Prostate-Specific Antigen (PSA) Test (Fact Sheet)

What does an increase in PSA level mean for a man who has been treated for prostate cancer?

If a man’s PSA level rises after prostate cancer treatment, his doctor will consider a number of factors before recommending further treatment. Additional treatment based on a single PSA test is not recommended. Instead, a rising trend in PSA level over time in combination with other findings, such as an abnormal result on imaging tests, may lead a man’s doctor to recommend further treatment.

How are researchers trying to improve the PSA test?

Scientists are investigating ways to improve the PSA test to give doctors the ability to better distinguish cancerous from benign conditions and slow-growing cancers from fast-growing, potentially lethal cancers. None has been proven to decrease the risk of death from prostate cancer. Some of the methods being studied include:

• Free versus total PSA. The amount of PSA in the blood that is “free” (not bound to other proteins) divided by the total amount of PSA (free plus bound) is denoted as the proportion of free PSA. Some evidence suggests that a lower proportion of free PSA may be associated with more aggressive cancer.
• PSA density of the transition zone. The blood level of PSA divided by the volume of the transition zone of the prostate. The transition zone is the interior part of the prostate that surrounds the urethra. Some evidence suggests that this measure may be more accurate at detecting prostate cancer than the standard PSA test.
• Age-specific PSA reference ranges. Because a man’s PSA level tends to increase with age, it has been suggested that the use of age-specific PSA reference ranges may increase the accuracy of PSA tests. However, age-specific reference ranges have not been generally favored because their use may delay the detection of prostate cancer in many men.
• PSA velocity and PSA doubling time. PSA velocity is the rate of change in a man’s PSA level over time, expressed as ng/mL per year. PSA doubling time is the period of time over which a man’s PSA level doubles. Some evidence suggests that the rate of increase in a man’s PSA level may be helpful in predicting whether he has prostate cancer.  
• Pro-PSA. Pro-PSA refers to several different inactive precursors of PSA. There is some evidence that pro-PSA is more strongly associated with prostate cancer than with BPH. One recently approved test combines measurement of a form of pro-PSA called [-2]proPSA with measurements of PSA and free PSA. The resulting “prostate health index” can be used to help a man with a PSA level of between 4 and 10 ng/mL decide whether he should have a biopsy.
• IsoPSA. PSA exists in different structural forms (called isoforms) in the blood. The IsoPSA test, which measures the entire spectrum of PSA isoforms rather than the concentration of PSA in the blood, may improve the selection of men with prostate cancer for biopsy.⁸
• PSA in combination with other protein biomarkers.  Tests that combine measurements of PSA in blood with measurements of other biomarkers linked to prostate cancer in blood or urine are being studied for their ability to distinguish high-risk disease. These other biomarkers include kallikrein-related peptidase 2, prostatecancer antigen 3 (PCA3), and the TMPRSS2-ERG gene fusion.

Selected References

1. Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. New England Journal of Medicine 2004;350(22):2239-2246. [PubMed Abstract]
2. Barry MJ. Clinical practice. Prostate-specific-antigen testing for early diagnosis of prostate cancer. New England Journal of Medicine 2001;344(18):1373-1377. [PubMed Abstract]
3. Pinsky PF, Prorok PC, Yu K, et al. Extended mortality results for prostate cancer screening in the PLCO trial with median follow-up of 15 years. Cancer 2017; 123(4):592-599. [PubMed Abstract]
4. Schröder FH, Hugosson J, Roobol MJ, et al. Prostate-cancer mortality at 11 years of follow-up. New England Journal of Medicine 2012;366(11):981-990. [PubMed Abstract]
5. Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate cancer mortality: Results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014; 384: 2027-2035. [PubMed Abstract]
6. Tsodikov A, Gulati R, Heijnsdijk EAM, et al. Reconciling the effects of screening on prostate cancer mortality in the ERSPC and PLCO trials. Annals of Internal Medicine2017; 167(7):449-455. [PubMed Abstract]
7. U.S. Preventive Health Services Task Force. Prostate Cancer Screening Draft RecommendationsExit Disclaimer. 2017. Accessed April 24, 2017.
8. Klein EA, Chait A, Hafron JM, et al. The single-parameter, structure-based IsoPSA assay demonstrates improved diagnostic accuracy for detection of any prostate cancer and high-grade prostate cancer compared to a concentration-based assay of total prostate-specific antigen: A preliminary report. European Urology 2017; S0302-2838(17)30236-1. [PubMed Abstract]

Source: National Cancer Institute.

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