By Shania Kennedy

– Stanford Medicine researchers have developed a precision medicine approach that can help flag and sort out normal prostate-specific antigen (PSA) changes caused by genetic factors unrelated to cancer, which could improve the accuracy of prostate-specific antigen (PSA) screening. prostate cancer.

The personalized approach, outlined in a study published last week in Medicine of Natureit is an attempt to address the overdiagnosis and overtreatment of prostate cancer that can result from PSA screening.

PSA screening is a common test for prostate cancer, but the test often suggests the presence of cancer when there isn’t any, the researchers explained. This has led the United States Preventive Services Task Force (USPSTF) to advise against PSA-based screening in patients over the age of 70 and to suggest that younger patients be given a choice whether or not to undergo screening.

Elevated PSA levels can be a sign of prostate cancer, but other factors, such as an enlarged prostate, infection, inflammation, or advanced age, can also cause changes in PSA.

“Some men have higher PSA levels because of their genetics,” John Witte, PhD, professor of epidemiology and population health and biomedical data sciences at Stanford and senior author of the study, said in the news release. “They don’t have cancer, but the higher PSA level leads to a cascade of unnecessary medical interventions like biopsy.”

Evaluations of the clinical utility of PSA screening have shown that of patients with elevated PSA, less than a third had prostate cancer. Research looking at the prevalence of prostate cancer among those with normal PSA also found that 15% of patients were later confirmed to have cancer after screening.

These findings suggest that there is a “noise” present in PSA screening that makes it less accurate in identifying prostate cancer, the research team indicated.

“To enhance the signal, which is the change in PSA levels caused by prostate cancer, we subtract the noise, which in this case comes from genetics,” said Linda Kachuri, PhD, assistant professor of epidemiology and population health at Stanford and the study’s lead author.

To reduce this genetic noise, the researchers evaluated the genomes and PSA levels of 95,768 men of European ancestry without prostate cancer. This analysis revealed that 30 to 40 percent of the change in PSA level was driven by genetic factors unrelated to cancer.

By separating these normal sources of noise within PSA screening, the research team aims to make PSA a more specific and accurate biomarker capable of determining the presence of prostate cancer.

The researchers successfully identified 128 sites within the genome that can affect patients’ PSA levels and developed a polygenic score to help calculate PSA levels by accounting for variations at these sites.

To evaluate the score, the research team applied it to a data set of just under 32,000 men without prostate cancer. Using this data, the score accurately predicted nearly ten percent of the change in PSA.

However, the tool was found to be significantly more effective among patients of European ancestry than their East Asian or African counterparts.

When the score was applied to a group of men with and without prostate cancer, as confirmed by biopsy, the researchers determined that about 30 percent of the cohort could have been spared from the biopsy.

Despite these successes, the tool has limitations. Notably, the score would have missed about nine percent of positive biopsies. The researchers indicated that most of these were cases of slow-growing tumors that may not have required treatment, but the oversight shows room for improvement in the score.

Because the tool was also developed with data primarily from men of European ancestry, the press release says the research team will collaborate on a larger study with the Million Veteran Program to incorporate more diverse patient data.

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