How is prostate specific antigen measured. What factors can affect PSA levels. When should PSA screening begin. How accurate is PSA testing for prostate cancer detection. What are the limitations of PSA testing. How are PSA results interpreted by doctors. What follow-up is needed for elevated PSA levels.

The Discovery and Development of PSA Testing

Prostate Specific Antigen (PSA) has revolutionized the field of prostate cancer screening and management since its discovery in 1979. But how did this crucial biomarker come to be such an integral part of men’s health?

Wang et al. first purified PSA from human prostate tissue in 1979, marking the beginning of a new era in prostate cancer detection. This groundbreaking work laid the foundation for the development of PSA as a serum marker for prostate cancer, which was later established by Stamey et al. in 1987.

The clinical significance of PSA testing became apparent in 1991 when Catalona et al. demonstrated its effectiveness as a screening tool for prostate cancer. This study paved the way for widespread adoption of PSA testing in clinical practice.

The Evolution of PSA Testing Methods

As PSA testing gained prominence, researchers worked to refine measurement techniques. Myrtle and Ivor developed two immunometric methods for measuring PSA in serum: the Hybritech Tandem-R and Tandem-E PSA assays. These methods improved the accuracy and reliability of PSA measurements, further cementing its role in prostate cancer screening.

Understanding PSA Levels and Their Significance

PSA levels are typically measured in nanograms per milliliter (ng/mL) of blood. But what do these numbers actually mean? Traditionally, a PSA level below 4.0 ng/mL was considered normal, while levels above this threshold warranted further investigation.

However, research has shown that interpreting PSA levels is not as straightforward as once thought. Thompson et al. found that prostate cancer can occur in men with PSA levels below 4.0 ng/mL, challenging the notion of a clear-cut “normal” range.

Factors Affecting PSA Levels

• Age: PSA levels tend to increase naturally with age
• Prostate size: Larger prostates may produce more PSA
• Inflammation or infection: Conditions like prostatitis can elevate PSA
• Certain medications: Some drugs, like finasteride, can affect PSA levels
• Recent ejaculation or prostate stimulation

Given these various influences, how can healthcare providers accurately interpret PSA results? The answer lies in considering multiple factors and not relying solely on a single PSA measurement.

The Controversy Surrounding PSA Screening

Despite its widespread use, PSA screening has been the subject of intense debate within the medical community. Why is this potentially life-saving test so controversial?

The crux of the issue lies in the balance between the potential benefits of early detection and the risks of overdiagnosis and overtreatment. Several large-scale studies have attempted to shed light on this complex issue:

1. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial in the United States
2. The European Randomized Study of Screening for Prostate Cancer (ERSPC)
3. The Göteborg randomized population-based prostate-cancer screening trial

These studies have produced conflicting results, further fueling the debate. The PLCO trial found no significant reduction in prostate cancer mortality with PSA screening, while the ERSPC and Göteborg trials showed a modest benefit.

The Impact of PSA Screening on Prostate Cancer Mortality

Interestingly, despite the controversy, prostate cancer mortality rates have shown a declining trend in several countries. Bouchardy et al. and Kvåle et al. have documented this decrease, suggesting that PSA screening may be having a positive impact on overall outcomes.

However, the question remains: does this reduction in mortality outweigh the potential harms of overdiagnosis and overtreatment? This delicate balance continues to be a subject of ongoing research and debate.

PSA Testing in the Context of Benign Prostatic Hyperplasia (BPH)

BPH, a common condition in older men, can complicate the interpretation of PSA results. How does BPH affect PSA levels, and what implications does this have for prostate cancer screening?

Atan et al. found that BPH can indeed elevate PSA levels, potentially leading to false-positive results in prostate cancer screening. This underscores the importance of considering other factors, such as prostate size and symptoms, when interpreting PSA results.

Differentiating Between BPH and Prostate Cancer

Given the potential overlap in PSA levels between BPH and prostate cancer, additional diagnostic tools are often necessary. These may include:

• Digital rectal examination (DRE)
• Free PSA ratio
• PSA density
• PSA velocity
• Prostate imaging (e.g., MRI)
• Prostate biopsy

By combining these methods with PSA testing, healthcare providers can more accurately distinguish between benign conditions and potential malignancies.

The Role of Shared Decision-Making in PSA Testing

Given the complexities and controversies surrounding PSA testing, how can patients and healthcare providers navigate this challenging landscape? The answer lies in shared decision-making.

Woolf and Krist emphasize the importance of involving patients in the decision to undergo PSA screening. This approach takes into account individual risk factors, personal preferences, and the potential benefits and harms of screening.

Key Elements of Shared Decision-Making in PSA Testing

• Educating patients about prostate cancer risk factors
• Discussing the pros and cons of PSA screening
• Considering individual values and preferences
• Addressing concerns and answering questions
• Collaboratively deciding on the best course of action

By engaging in this process, patients can make informed decisions that align with their personal health goals and values.

