What yearly increase in Prostate-Specific Antigen (PSA) is concerning?

From the Guidelines

A yearly increase in PSA of 0.35 ng/mL or greater for men with a baseline PSA below 4 ng/mL, and 0.75 ng/mL or greater for men with a baseline PSA between 4-10 ng/mL, is generally considered concerning and warrants further evaluation. This rate of increase, known as PSA velocity, is an important indicator that may suggest the presence of prostate cancer rather than benign conditions. When evaluating PSA changes, it's essential to have multiple measurements over time, ideally using the same laboratory to ensure consistency 1. If a concerning PSA velocity is detected, further evaluation typically includes a digital rectal examination, possibly imaging studies such as MRI, and potentially a prostate biopsy depending on other risk factors. The significance of PSA velocity is based on the observation that prostate cancer often causes more rapid increases in PSA levels than benign conditions like prostate enlargement (BPH) 1. However, PSA can also be temporarily elevated by factors such as recent ejaculation, prostate infection, or trauma, so these should be considered when interpreting results.

Some key points to consider when evaluating PSA velocity include:

• For men with PSA < 4 ng/mL, a PSA velocity of 0.35 ng/mL per year is suspicious for the presence of cancer 1
• For men with PSA 4-10 ng/mL, a PSA velocity of 0.75 ng/mL per year is suspicious for cancer 1
• PSA velocity in men with PSA > 10 ng/mL has not been determined useful 1
• Measurement should be made on at least 3 consecutive specimens drawn over at least an 18- to 24-month interval 1
• Biologic variability and/or prostatitis may be confounding factors in determining PSA velocity; therefore, antibiotic therapy and repeated PSA measurements may be considered to minimize these sources of confusion 1.

It's also important to note that while PSA velocity can be a useful tool in evaluating the risk of prostate cancer, it is not without its limitations. Some studies have suggested that PSA velocity may not provide independent predictive information related to the risk of prostate cancer beyond that provided by PSA alone 1. However, other studies have found that PSA velocity can be a useful indicator of prostate cancer risk, particularly in men with a baseline PSA below 4 ng/mL 1.

In clinical practice, the decision to perform a biopsy or refer to a urologist should be based on a comprehensive evaluation of the patient's individual risk factors, including PSA velocity, PSA level, digital rectal examination results, and other relevant factors 1.

From the Research

Yearly Increase in PSA Concerning Prostate Cancer

• A yearly increase in PSA of more than 0.75 ng/mL per year is considered concerning for prostate cancer, as indicated by a study published in the Journal of the American Medical Association (JAMA) 2.
• Any increase in PSA from nadir should be considered suspicious for malignancy, according to a study published in the journal Urologia 3.
• The rate of PSA increase is a significant predictor of prostate cancer, and a high PSA velocity is associated with an increased risk of prostate cancer, as suggested by a study published in JAMA 2.
• However, it is essential to consider other factors such as digital rectal examination, age, family history of prostate cancer, and imaging techniques in the clinical and diagnostic follow-up, as stated in a study published in Urologia 3.

Factors Affecting PSA Levels

• 5-alpha reductase inhibitors (5ARIs) can decrease serum PSA levels by approximately 50%, which may affect the interpretation of PSA test results, as reported in a study published in Urologia 4.
• The use of 5ARIs does not appear to adversely affect prostate cancer detection after transrectal ultrasound (TRUS)/magnetic resonance imaging (MRI) fusion biopsy, as suggested by a study published in Scientific Reports 5.
• The accuracy of PSA testing is not compromised by 5ARI treatment, and may even be increased, according to a study published in Urologia 4.

Diagnostic Considerations

• An isolated elevation in PSA level should be confirmed several weeks later before proceeding with further testing, including prostate biopsy, as recommended by a study published in JAMA 2.
• The Prostate Imaging-Reporting and Data System (PI-RADS) distribution and clinically significant prostate cancer detection rates are not significantly affected by 5ARI exposure, as reported in a study published in Biomolecules 6.