Current State of Prostate Cancer Testing

Prostate cancer is one of the leading causes of cancer related mortality among men in the United States.¹ Early detection and new treatments have been attributed to the excellent five-year survival rate is excellent (98.9%), however this statistic considerably decreases when metastasis is involved (28.5%).² Screening serves as the mainstay to enable early recognition of prostate cancer. Two tests have been used to screen for prostate cancer: (a) digital rectal exam (DRE) for determining prostate size and detect lumps or other abnormalities, and (b) prostate specific antigen (PSA) testing.³ For this month’s Laboratory Best Practice blog, we will focus on prostate cancer biomarkers including PSA testing.

The use of PSA for screening unfortunately remains a controversial topic.⁴ Typically, blood PSA levels are higher in men who have prostate cancer. However, PSA levels may also be elevated in other conditions affecting the prostate (e.g., trauma, infection, age, medication [5 alpha-reductase inhibitor])—potentially leading to false positive results.^5,6 False negative results are also possible where PSA levels are below screening cut offs despite the presence of prostate cancer. To this end, PSA performance as a cancer biomarker can mean some men without cancer may have abnormal results and be followed with unnecessary tests and/or procedures; or alternately, PSA may miss cancer in men who require treatment.

Lab best practice

Guidelines from the American College of Physicians⁷, American Cancer Society⁸, American Urological Association⁹, US Preventive Services Task Force⁴, American Society of Clinical Oncology¹⁰ uniformly recommend encouraging patients to make informed decisions about screening that reflects personal preferences and values. Where consensus may be lacking, recommendations from specific groups support performing DRE and measuring PSA levels, while other groups question the benefit of frequent testing using these methodologies.^4,7-10 In practice, patients with age of 50 to 75 years, men >45 years old with history of one first degree family of prostate cancer before the age of 65 years or African-American men, and men over 40 years old with history of two first degree family of prostate cancer before the age of 65 years or with BRCA 1/2 gene mutation may benefit from routine screening.

Healthcare providers should also be aware of the differences in analytical performance between PSA assays¹¹—especially those performed manually. Modern laboratories predominantly utilize automated PSA platforms; however, some facilities continue to employ manual methods. Regardless of manual or automated methods, the variability for all PSA assays remains less than ideal despite attempts by the World Health Organization to standardize biomarker testing. To mitigate these performance issues, it is recommended that laboratories report the specific platform (name of manufacturer and instrument) in their test reports, and providers should be aware that results from different platforms are not interchangeable. In addition to the analytical (instrument-specific) variability of PSA, the biological variability of the biomarker is high.¹² A study showed year-to-year PSA fluctuations to be as high as 44% in men with PSA concentrations >4 ng/mL. These patients were found to have a normal follow-up PSA one year later. Based on these findings, it is recommended that patients with PSA between 4 and 7 ng/mL undergo repeat testing several weeks later, however, it must be noted that the analytical and biological variability of PSA assays create a diagnostic “gray zone” for values between 4.0 and 10.0 ng/mL.¹²¹³ In these cases, calculation of the free:total PSA ratio may also help identify the relative risk of prostate cancer. Ultimately, like with any other test, the diagnosis of disease should not be based on a single biomarker (including those discussed below), but also be evaluated in proper clinical context. Normal PSA results do not exclude the possibility of prostate cancer and tumor markers are not specific for malignancy.

Other Biomarkers for Prostate Cancer

New prostate cancer biomarkers have been proposed (Table 1)^14-16, however, there have not been a suitable cost-effective replacement for PSA. For example, trans-rectal biopsy is invasive and the use of magnetic resonance imaging expensive for mass screening. Genomic profiling may allow characterization of high-risk patients early on. These new assays, coupled with advances in imaging and biopsy techniques, should help advance our diagnostic strategy. Unfortunately, many of the methods described on Table 1 are proprietary and/or require specific testing platforms that may not be available at all institutions.

Table 1. Alternate Prostate Cancer Tests

Prostate Specific Antigen Antibody https://www.celnovte.com/prostate-specific-antigen-psa/

PTEN Antibody : https://www.celnovte.com/pten/

PTEN Probe: https://www.celnovte.com/pten-gene-detection-kit/

ERG Probe: https://www.celnovte.com/erg-gene-rearrangement-detection-kit/

References

1. S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2014 Incidence and Mortality Web-based Report.Atlanta (GA): Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute; 2017.
2. American Cancer Society Facts and Figures: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2017/cancer-facts-and-figures-2017.pdf, Accessed on April 11, 2018.
3. Carroll P, Coley C, McLeod D, et al. Prostate-specific antigen best practice policy–part I: early detection and diagnosis of prostate cancer. Urology 2001;57:217.
4. United States Preventive Services Task Force website: https://www.uspreventiveservicestaskforce.org/ Page/Document/UpdateSummaryFinal/prostate-cancer-screening, Accessed on April 11, 2018.
5. Jacobsen SJ, Bergstralh EJ, Guess HA, et al: Predictive properties of serum prostate-specific antigen testing in a community-based setting. Arch Intern Med 1996;156:2462-2468
6. Oesterling JE, Jacobsen SJ, Chute CG, et al: Serum prostate-specific antigen in a community-based population of healthy men. JAMA 1993;270:860-864.
7. Qaseem A, Barry MJ, Denberg TD, et al. Screening for prostate cancer: a guidance statement from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2013;158(10):761.
8. Wolf AM, Wender RC, Etzioni RB, et al. American Cancer Society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin. 2010;60(2):70.
9. American Urological Association website:
   auanet.org/education/guidelines/prostate-cancer-detection.cfm, Accessed on April 11, 2018
10. Basch E, Oliver TK, Vickers A, et al. Screening for prostate cancer with prostate-specific antigen testing: American Society of Clinical Oncology Provisional Clinical Opinion. J Clin Oncol. 2012;30(24):3020
11. Blasé AB, Sokoloff RL, Smith KM. Five PSA methods compared by assaying samples with defined PSA ratios. Clin Chem 1997;43:843-845.
12. Nixon RG, Wener MH, Smith KM, et al. Biological variation of prostate specific antigen levels in serum: an evaluation of day-to-day physiological fluctuations in a well-defined cohort of 24 patients. J Urol 1997;157(6):2183-90
13. Jung K, Elgeti U, Lein M, et al. Ratio of free or complexed prostate-specific antigen (PSA) to total PSA: which ratio improves differentiation between benign prostatic hyperplasia and prostate cancer? Clin Chem. 2000;46(1):55-62.
14. Gaudreau et al. The Present and Future of Biomarkers in Prostate Cancer: Proteomics, Genomics, and Immunology Advancements. Biomarkers in Cancer. 2016;8(Suppl 2):15-33.
15. Jakobsen NA, Hamdy FC, Bryant RJ. Novel biomarkers for the detection of prostate cancer. J Clin Urol. 2016;9(2 Suppl):3-10.
16. Saini S. PSA and beyond: alternative prostate cancer biomarkers. Cellular oncology (Dordrecht). 2016;39(2):97-106.

    This article from https://health.ucdavis.edu/blog/lab-best-practice/current-state-of-prostate-cancer-testing/2018/04

Contact us info@celnovte-bio-tech.com