Emerging Trends in PSA Testing and Prostate Cancer Screening

As our understanding of prostate cancer and PSA biology continues to evolve, new approaches to screening and risk assessment are emerging. What are some of the latest developments in this field?

Stricker et al. propose a risk-adjusted testing paradigm that takes into account multiple factors beyond just PSA levels. This approach aims to improve the accuracy of prostate cancer detection while reducing unnecessary biopsies and treatments.

Novel Biomarkers and Screening Strategies

Researchers are actively investigating new biomarkers and screening strategies to complement or potentially replace traditional PSA testing. Some promising avenues include:

• Prostate Health Index (PHI)
• 4Kscore Test
• PCA3 urine test
• Multiparametric MRI
• Genetic risk scores

These emerging tools may help to further refine prostate cancer risk assessment and guide treatment decisions more effectively.

The Future of PSA Testing and Prostate Cancer Management

As we look to the future, what can we expect in the realm of PSA testing and prostate cancer management? While it’s impossible to predict with certainty, several trends are likely to shape the field:

1. Increased use of risk-stratified screening approaches
2. Integration of novel biomarkers and imaging techniques
3. Greater emphasis on active surveillance for low-risk cancers
4. Continued refinement of treatment algorithms
5. Ongoing research into the biology of prostate cancer and PSA

These developments hold the promise of more personalized and effective prostate cancer screening and management strategies.

The Importance of Ongoing Research and Education

As the landscape of PSA testing and prostate cancer management continues to evolve, ongoing research and education are crucial. Healthcare providers must stay informed about the latest developments and guidelines to provide the best possible care to their patients.

Equally important is patient education. By empowering men with knowledge about PSA testing, prostate cancer risk factors, and screening options, we can foster more informed decision-making and ultimately improve outcomes.

Interpreting PSA Results: A Nuanced Approach

Given the complexities surrounding PSA testing, how should healthcare providers interpret PSA results? The answer lies in taking a nuanced, multifaceted approach that considers various factors beyond just the PSA number.

Greene et al. provide a comprehensive best practice statement for PSA interpretation, emphasizing the importance of considering age, prostate volume, PSA velocity, and other clinical factors when assessing PSA results.

Key Considerations in PSA Interpretation

• Age-specific PSA reference ranges
• Free PSA ratio
• PSA density (PSA level relative to prostate volume)
• PSA velocity (rate of change over time)
• Presence of other risk factors (e.g., family history, race)
• Overall health status and life expectancy

By taking these factors into account, healthcare providers can make more informed decisions about the need for further testing or intervention.

The Limitations of PSA Testing

While PSA testing has undoubtedly improved prostate cancer detection, it’s crucial to recognize its limitations. What are some of the key drawbacks of PSA testing?

1. False positives: Elevated PSA levels can occur in benign conditions
2. False negatives: Some aggressive cancers may not produce elevated PSA
3. Overdiagnosis: Detection of indolent cancers that may never cause harm
4. Anxiety and psychological distress associated with abnormal results
5. Potential complications from follow-up procedures (e.g., biopsies)

Understanding these limitations is crucial for both healthcare providers and patients when making decisions about PSA testing and follow-up care.

PSA Testing in Special Populations

While general guidelines for PSA testing exist, certain populations may require special consideration. How should PSA testing be approached in these groups?

African American Men

African American men have a higher risk of developing and dying from prostate cancer. As such, some guidelines recommend earlier and more frequent PSA screening for this population. Healthcare providers should discuss this increased risk and the potential benefits of earlier screening with African American patients.

Men with a Family History of Prostate Cancer

Men with a first-degree relative (father, brother, or son) diagnosed with prostate cancer are at increased risk. For these individuals, PSA screening may be recommended at an earlier age, typically starting at 40-45 years old.

Older Men

The benefits of PSA screening in older men, particularly those over 70, are less clear. Life expectancy and overall health status should be carefully considered when making decisions about PSA testing in this population.

Men with Previous Negative Biopsies

For men who have had previous negative biopsies but persistently elevated PSA levels, additional considerations may be necessary. Van Renterghem et al. propose an algorithm for managing these challenging cases, which may involve additional biomarker testing or imaging studies.

The Role of PSA in Treatment Monitoring and Follow-up

Beyond its use in screening, PSA plays a crucial role in monitoring treatment response and detecting recurrence in men with prostate cancer. How is PSA used in this context?

Post-Treatment PSA Monitoring

After definitive treatment (e.g., surgery or radiation), PSA levels are expected to fall to very low or undetectable levels. Regular PSA testing is used to monitor for potential recurrence, with any rise in PSA potentially indicating disease progression.

PSA in Advanced Prostate Cancer

In men with advanced or metastatic prostate cancer, PSA levels can help guide treatment decisions and assess response to therapy. Mottet et al. provide guidelines for managing advanced prostate cancer, including the role of PSA monitoring.

PSA Doubling Time

PSA doubling time, or the rate at which PSA levels increase, can provide valuable information about the aggressiveness of prostate cancer. Rapid PSA doubling times may indicate more aggressive disease and the need for more intensive treatment.

