What is the interpretation of Prostate-Specific Antigen (PSA) levels?

From the Guidelines

Prostate-specific antigen (PSA) interpretation should consider both absolute values and changes over time, with a focus on PSA velocity and age-specific reference ranges, as recommended by the most recent guidelines 1. When interpreting PSA results, it's essential to understand that a level below 4.0 ng/mL is generally considered normal, but this can vary with age and other factors.

• A PSA level between 4.0-10.0 ng/mL suggests possible prostate cancer and requires further evaluation,
• while levels above 10.0 ng/mL indicate a higher likelihood of cancer. However, interpretation should never rely solely on absolute numbers, and PSA velocity (rate of change over time) is often more informative than a single measurement 1. Several factors can elevate PSA without cancer presence, including:
• prostate infection (prostatitis)
• benign prostatic hyperplasia (BPH)
• recent ejaculation
• prostate trauma
• or procedures like cystoscopy or catheterization. Certain medications like finasteride or dutasteride can artificially lower PSA by approximately 50% 1. For accurate interpretation, PSA should be evaluated alongside digital rectal examination findings, patient age, family history, and previous PSA values. When results are concerning, additional testing such as free PSA percentage, PSA density, prostate MRI, or biopsy may be warranted to determine if cancer is present 1. It's also important to consider the patient's individual risk factors, such as family history and age, when making decisions about PSA testing and interpretation 1. Ultimately, a comprehensive approach to PSA interpretation, taking into account both the benefits and limitations of testing, is crucial for informed decision-making and optimal patient care.

From the FDA Drug Label

In clinical trials, dutasteride reduced serum PSA concentration by approximately 50% within 3 to 6 months of treatment. This decrease was predictable over the entire range of PSA values in subjects with symptomatic BPH, although it may vary in individuals Dutasteride may also cause decreases in serum PSA in the presence of prostate cancer. To interpret serial PSAs in men taking dutasteride, a new PSA baseline should be established at least 3 months after starting treatment and PSA monitored periodically thereafter Any confirmed increase from the lowest PSA value while on dutasteride may signal the presence of prostate cancer and should be evaluated, even if PSA levels are still within the normal range for men not taking a 5 alpha-reductase inhibitor. Noncompliance with dutasteride may also affect PSA test results To interpret an isolated PSA value in a man treated with dutasteride for 3 months or more, the PSA value should be doubled for comparison with normal values in untreated men.

Interpretation of PSA in men taking dutasteride:

• New baseline: Establish a new PSA baseline at least 3 months after starting treatment.
• Monitoring: Monitor PSA periodically after establishing the new baseline.
• Increase in PSA: Any confirmed increase from the lowest PSA value while on dutasteride may indicate prostate cancer.
• Isolated PSA value: Double the PSA value for comparison with normal values in untreated men if the patient has been taking dutasteride for 3 months or more. 2

From the Research

Interpretation of PSA

• The interpretation of Prostate-Specific Antigen (PSA) levels is crucial in the early detection of prostate cancer. A study published in 2017 3 compared the efficacy of digital rectal examination and serum PSA in the early detection of prostate cancer, finding that PSA detected significantly more tumors than digital rectal examination.
• The study found that a PSA level of greater than 4 μg./l. was a significant indicator of prostate cancer, with a cancer detection rate of 4.6% for PSA and 5.8% for the combination of PSA and digital rectal examination.
• Another study published in 2020 4 analyzed the value of digital rectal examination as a predictor of upgrading in a population of men with prostate cancer treated with active surveillance, finding that a suspicious digital rectal examination was a predictor of clinically significant prostate cancer.
• A study published in 1999 5 evaluated the detection rate of prostate cancer in men with suspicious digital rectal examination findings and serum PSA levels of 4 ng./ml. or less, finding that the positive predictive value of a suspicious digital rectal examination was appreciable in men with low serum PSA.
• The risk profiles and treatment patterns among men diagnosed with prostate cancer and a PSA level below 4.0 ng/ml. were studied in 2010 6, finding that men with a PSA level of 4.0 ng/mL or lower represent 14% of incident prostate cancer cases, and that most men diagnosed with prostate cancer with a PSA threshold below 4.0 ng/mL had low-risk disease but underwent aggressive local therapy.
• A randomized trial published in 2021 7 evaluated digital rectal examination in prostate cancer screening at PSA level 3.0-3.9 ng/ml, finding that the results do not support the utility of digital rectal examination as a screening test for prostate cancer at this PSA level, while the results regarding free/total PSA determination were more encouraging.

PSA Levels and Prostate Cancer Detection

• A PSA level of greater than 4 μg./l. is a significant indicator of prostate cancer, with a cancer detection rate of 4.6% for PSA and 5.8% for the combination of PSA and digital rectal examination 3.
• The positive predictive value of a suspicious digital rectal examination is appreciable in men with low serum PSA, with values of 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 5.
• Men with a PSA level of 4.0 ng/mL or lower represent 14% of incident prostate cancer cases, and most men diagnosed with prostate cancer with a PSA threshold below 4.0 ng/mL had low-risk disease but underwent aggressive local therapy 6.

Digital Rectal Examination and Prostate Cancer Screening

• Digital rectal examination is part of the clinical evaluation of men on active surveillance for prostate cancer, and a suspicious digital rectal examination is a predictor of clinically significant prostate cancer 4.
• The utility of digital rectal examination as a screening test for prostate cancer at serum PSA level 3.0-3.9 ng/ml. is not supported by the results of a randomized trial, while the results regarding free/total PSA determination were more encouraging 7.