The prostate-specific antigen (PSA) test is a blood analysis that measures levels of a protein produced by prostate cells. This protein plays a role in fertility by helping to liquefy semen, allowing sperm to move more freely. Both healthy and cancerous prostate cells generate PSA, but cancer cells tend to release more of it into the bloodstream due to their leakier nature. Since the early 1990s, PSA screening has become a common method for detecting prostate cancer, though it remains a topic of debate in medical circles.
Prostate cancer often progresses slowly, and one concern with PSA testing is that it may identify many low-grade tumors that might never pose a threat during a man’s lifetime. However, research indicates that the test can save lives by catching cancers at earlier, more treatable stages. The U.S. Preventive Services Task Force (USPSTF), a volunteer panel of experts in prevention and evidence-based medicine, recommends that doctors discuss the advantages and disadvantages of PSA screening with men aged 55 to 69. For those over 70, the USPSTF advises against screening, and it offers no guidance for men under 55.
Certain groups face higher risks and may benefit from earlier screening. For example, Black men are approximately twice as likely to be diagnosed with and die from prostate cancer compared to white men. The American Cancer Society (ACS) suggests that Black men consider PSA screening starting at age 45. Earlier screening is also recommended for men with close relatives who developed prostate cancer at a young age or for those with genetic mutations like BRCA1 and BRCA2 that increase cancer risk.
It’s important to note that factors unrelated to cancer can temporarily elevate PSA levels. Activities that put pressure on the prostate, such as cycling or sexual activity, should be avoided for two to three days before testing. Health issues like infections, inflammation (prostatitis), or benign prostatic hyperplasia—a common enlargement in older men—can also cause PSA spikes.
Generally, a PSA level above 4 nanograms per milliliter (ng/mL) is considered abnormal, but this threshold can vary with age. Dr. Marc B. Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of the Harvard Medical School Guide to Prostate Diseases, explains that a PSA of 3.5 ng/mL in a man in his 40s is “definitely abnormal,” while a level of 5.5 ng/mL in someone in their 60s might not be. PSA values exist on a continuum, with higher levels correlating with a greater likelihood of prostate cancer.
However, the test is not foolproof. Studies show that up to 15% of men with PSA levels below 4 ng/mL actually have prostate cancer, and some of these tumors are clinically significant. Conversely, high-grade cancers might not cause a substantial rise in PSA because these aggressive cells can lose their ability to produce the protein.
When an abnormal PSA result occurs, the follow-up approach has evolved. In the past, elevated readings often led directly to a prostate biopsy. Today, a magnetic resonance imaging (MRI) scan is frequently used first to identify suspicious areas in the prostate. In Europe and some U.S. hospitals, a negative MRI might allow a man to skip an initial biopsy altogether, though many physicians still prefer to start with a biopsy and then use periodic PSA tests and MRI scans to decide if further biopsies are necessary.
If an initial biopsy and MRI indicate cancer, doctors may perform a targeted biopsy focused on the areas highlighted by the MRI. Once cancer is confirmed, treatment decisions follow. Many low-grade cancers are now managed with active surveillance, involving regular monitoring through biopsies and MRI scans, with treatment initiated only if the disease worsens. Higher-grade cancers typically require immediate intervention.
Dr. Garnick emphasizes that “the goal of this risk-adapted approach to screening” is to “identify clinically significant cancers that actually do need treatment while decreasing diagnoses of clinically insignificant cancers that do not.”
To refine the PSA test and reduce unnecessary biopsies, several variations have been developed. Free PSA testing measures the portion of PSA not bound to other proteins, with lower percentages linked to higher cancer risk. PSA density calculates the ratio of total PSA to prostate volume, with values of 0.15 ng/mL or higher potentially indicating cancer. PSA velocity tracks changes in PSA levels over time, and the Prostate Health Index combines total PSA, free PSA, and proPSA, with some evidence suggesting it offers more accurate cancer diagnosis than PSA alone.
This overview focuses on PSA screening for prostate cancer. In a subsequent discussion, we will explore how the PSA test is used to monitor and manage patients already diagnosed with the disease.