By carefully monitoring PSA levels throughout the course of treatment and follow-up, healthcare providers can make more informed decisions about patient care and potentially improve outcomes.

Ethical Considerations in PSA Testing and Prostate Cancer Screening

The use of PSA testing for prostate cancer screening raises several ethical questions. How do we balance the potential benefits of early detection with the risks of overdiagnosis and overtreatment?

The Principle of Non-Maleficence

The principle of “first, do no harm” is fundamental to medical ethics. In the context of PSA testing, this principle requires careful consideration of the potential harms associated with screening, including unnecessary anxiety, invasive procedures, and treatment-related side effects.

Autonomy and Informed Consent

Respecting patient autonomy is crucial in the decision to undergo PSA testing. This involves providing comprehensive information about the risks and benefits of screening, as well as respecting the patient’s right to make an informed decision.

Justice and Resource Allocation

From a public health perspective, the widespread use of PSA screening raises questions about resource allocation. How do we ensure equitable access to screening while also considering the cost-effectiveness of these programs?

Addressing these ethical considerations requires ongoing dialogue between healthcare providers, policymakers, and the public to ensure that PSA testing is used in a way that maximizes benefits and minimizes harms.

The Global Perspective on PSA Testing and Prostate Cancer Screening

Prostate cancer is a global health concern, but approaches to screening and PSA testing vary widely across different countries and healthcare systems. What factors influence these variations, and what can we learn from different approaches?

Variations in Screening Guidelines

Different countries and medical organizations have developed varying guidelines for PSA screening. These differences reflect not only variations in healthcare systems and resources but also differing interpretations of the available evidence.

Cultural and Socioeconomic Factors

Cultural attitudes towards preventive healthcare, as well as socioeconomic factors, can significantly influence the uptake and implementation of PSA screening programs. Understanding these factors is crucial for developing effective, culturally sensitive screening strategies.

The Impact of Healthcare Systems

The structure and funding of healthcare systems can greatly affect the availability and utilization of PSA testing. Some countries have implemented organized screening programs, while others rely on opportunistic screening during routine healthcare visits.

By examining these global perspectives, we can gain valuable insights into the strengths and limitations of different approaches to PSA testing and prostate cancer screening.

How should prostate specific antigen be interpreted?

1. Wang MC, Valenzuela LA, Murphy GP, Chu TM. Purification of a human prostate specific antigen. Invest Urol. 1979;17:159–63. [PubMed] [Google Scholar]

2. Venderbos LD, Roobol MJ. PSA-based prostate cancer screening: the role of active surveillance and informed and shared decision making. Asian J Androl. 2011;13:219–24. [PMC free article] [PubMed] [Google Scholar]

3. Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med. 1987;317:909–16. [PubMed] [Google Scholar]

4. Catalona WJ, Smith DS, Ratliff TL, Dodds KM, Coplen DE, Yuan JJ, et al. Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med. 1991;324:1156–61. [PubMed] [Google Scholar]

5. Woolf SH, Krist A. Shared decision making for prostate cancer screening: do patients or clinicians have a choice? Arch Intern Med. 2009;169:1557–9. [PubMed] [Google Scholar]

6. Myrtle J, Ivor L. Measurement of PSA in Serum by two immunometric Methods (Hybritech Tandem-R/Tandem-E PSA). In: Catalona WJ, editor. Clinical Aspects of Prostate Cancer. New York: Elsevier; 1989. pp. 161–71. [Google Scholar]

7. Gjertson CK, Albertsen PC. Use and assessment of PSA in prostate cancer. Med Clin North Am. 2011;95:191–200. [PubMed] [Google Scholar]

8. Greene KL, Albertsen PC, Babaian RJ, Carter HB, Gann PH, Han M, et al. Prostate specific antigen best practice statement: 2009 update. J Urol. 2013;189:2–11. [PubMed] [Google Scholar]

9. Atan A, Horn T, Hansen F, Jakobsen H, Hald T. Prostatic specific antigen and benign prostatic hyperplasia. Scand J Urol Nephrol. 1996;30:299–302. [PubMed] [Google Scholar]

10. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300. [PubMed] [Google Scholar]

11. Mettlin C, Murphy GP, Lee F, Littrup PJ, Chesley A, Babaian R, et al. Characteristics of prostate cancers detected in a multimodality early detection program. The Investigators of the American Cancer Society-National Prostate Cancer Detection Project. Cancer. 1993;72:1701–8. [PubMed] [Google Scholar]

12. Catalona WJ. Treatment strategies for prostate cancer. JAMA. 1993;270:1691. [PubMed] [Google Scholar]

13. Mottet N, Bellmunt J, Bolla M, Joniau S, Mason M, Matveev V, et al. EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2011;59:572–83. [PubMed] [Google Scholar]

14. van Renterghem K, Van Koeveringe G, Achten R, van Kerrebroeck P. A new algorithm in patients with elevated and/or rising prostate-specific antigen level, minor lower urinary tract symptoms, and negative multisite prostate biopsies. Int Urol Nephrol. 2010;42:29–38. [PMC free article] [PubMed] [Google Scholar]

