Prostate-specific antigen is a protein produced by the prostate gland. The prostate gland is a male accessory gland found at the base of the urinary bladder. Generally, a random blood (serum) sample is taken for testing; a PSA level up to 4 ng/mL is considered normal. PSA levels increase with age; hence, a higher cut-off (5 ng/mL) would apply for elderly men above 70 years, and a lower cut-off (2.5 ng/mL) would apply for younger men below 55 years and for patients on drugs to reduce the size of the prostate due to BPH (dutasteride and finasteride). The clinical history of the patient is vital in identifying temporary causes of an abnormal rise in PSA. Causes could include an infection, inflammation of the prostate, prostatic biopsy, urinary catheterisation, urological procedures, vigorous exercise (cycling), and recent sexual activity (ejaculation).
If the PSA is above 4 ng/mL, a thorough clinical evaluation is essential, with particular emphasis on a digital rectal examination (DRE) and a detailed patient history. For clinically unremarkable men, a repeat PSA test and urine routine examination should be performed, with urine culture if necessary. Imaging of the prostate–either by ultrasound or MRI–should be performed before considering a prostatic biopsy.
Cancer Prostate and PSA
Screening Tool for Prostate Cancer
Generally, men above 50 years undergo PSA screening. If the PSA is less than 2.5 ng/mL, second yearly screening is advised; if more than 2.5 ng/mL, yearly screening is advised. They should be informed about the benefits, risks and uncertainties of the prostate cancer screening. However, those with a strong family history of prostate cancer (father or brother), Black men and men with inherited variants (BRACA2 should this be BRCA2? and to a lesser extent BRCA1) are advised regular yearly screening of PSA.
The potential benefit of screening lies in the early detection of cancer, which can allow for timely intervention and a complete cure. However, in certain patients, overdiagnosis and over-treatment may occur, leading to unnecessary complications and a negative impact on quality of life. Asymptomatic advanced cancer is also diagnosed during screening in a small population. Additionally, screening may miss PSA independent prostate cancer where PSA may be normal or low.
Diagnosis of Prostate Cancer
Most often, a diagnosis of prostate cancer based on a single high PSA level with normal DRE can be misleading. Therefore, repeating the test after 4 to 6 weeks and excluding other temporary causes and benign enlargement of prostate (BPH) is mandatory before proceeding with an MRI and prostatic biopsy.
In patients with equivocal findings, parameters such as free PSA, PSA velocity and PSA density may have a role in predicting prostate cancer. However, their accuracy is limited.
There are newer blood and urine tests like PCA3 (prostate cancer gene 3), ExoDx and 4Kscore test, that are emerging to predict cancer risk and behaviour.
Prostate Cancer Follow-Up
PSA plays an important role in the follow-up of patients with prostate cancer who underwent curative or palliative treatment.
Regular monitoring of PSA (typically every 6-12 months after surgery or radiation therapy) helps in early detection of disease recurrence. If a significant rise is observed, more frequent testing, such as monthly or bimonthly measurements, may be required to establish a true trend.
In patients with advanced prostate cancer, PSA helps in predicting response to treatment as well as the development of treatment resistance. Although PSA independent prostate cancer is rare, it poses significant challenges and is difficult both to treat and monitor effectively.
Conclusion
PSA testing has significantly improved early detection of prostate cancer and contributed to better treatment outcomes. However, it also has a tendency to overdiagnose and over-treat less aggressive cancer, which can result in unnecessary complications.
Prostate cancer behaviour can be indolent to aggressive. So, the best treatment relies on good clinical judgement that integrates PSA levels, patient age, biopsy grade and disease stage.
Dr M Jeevagan
Senior Consultant Urologist,
Kauvery Hospital, Chennai
