What is the normal level of Prostate-Specific Antigen (PSA)?

From the Guidelines

The normal level of PSA is generally considered to be below 4.0 nanograms per milliliter (ng/mL) of blood, though this can vary based on age and other factors, with recent guidelines suggesting consideration of biopsies for men with PSA levels in the range of 2.6 to 4.0 ng/mL 1.

Key Considerations

• PSA levels naturally increase with age as the prostate enlarges, and levels below 2.5 ng/mL are typically considered normal for men in their 40s, while men in their 50s might have slightly higher baseline levels.
• Elevated PSA levels don't necessarily indicate cancer but could reflect other conditions like prostatitis, benign prostatic hyperplasia (BPH), or recent ejaculation.
• Regular PSA testing is recommended for men starting at age 50, or earlier for those with risk factors like family history of prostate cancer or African American ethnicity.

Diagnostic Approach

• Any significant rise in PSA levels over time (PSA velocity) is often more concerning than a single elevated reading, which is why tracking changes over time provides valuable diagnostic information.
• The Prostate Cancer Prevention Trial (PCPT) showed that 15% of men with a PSA level of 4.0 ng/mL or less and a normal DRE had prostate cancer diagnosed on end-of-study biopsies, highlighting the importance of considering PSA levels in the context of overall risk assessment 1.

Guideline Recommendations

• The NCCN guidelines recommend considering biopsies for men with PSA levels in the range of 2.6 to 4.0 ng/mL, based on findings that high-grade prostate cancers detected through biopsy are not rare among men with PSA levels of 4.0 ng/mL or less 1.
• The American Cancer Society guidelines suggest that men with a first-degree relative diagnosed before age 65 years should begin testing at age 45 years, and those at even higher risk could begin testing at age 40 years 1.

From the Research

Normal Level of PSA

The normal level of Prostate-Specific Antigen (PSA) is a topic of discussion in various studies.

• A study published in 1995 2 derived age-specific upper limits for PSA level in men 50-74 years of age with no clinical evidence of prostatic carcinoma.
• The study found that newly-derived upper limits calculated by each method in the 50-54 and the 70-74 age group were 3.9 ng/mL and 7.6 ng/mL (mean +2 SD), 5.2 ng/mL and 14.0 ng/mL (99th percentile), and 4.7 ng/mL and 8.2 ng/mL (97.5% prediction interval).
• However, the study concluded that no upper limits derived from these three methods yielded adequate sensitivity to detect cancer and recommended that an upper limit of 4.0 ng/mL be used in all men 50-74 years of age.
• Another study published in 1998 3 found that most prostate cancers missed by raising the upper limit of normal PSA for men in their sixties are clinically significant, with a positive biopsy rate of 31.5% and more than 80% of the cancers detected satisfying criteria that almost always predict clinically significant cancer.
• A study published in 1999 4 evaluated the detection rate of prostate cancer in men with suspicious digital rectal examination findings and serum PSA 4 ng./ml. or less, and found that the positive predictive value of a suspicious digital rectal examination was 5,14, and 30% in men with PSA 0 to 1.0,1.1 to 2.5, and 2.6 to 4.0 ng./ml., respectively.
• A study published in 2012 5 examined the effect of 5α-reductase inhibitor therapy on prostate cancer detection in men with persistently increased or fluctuating PSA and prior negative prostate cancer biopsy, and found that the magnitude of change in serum PSA after 5α-reductase inhibitor therapy may be useful in diagnosing prostate cancer in patients with persistently increased or fluctuating PSA and prior negative prostate biopsy.
• A study published in 2020 6 analyzed the value of digital rectal examination as a predictor of upgrading in a population of men with prostate cancer treated with active surveillance, and found that a suspicious digital rectal examination at confirmatory biopsy, particularly if the digital rectal examination at diagnosis was negative, was a predictor of clinically significant prostate cancer.

Key Findings

• The normal level of PSA is generally considered to be 4.0 ng/mL or less 2.
• However, the optimal upper limit of normal PSA may vary depending on age and other factors 3, 2.
• Digital rectal examination can be a useful tool in detecting prostate cancer, particularly in men with suspicious findings and PSA levels 4 ng./ml. or less 4, 6.
• The magnitude of change in serum PSA after 5α-reductase inhibitor therapy may be useful in diagnosing prostate cancer in patients with persistently increased or fluctuating PSA and prior negative prostate biopsy 5.