15. Gjertson CK, Albertsen PC. Use and assessment of PSA in prostate cancer. Med Clin North Am. 2011;95:191–200. [PubMed] [Google Scholar]

16. Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med. 2004;350:2239–46. [PubMed] [Google Scholar]

17. Andriole GL, Crawford ED, Grubb RL, 3rd, Buys SS, Chia D, Church TR, et al.PLCO Project Team. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310–9. [PMC free article] [PubMed] [Google Scholar]

18. Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al.ERSPC Investigators. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320–8. [PubMed] [Google Scholar]

19. Sandblom G, Varenhorst E, Rosell J, Löfman O, Carlsson P. Randomised prostate cancer screening trial: 20 year follow-up. BMJ. 2011;342:1539. [PMC free article] [PubMed] [Google Scholar]

20. Hugosson J, Carlsson S, Aus G, Bergdahl S, Khatami A, Lodding P, et al. Mortality results from the Göteborg randomised population-based prostate-cancer screening trial. Lancet Oncol. 2010;11:725–32. [PMC free article] [PubMed] [Google Scholar]

21. Stricker PD, Frydenberg M, Kneebone A, Chopra S. Informed prostate cancer risk-adjusted testing: a new paradigm. BJU Int. 2012;110:30–4. [PubMed] [Google Scholar]

22. Bouchardy C, Fioretta G, Rapiti E, Verkooijen HM, Rapin CH, Schmidlin F, et al. Recent trends in prostate cancer mortality show a continuous decrease in several countries. Int J Cancer. 2008;123:421–9. [PubMed] [Google Scholar]

23. Kvåle R, Auvinen A, Adami HO, Klint A, Hernes E, Møller B, et al. Interpreting trends in prostate cancer incidence and mortality in the five Nordic countries. J Natl Cancer Inst. 2007;99:1881–7. [PubMed] [Google Scholar]

24. van Leeuwen PJ, Connolly D, Gavin A, Roobol MJ, Black A, Bangma CH, et al. Prostate cancer mortality in screen and clinically detected prostate cancer: estimating the screening benefit. Eur J Cancer. 2010;46:377–83. [PubMed] [Google Scholar]

25. Draisma G, Etzioni R, Tsodikov A, Mariotto A, Wever E, Gulati R, et al. Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. J Natl Cancer Inst. 2009;101:374–83. [PMC free article] [PubMed] [Google Scholar]

26. Heidenreich A, Bellmunt J, Bolla M, Joniau S, Mason M, Matveev V, et al.European Association of Urology EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Eur Urol. 2011;59:61–71. [PubMed] [Google Scholar]

27. Steyerberg EW, Roobol MJ, Kattan MW, van der Kwast TH, de Koning HJ, Schröder FH. Prediction of indolent prostate cancer: validation and updating of a prognostic nomogram. J Urol. 2007;177:107–12. [PubMed] [Google Scholar]

28. Welch HG, Albertsen PC. Prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening: 1986–2005. J Natl Cancer Inst. 2009;101:1325–9. [PMC free article] [PubMed] [Google Scholar]

29. Mouraviev V, Madden JF. Focal therapy for prostate cancer: pathologic basis. Curr Opin Urol. 2009;19:161–7. [PubMed] [Google Scholar]

30. Hayes JH, Ollendorf DA, Pearson SD, Barry MJ, Kantoff PW, Stewart ST, et al. Active surveillance compared with initial treatment for men with low-risk prostate cancer: a decision analysis. JAMA. 2010;304:2373–80. [PMC free article] [PubMed] [Google Scholar]

31. D’Amico AV, Whittington R, Malkowicz SB, Fondurulia J, Chen MH, Kaplan I, et al. Pretreatment nomogram for prostate-specific antigen recurrence after radical prostatectomy or external-beam radiation therapy for clinically localized prostate cancer. J Clin Oncol. 1999;17:168–72. [PubMed] [Google Scholar]

32. Wolf AM, Wender RC, Etzioni RB, Thompson IM, D’Amico AV, Volk RJ, et al.American Cancer Society Prostate Cancer Advisory Committee. American Cancer Society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin. 2010;60:70–98. [PubMed] [Google Scholar]

33. Calonge N, Petitti DB, DeWitt TG, Dietrich AJ, Gregory KD, Harris R, et al.U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149:185–91. [PubMed] [Google Scholar]

34. Kawachi MH, Bahnson RR, Barry M, Busby JE, Carroll PR, Carter HB, et al. NCCN clinical practice guidelines in oncology: prostate cancer early detection. J Natl Compr Canc Netw. 2010;8:240–62. [PubMed] [Google Scholar]

35. Zhu X, Albertsen PC, Andriole GL, Roobol MJ, Schröder FH, Vickers AJ. Risk-based prostate cancer screening. Eur Urol. 2012;61:652–61. [PMC free article] [PubMed] [Google Scholar]

