Prostate Biomarkers: Prostate-Specific Antigen (PSA)

Optimal Takeaways

Prostate-specific antigen increases with prostate cancer and other prostate disorders, including benign prostatic hypertrophy. Increasing PSA in the blood likely indicates inflammation, tissue damage, and increased cancer risk. A low PSA suggests a low risk of prostate cancer.

Standard Range: 0.00 – 4.00 ng/mL (0.00 – 4.00 ug/L)

The ODX Range: 0.00 – 2.00 ng/mL (0.00 – 2.00 ug/L)    

Low levels of PSA are associated with decreased risk of prostate cancer, although levels can be reduced by up to 50% with medication, including diethylstilbestrol and finasteride (Pagana 2021).

High levels of PSA can occur with prostate cancer, benign prostatic hypertrophy, urinary infection, prostatitis, rectal exam, biopsy, TURP procedure, and recent ejaculation within 24 hours of blood test (Pagana 2021).

Overview

Prostate-specific antigen (PSA) is a protein that increases with prostate disorders, including infection, benign hypertrophy, and prostate cancer, which can significantly increase levels. The degree of increase is believed to reflect the degree of tumor burden (Pagana 2021).

Total PSA levels will be highest in prostate cancer, especially above 6.8 ng/mL, and lowest in benign prostatic hypertrophy (BPH). A PSA above 10 ng/mL usually triggers a biopsy, while levels below 2.00 ng/mL are least likely to be associated with prostate cancer. Females can also produce PSA, and levels may increase due to cystitis or various carcinomas, including urethra, bladder, kidney, adrenal, hepatic, lung, and breast (Prcic 2016).

A review of data from 500,000 men found that 70% of those 45-70 years old maintained a PSA below 1.5 ng/mL. Researchers recommend using the 1.5 ng/mL cut-off to determine which individuals need further workup and more aggressive screening (Crawford 2016).

However, researchers conducting a meta-analysis comprising 721,718 men warn that aggressive screening may only slightly reduce prostate-specific mortality. They also emphasize the risk of more false positives and biopsies, which carry the risk of complications, including sepsis, urinary incontinence, and erectile dysfunction. Data suggest that approximately 2.3% of men with a PSA below 4 ng/mL and a Gleason score of 7 or above will have clinically meaningful disease (Ilic 2018).

Total PSA reflects complexed and free PSA and is a sensitive marker of prostate cancer incidence and recurrence. However, further evaluation of free to total PSA ratio (%free PSA) may be of additional diagnostic and prognostic value. The %free PSA will be lower in those with prostate cancer versus BPH and may help predict morbidity, especially with a PSA in the 4-10 ng/mL range (Moradi 2019). A %free PSA below 25% in those with a total PSA of 2.6-4 ng/mL is associated with increased cancer risk and should be evaluated further (Roehl 2002).

PSA levels should remain undetectable following radical prostatectomy, and even a slight increase should be investigated in such cases. A low PSA does not necessarily rule out prostate cancer, including high-grade prostate cancer. Although uncommon, prostate cancer has been diagnosed in men with a PSA of 0.5 ng/mL or below (Mohler 2010).

References

Crawford, E David et al. “An Approach Using PSA Levels of 1.5 ng/mL as the Cutoff for Prostate Cancer Screening in Primary Care.” Urology vol. 96 (2016): 116-120. doi:10.1016/j.urology.2016.07.001

Ilic, Dragan et al. “Prostate cancer screening with prostate-specific antigen (PSA) test: a systematic review and meta-analysis.” BMJ (Clinical research ed.) vol. 362 k3519. 5 Sep. 2018, doi:10.1136/bmj.k3519

Mohler, James et al. “NCCN clinical practice guidelines in oncology: prostate cancer.” Journal of the National Comprehensive Cancer Network : JNCCN vol. 8,2 (2010): 162-200. doi:10.6004/jnccn.2010.0012

Moradi, Afshin et al. “Beyond the biomarker role: prostate-specific antigen (PSA) in the prostate cancer microenvironment.” Cancer metastasis reviews vol. 38,3 (2019): 333-346. doi:10.1007/s10555-019-09815-3

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Prcic, Alden et al. “Usefulness of Total PSA Value in Prostate Diseases Diagnosis.” Acta informatica medica : AIM : journal of the Society for Medical Informatics of Bosnia & Herzegovina : casopis Drustva za medicinsku informatiku BiH vol. 24,3 (2016): 156-61. doi:10.5455/aim.2016.24.156-161

Roehl, Kimberly A et al. “Robustness of free prostate specific antigen measurements to reduce unnecessary biopsies in the 2.6 to 4.0 ng./ml. range.” The Journal of urology vol. 168,3 (2002): 922-5. doi:10.1097/01.ju.0000024660.18328.2d