Prostate-specific antigen (PSA) is a protein produced by prostate cells, both normal and cancerous. Elevated PSA may indicate prostate cancer, but also benign prostatic hyperplasia, prostatitis, or simple prostate size. The test is sensitive but not specific, it detects a lot of prostate abnormality without reliably distinguishing between clinically significant cancer and conditions that will never cause harm. This is the core of the screening controversy.

What PSA Levels Mean

PSA is measured in nanograms per milliliter (ng/mL). Traditional risk thresholds:

  • Below 4.0 ng/mL: Historically considered normal
  • 4.0-10.0 ng/mL: “Gray zone”, elevated risk, further evaluation warranted
  • Above 10.0 ng/mL: Significantly elevated, high probability of prostate abnormality

These thresholds are imperfect. Prostate cancer is found in approximately 15% of men with PSA below 4.0 ng/mL. Many men with PSA between 4.0 and 10.0 do not have cancer, the positive predictive value in this range is approximately 25-30%.

PSA velocity (rate of rise over time) and PSA density (PSA relative to prostate volume on ultrasound) provide additional context. A rapid rise in PSA over 1-2 years is more concerning than a stable elevated value.

Who Should Be Tested and When

The US Preventive Services Task Force (USPSTF) recommends that men aged 55-69 discuss PSA screening with their doctor before deciding whether to test. For men 70 and older, the USPSTF recommends against routine PSA screening. For men under 55, routine screening is generally not recommended except in high-risk groups.

High-risk groups with recommendations for earlier or more frequent screening:

  • African American men: 2-3 times higher incidence and higher mortality; many guidelines recommend beginning screening at 40-45
  • Men with first-degree relative with prostate cancer: Particularly if the relative was diagnosed before 65

The American Cancer Society recommends that men at average risk begin the screening conversation at 50, while high-risk men should begin at 40-45.

What Happens When PSA Is Elevated

An elevated PSA does not diagnose cancer, it triggers further evaluation. Traditional next steps:

Prostate biopsy: Historically the standard follow-up for elevated PSA. A needle biopsy samples 12 or more cores of prostate tissue under ultrasound guidance, which can cause bleeding, infection, and urinary symptoms. Biopsy detects cancer but also detects low-grade cancers that would never have caused harm.

MRI-guided biopsy: Multiparametric MRI (mpMRI) of the prostate before biopsy has substantially improved the biopsy process. mpMRI identifies suspicious lesions and guides targeted biopsy to those lesions, reducing unnecessary biopsies in men with low-suspicion PSA elevations and reducing the detection of clinically insignificant low-grade cancers.

PSA 4K Score or Prostate Health Index (PHI): Blood tests that combine PSA with other markers to produce a more specific risk estimate. These reduce unnecessary biopsies in men with elevated PSA by identifying those at lower risk.

The Overdiagnosis Problem

The central concern with PSA screening is overdiagnosis: detecting cancers that would never have caused symptoms or shortened life. Because PSA screening has driven a large increase in prostate cancer diagnoses, and because a substantial proportion of these cancers are Gleason grade 6 (the lowest grade), many men have undergone treatment, with its associated risks of incontinence and erectile dysfunction, for cancers that would never have harmed them.

Active surveillance (regular PSA testing, periodic biopsy, and MRI monitoring without immediate treatment) is now standard of care for low-risk prostate cancer. For a man with Gleason 6 prostate cancer, active surveillance defers treatment until there is evidence of progression, avoiding treatment harms in men whose cancer would not have shortened their life.

PSA on TRT

Testosterone replacement therapy raises PSA in most men, typically by 0.3-1.0 ng/mL. A baseline PSA should be checked before starting TRT, and PSA should be monitored at 3-6 months after starting therapy and then annually. A rise exceeding 0.75 ng/mL per year or a level above 4.0 ng/mL warrants urology evaluation before continuing TRT.

The relationship between testosterone and prostate cancer risk is discussed in TRT Side Effects: What the Research Actually Shows. For a broader overview of prostate health by decade, see Prostate Health Basics: What Men Need to Know at 40, 50, and 60.