36. Loeb S, Roehl KA, Antenor JA, Catalona WJ, Suarez BK, Nadler RB. Baseline prostate-specific antigen compared with median prostate-specific antigen for age group as predictor of prostate cancer risk in men younger than 60 years old. Urology. 2006;67:316–20. [PubMed] [Google Scholar]

37. McConnell JD, Bruskewitz R, Walsh P, Andriole G, Lieber M, Holtgrewe HL, et al. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group. N Engl J Med. 1998;338:557–63. [PubMed] [Google Scholar]

38. Roehrborn CG, Boyle P, Gould AL, Waldstreicher J. Serum prostate-specific antigen as a predictor of prostate volume in men with benign prostatic hyperplasia. Urology. 1999;53:581–9. [PubMed] [Google Scholar]

39. Mochtar CA, Kiemeney LA, van Riemsdijk MM, Barnett GS, Laguna MP, Debruyne FM, et al. Prostate-specific antigen as an estimator of prostate volume in the management of patients with symptomatic benign prostatic hyperplasia. Eur Urol. 2003;44:695–700. [PubMed] [Google Scholar]

40. Crawford ED, Wilson SS, McConnell JD, Slawin KM, Lieber MC, Smith JA, et al.MTOPS RESEARCH Group. Baseline factors as predictors of clinical progression of benign prostatic hyperplasia in men treated with placebo. J Urol. 2006;175:1422–7. [PubMed] [Google Scholar]

41. Laniado ME, Ockrim JL, Marronaro A, Tubaro A, Carter SS. Serum prostate-specific antigen to predict the presence of bladder outlet obstruction in men with urinary symptoms. BJU Int. 2004;94:1283–6. [PubMed] [Google Scholar]

42. Bantis A, Zissimopoulos A, Kalaytzis C, Giannakopoulos S, Sountoulides P, Agelonidou E, et al. Correlation of serum prostate specific antigen, the volume and the intravesical prostatic protrusion for diagnosing bladder outlet obstruction in patients with benign prostate hyperplasia. Hell J Nucl Med. 2007;10:138–43. [PubMed] [Google Scholar]

43. Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G, ARIA3001 ARIA3002 and ARIA3003 Study Investigators. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology. 2002;60:434–41. [PubMed] [Google Scholar]

44. Bartsch G, Fitzpatrick JM, Schalken JA, Isaacs J, Nordling J, Roehrborn CG. Consensus statement: the role of prostate-specific antigen in managing the patient with benign prostatic hyperplasia. BJU Int. 2004;93:27–9. [PubMed] [Google Scholar]

45. Madersbacher S, Alivizatos G, Nordling J, Sanz CR, Emberton M, de la Rosette JJ. EAU 2004 guidelines on assessment, therapy and follow-up of men with lower urinary tract symptoms suggestive of benign prostatic obstruction (BPH guidelines) Eur Urol. 2004;46:547–54. [PubMed] [Google Scholar]

46. Tuncel A, Aksut H, Agras K, Tekdogan U, Ener K, Atan A. Is serum prostate-specific antigen level affected by fasting and nonfasting? Urology. 2005;66:105–7. [PubMed] [Google Scholar]

High PSA, No Prostate Cancer: Understand Your Results

You may have elevated PSA levels due to age or certain health conditions, including an enlarged prostate and certain infections.

Prostate-specific antigen (PSA) is a protein produced by prostate gland cells. Elevated levels may indicate prostate cancer, but PSA levels can also be affected by other things, such as enlarged prostate, a urinary tract infection, or recent ejaculation.

On their own, PSA levels aren’t a good indicator of prostate health. Instead, your doctor will look at your PSA levels alongside other risk factors, like age, digital rectal exam results, and family history. Keep reading to learn more about why your PSA levels may be high.

PSA levels may increase as you get older. This normal rise may be caused by the growth of benign, prostatic tissue. Some men also experience an enlarging of their prostate as they age, which may also elevate PSA levels.

BPH, also known as enlarged prostate, is common in older men. BPH can raise PSA levels and affect the bladder and urinary tract. Men with BPH may have difficulty urinating. If left untreated, it may also interfere with kidney function.

Common symptoms include:

• difficulty initiating urination
• weak urine output, which includes dribbling or straining, or stops and starts during urination
• frequent urination
• urgent need to urinate
• Inability to empty bladder completely

The prostate enlarges in many men as they age, possibly as a result of shifting hormonal levels. BPH only requires treatment if symptoms are affecting quality of life or health. Treatments include medications, such as alpha blockers or 5-alpha reductase inhibitors. If your symptoms are severe or do not respond to medication, a minimally-invasive surgical procedure or laser therapy may help to alleviate the problem.

