Introduction
Prostate-specific antigen, commonly known as PSA, is currently the main biomarker used for the early detection of prostate cancer. However, its use requires careful interpretation, because elevated values do not necessarily indicate malignant disease and may occur in several benign conditions. PSA testing should therefore result from shared decision-making between the clinician and the patient, taking into account the potential benefits of early diagnosis as well as the risks associated with overdiagnosis and overtreatment.
Selecting candidates for screening
The algorithm begins by identifying appropriate candidates for opportunistic screening. In general, assessment is considered between 50 and 69 years of age, although it may be discussed earlier in men with relevant risk factors, such as a family history of prostate cancer in a first-degree relative, African ancestry or genetic mutations associated with increased risk, particularly BRCA2. Between 70 and 75 years of age, the decision should be individualised according to life expectancy, comorbidities and the patient’s preferences.
Excluding transient causes of PSA elevation
Before requesting PSA testing, it is important to exclude conditions that may cause a transient increase in the marker. These include urinary tract infection, prostatitis, urinary retention, recent ejaculation, strenuous physical exercise, particularly cycling, and recent urological procedures or manipulation. The presence of these factors may produce falsely elevated results and lead to unnecessary investigation.
Initial interpretation of PSA
After testing, the algorithm proposes a risk-stratified approach. PSA values below 1 ng/mL are generally associated with a very low risk of clinically significant prostate cancer, allowing longer surveillance intervals, usually between four and eight years. When PSA is between 1 and 3 ng/mL, reassessment after two to four years is recommended.
PSA between 3 and 10 ng/mL
A different approach is required when PSA is between 3 and 10 ng/mL. In these cases, interpreting a single result may be misleading. The recommended strategy is therefore to repeat PSA after six to twelve weeks, having first ensured that no transient factors are responsible for the elevation. This approach helps avoid unnecessary referrals and additional investigations in men whose PSA subsequently normalises.
Persistent PSA elevation
If PSA remains at or above 3 ng/mL after repeat testing, the next step is a digital rectal examination. Despite the development of newer diagnostic methods, digital rectal examination continues to play an important role in the clinical assessment of the prostate. The presence of induration, marked asymmetry or suspicious nodules significantly increases the probability of clinically relevant malignancy and warrants referral to Urology.
Use of the free-to-total PSA ratio
When digital rectal examination is normal, the algorithm proposes measurement of the free-to-total PSA ratio. This parameter may help distinguish lower-risk situations from cases with a higher probability of prostate cancer. In general, a ratio below 25% is associated with a higher risk of clinically significant disease and should prompt specialist assessment. In contrast, values at or above 25% suggest a lower probability of clinically relevant malignancy and often allow a strategy of periodic surveillance.
Criteria for priority referral
One situation requires particular attention. PSA values at or above 10 ng/mL warrant priority referral to Urology, regardless of the remaining findings, because of the higher probability of clinically significant disease and the need for prompt further investigation.
Additional considerations
It is important to remember that PSA is only one component of the clinical assessment. Age, family history, African ancestry, the presence of hereditary mutations such as BRCA2 and physical examination findings should always be integrated into decision-making. Following referral, many patients currently also undergo multiparametric magnetic resonance imaging of the prostate, which plays an increasingly important role in risk stratification and in selecting candidates for biopsy.
Conclusion
In summary, this algorithm aims to promote the rational use of PSA, reducing unnecessary investigations without compromising the early detection of clinically significant prostate cancer. Combining shared decision-making, repeat testing of intermediate values, structured clinical assessment and appropriate referral enables a balanced approach aligned with the most recent international recommendations.
