spectrum of ancestry,” Kachuri said.
Even a small improvement in screening could save lives, provided that one in nine men in the US will likely be diagnosed with prostate cancer and one in 40 will die from it, the researchers said.
The brand new study was published June 1 in Nature Medicine.
More information
The U.S. National Cancer Institute has more concerning the PSA test.
SOURCE: Stanford University, news release, June 1, 2023