Learn more: Traditional treatment methods for enlarged prostate »

UTIs may spike PSA levels. They are commonly diagnosed through a urine test and treated with antibiotics. Symptoms of a UTI include:

• a constant urge to urinate, which is not always fully relieved after urination
• inability to fully relieve the bladder
• lower back pain, particularly in the flank
• abdominal pain
• a burning sensation or pain during urination
• cloudy, foul smelling, or bloody urine
• fevers or chills

UTIs become more common as you age. Some men are also at greater risk for UTIs. Risk factors include having:

• diabetes
• kidney stones
• an enlarged prostate
• a compromised immune system

Talk to your doctor if you think you have a UTI. They are often treated with antibiotics. If you have high PSA levels and a known UTI, you will need to wait until you’ve recovered from your UTI before repeating the PSA test.

A common condition in men under 50, prostatitis is often the result of a bacterial infection. It causes swelling, inflammation, and irritation of the prostate gland. Symptoms are similar to those of a UTI, and may include:

• lower back or abdominal pain
• pain or discomfort when urinating
• difficulty urinating

If bacterial infection is causing your prostatitis, you may also experience flu-like symptoms and be treated with antibiotics. Nerve damage in the urinary tract may also cause prostatitis. This can occur as a result of injury or as a surgical complication. If no infection is found, anti-inflammatory medication or alpha-blockers may be used to reduce discomfort.

Some studies have looked at the effects of ejaculation on PSA levels. One study published in 2016 found that PSA levels rise in some men after ejaculation. They may remain higher than their typical baseline level for up to 24 hours afterward.

More research is needed to fully understand the effects of ejaculation on PSA levels. However, if you have a PSA test scheduled, consider abstaining from sexual activities that may result in ejaculation for 24 hours before the test.

Parathyroid hormone is naturally occurring hormone produced by the body to regulate calcium levels in the blood. It may also promote prostate cancer cell growth, even in men who do not have prostate cancer. For this reason, high levels of parathyroid hormone may escalate PSA levels.

An injury to the groin, caused by a fall, impact, or accident, may spike PSA levels temporarily. Let your doctor know if you suspect an injury may have affected your PSA levels.

Any procedure that causes temporary bruising or trauma to the groin can have an effect on PSA levels. This can include the insertion of any type of instrument, such as a catheter or surgical scope, into the bladder.

Prostate cancer can cause your PSA levels to increase, so your doctor may recommend that you get a PSA blood test in conjunction with other tests, such as a digital rectal exam, to assess your potential risk. Doctors often recommend PSA testing in men 50 and older. Your doctor may recommend testing your levels at an earlier age if you have known risk factors for prostate cancer, like family history of the disease.

If your PSA levels are high and other diagnostic tests also indicate an increased risk for prostate cancer, your doctor will likely recommend a biopsy to confirm a prostate cancer diagnosis. Ask your doctor about all of the risks associated with biopsy. For some men, holding off on a biopsy and taking a watchful approach is a good option because prostate cancer is generally slow growing. Your doctor will go over all of your options and explain the risks associated with each option.

Second opinion

Getting a second medical opinion can help put your mind at ease about your current care or give you a different perspective, which may help you to decide upon your best options for treatment.

If your current doctor recommends PSA testing or further testing or biopsy after a PSA test, make sure to discuss the benefits versus the risks of each procedure being recommended. Take notes or bring someone with you to your appointment to take notes for you. If you feel the need to discuss this information with another doctor, you absolutely should.

It’s important to remember that elevated PSA levels can mean many things. Prostate cancer is one of those things. If it feels medically necessary to have a biopsy or other testing done, make sure to weigh the benefits versus the risks of each test. Prostate cancer, especially when caught early, is treatable. So are many of the other causes of elevated PSA.

A:

Answers represent the opinions of our medical experts. All content is strictly informational and should not be considered medical advice.

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General prostate-specific antigen (General PSA)

General prostate-specific antigen – this is the amount in the blood available for determination of the fractions of the substance that is part of the secretion of the prostate gland – serine protease. Prostate-specific antigen is a laboratory marker of the condition of the prostate tissue.

Synonyms Russian

General prostate specific antigen, prostate cancer marker.

Synonyms English

Prostate-specific antigen total, PSA total.

Test method

Immunochemiluminescent assay.

Detection range: 0.006 – 5000 ng/ml.

Units

Ng/mL (nanograms per milliliter).

What biomaterial can be used for research?

Venous blood.

How to properly prepare for an examination?

• Eliminate fatty foods for 24 hours before the test.
• Patients treated with high doses of biotin (> 5 mg/day) should be sampled no sooner than 8 hours after their last dose.
• Avoid physical and emotional stress for 30 minutes prior to examination.
• Do not smoke for 30 minutes before the test.
• Examination should be carried out no earlier than 10 days after prostate massage (obtaining prostate secretion, seminal vesicle massage).

General information about the study

Prostate-specific antigen (PSA) is a protein substance, an enzyme belonging to serine proteases. It is one of the synthesis products of the prostate gland.

The prostate gland consists of muscle tissue and a large number (about 50) of small glands. Muscle tissue is designed to move the fluid that the prostate produces into the internal ducts towards the lumen of the urethra. In addition, intense contractions of the prostate muscles provide the process of ejaculation during intercourse.

The prostate glands produce prostate secretion, which has several functions: it is part of the seminal fluid and serves as an important component of the nutrient medium for spermatozoa. This is a complex composition of biologically active substances that ensure the vital activity of male germ cells. A small part of the secret enters the bloodstream and performs a complex hormonal function – it ensures the normal functioning of the testicles, the functioning of the bladder, regulates sexual desire, affects blood circulation, nervous processes and mental state.

One of the components of prostate secretion is PSA. According to its chemical structure, it is a glycoprotein – a combination of protein and carbohydrates, according to biochemical properties – an enzyme that performs the function of splitting large protein molecules into smaller fragments. Thanks to this ability, it dilutes the seminal fluid. Together with that part of the secretion of the prostate gland that enters the systemic circulation, a small portion of the prostate-specific antigen produced by the prostate also penetrates there. The function of the prostate-specific antigen in the body is unknown, and in laboratory diagnostics it is used to detect diseases of the prostate gland. Some of its fractions have antigenic properties, which makes it possible to identify them using immunochemical laboratory methods. The combination of these properties and determined the name for this substance as “prostate-specific antigen”.

Serum PSA exists in several forms. Two of them are available for determination by immunochemical methods:

1) bound prostate-specific antigen – is in a chemical bond with another compound that blocks its enzymatic function (alpha-1-antichymotrypsin),

2) free prostate-specific antigen – is in free ( unbound) state.

In sum, they reflect the level of the total prostate-specific antigen.

Small fluctuations in total PSA are closely associated with both changes in the functioning of the prostate gland, which are not pathological, and with various diseases of the prostate. For example, PSA levels are influenced by individual differences in prostate mass: a larger prostate produces, correspondingly, more PSA. In addition, the age of patients matters: the amount of PSA gradually increases throughout life. Mechanical effects on the prostate gland, such as massage or cycling, can also cause an increase in this indicator. The same effect has ejaculation.

Total PSA moderately increases with hypertrophy (adenoma) of the prostate, acute and chronic inflammatory diseases of the prostate gland (prostatitis), urinary tract infections, but the main diagnostic value of this analysis is the timely detection of prostate cancer.

Prostate cancer is one of the most common cancers in men. This disease is especially common in men over 50 years of age. In Russia, in almost 70% of patients, it is detected only at the 3-4th stage. Meanwhile, with the timely detection of prostate cancer, the effectiveness of its treatment is very high. But, unfortunately, in the early stages, this disease is asymptomatic. In this regard, during the initial visit to an oncologist, 70% of patients already have tumor spread to surrounding tissues or distant organs. That’s why it’s so important for men to get their PSA checked periodically. The classic methods for detecting prostate cancer – palpation of the prostate gland through the rectal wall in combination with ultrasound – have limited sensitivity and often do not allow timely detection of the tumor, while the PSA test makes it possible to diagnose even early, asymptomatic forms of the disease.

An increase in PSA levels at the beginning of the disease occurs as a result of dysfunction of prostate cells and increased permeability of blood vessels, which stimulates the release of specific substances from prostate cells into the extracellular environment. Tumor cells themselves synthesize prostate-specific antigen in smaller quantities than normal tissues. Thus, this test is highly specific for prostate tissue, but not for prostate tumors. However, with an increase in the total mass of tumor cells, their share in the production of prostate-specific antigen also increases, exerting an increasing influence on the results of laboratory analysis.

The higher the PSA level in the blood, the more certain it is that there is a malignant process in the prostate gland. However, if the total PSA is slightly elevated, the reliability of the diagnosis is doubtful, since the same result can be obtained with other diseases of the prostate, such as benign hypertrophy or prostatitis.

The sensitivity of the PSA indicator increases significantly when simultaneously analyzing the total and free fraction of this substance in the blood and determining the ratio of the results obtained. The proportion of free PSA in the blood serum in prostate cancer is significantly lower compared to its level in any benign process. Due to this, a more accurate distinction between benign and malignant diseases of the prostate is possible with a minimal increase in total PSA.

Early detection of prostate cancer is also carried out through an annual preventive examination. An excessive increase in PSA levels over the year indicates an increased risk of developing the disease.

The total PSA test is also used in the treatment of prostate cancer. This indicator is used to judge the success of therapy: a significant decrease in PSA levels indicates a positive result of therapeutic measures. This analysis is very important for the timely detection of recurrence of the disease after its surgical treatment.

What is research used for?

• For the early diagnosis of adenoma and inflammatory diseases of the prostate.
• For the diagnosis of ischemia or infarction of the prostate.
• For early diagnosis of prostate cancer.
• For the differential diagnosis of prostate cancer and its benign diseases, as well as infectious and inflammatory processes of the urinary tract.
• To evaluate the effectiveness of drug therapy for prostate cancer.
• To monitor the results of surgical treatment of prostate cancer.
• For the timely diagnosis of recurrence of prostate cancer after surgical treatment.
• As part of a preventive screening for the early diagnosis of benign diseases and prostate cancer.

When is the test ordered?

• For prostate symptoms.

• During examination to confirm or rule out prostate cancer.
• In monitoring the effectiveness of drug therapy for prostate cancer.
• When monitoring the patient’s condition after surgery to remove prostate cancer (for the purpose of early detection of a possible recurrence of the disease).
• For preventive examination of the prostate gland.

What do the results mean?

Reference values: 0 – 4 ng/ml.

The amount of total PSA may moderately increase under some conditions not associated with prostate disease, as well as in a number of pathological conditions. The degree of increase in its level is directly proportional to the severity of prostate disease. A low total PSA indicates a low risk of prostate disease or treatment success.

Reasons for increasing total PSA:

• relative increase in prostate mass,
• prostate massage / cycling / ejaculation less than 24 hours before the study,
• infection / inflammation of the urinary tract,
• prostate adenoma,
• prostatitis,
• ischemia / infarction of the prostate,
• prostate cancer.

Reasons for low total PSA:

• low risk of developing prostate disease,
• successful treatment of prostate disease.

Important notes

Also recommended

• Cancer embryonic antigen (CEA)

Who orders the examination?

General practitioner, internist, urologist, oncologist, surgeon.

Literature

1. Andriole GL, Crawford ED, Grubb RL et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009;360:1310 – 9.
2. Schroder FH, Hugosson J, Roobol MJ ​​et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360:1320-8.
3. Osterling JE, Jacobsen SJ, Chute CG et al. Serum prostate-specific antigen in a community-based population of healthy men: establishment of age-specific reference ranges. JAMA 1993;270:860-4.
4. Carter HB, Pearson JD, Metter EJ et al. Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease. JAMA 1992;267:2215-20.
5. Beduschi MC, Osterling JE. Percent free prostate specific antigen: the next frontier in prostate-specific antigen testing. Urology 1998;51(Appendix 5A):98 – 109.
6. Modi P, Helfand BT, McVary KT. Modifications and surgical interventions for benign prostatic hyperplasia are potential confounders of prostate-specific antigen. Curr Urol Rep 2010;11:224 – 7.
7. Gleason DF. Histologic grading and staging of prostatic carcinoma. In: Urologic Pathology: The Prostate. Philadelphia, Lea and Febiger 1977, p. 171 – 8.
8. Oesterling JE. Using PSA to eliminate unnecessary diagnostic tests: significant worldwide economic implications. Urology 1995;46(Appendix 3A):26 – 33.
9. Mitchell DM, Swindell R, Elliott T, Wylie JP, Taylor CM, Logue JP. Analysis of prostate-specific bounceafter I(125) permanent seed implant for localized prostate cancer. Radiother Oncol 2008;88:102–7.

Should I take a biopsy if my PSA is elevated?

The PSA test is considered the gold standard for diagnosing prostate health. Often, when PSA results are higher than normal, the patient is diagnosed with suspected prostate cancer and sent for a biopsy. However, it is not a fact that a high PSA level is an oncology.

Increased PSA – what to do?

A PSA test, or prostate-specific antigen, makes it possible to suspect the presence of prostate cancer. It must be taken annually by every man after 45 years. In other cases, the analysis is prescribed according to indications: if the results of ultrasound, MRI or CT, digital rectal examination raise doubts about the presence of a tumor.

There is a belief that if PSA is below 4 ng / ml – this is the norm, in fact it is not. It has been proven that PSA levels vary with age. For men under forty, the lower threshold is 2.5 ng / ml, and for the elderly – 4. 5 ng / ml. With age, the prostate enlarges, this is a normal process, and, as a result, the production of PSA increases.

If you have been scheduled for a biopsy, but you want to make sure that the order is correct, you can get a second opinion from the experts at the EMC Urology Clinic.

PHI – diagnosis of prostate cancer without biopsy

When a tumor is suspected, but the total PSA is in the range of 2-10 ng/ml, doctors usually opt for expectant management and regular monitoring, or prescribe a biopsy. The best way to clarify the situation in this case is an additional study – a PHI blood test. If the PHI is low, then the doctor may refuse to take a biopsy and continue monitoring. Studies show that up to 75% of biopsies are performed in vain, that is, they could be replaced by a PHI blood test.

Magnetic resonance imaging (MRI)

MRI of the prostate may also help avoid a biopsy. MRI of the prostate, unlike a biopsy, is a non-invasive diagnostic method that does not injure the body and does not expose it to radiation. MRI allows accurate visualization of pathological foci even at the earliest stages of the development of the disease and confirms or refutes the need for a biopsy.

Fusion biopsy – the most accurate way to diagnose cancer

Prostate biopsy is a method of examining prostate tissue for cancer cells. Using a special needle, rectal or urethral punctures are made in the prostate in order to take suspicious tissue for examination.

EMC is one of the few clinics in Russia that does not perform a classic biopsy, but a fusion biopsy. With a classic biopsy, the doctor acts, one might say, blindly, even if the procedure is performed under ultrasound guidance. Fusion biopsy is a procedure carried out under the combined control of ultrasound and MRI. This technology allows you to take the material exactly from the area that is in doubt.