Prostate specific antigen

Nature: PSA is a serine protease (kallikrein-3) produced by prostatic epithelial cells; its physiological role is to liquefy semen. It is organ-specific but not cancer-specific.

Reference value: the widely used cut-off is 4.0 ng/mL. However, about 25% of men with prostate cancer have a PSA of 4.0 ng/mL or less, and PSA specificity is lower in men with obstructive symptoms than in asymptomatic men.

Causes of a raised PSA other than cancer: benign prostatic hyperplasia, prostatitis and male urinary tract infection, acute retention, catheterisation and instrumentation, prostate biopsy, digital rectal examination and prostatic massage, ejaculation, and vigorous cycling.

Causes of a falsely low PSA: 5-α-reductase inhibitors halve the value — double the measured PSA for interpretation; also obesity (haemodilution) and some herbal preparations.

Refinements to improve specificity: PSA density (PSA ÷ prostate volume), age-specific reference ranges, PSA velocity, free-to-total PSA ratio, and PSA doubling time (a doubling time <10 months indicates aggressive non-metastatic castration-resistant disease).

Role in BPH: PSA measurement remains recommended in the evaluation of LUTS by AUA guidance, and serum PSA is a stronger predictor of future prostate growth than age or baseline prostate volume, making it a useful predictor of acute urinary retention and of who will benefit from a 5-α-reductase inhibitor.

Role in cancer: used for detection (with DRE and imaging), risk stratification, monitoring after radical treatment (biochemical recurrence), and monitoring response in advanced disease.

Screening in older adults — the key geriatric point: guidance applies to men with a life expectancy of more than 10 years. Screening should follow shared decision-making, weighing over-diagnosis, over-treatment and biopsy complications against a modest mortality benefit; it is generally not appropriate in frail elders or those with limited life expectancy.

Do not measure PSA during a male urinary tract infection — the value is unreliable and takes about six months to return to baseline after infection.

Indian context: report PSA in ng/mL. There is no organised national prostate cancer screening programme in India; opportunistic testing without counselling risks over-diagnosis, and prostate cancer often presents late with bone metastases and obstructive uropathy in Indian practice.

AUA/SUO Early Detection of Prostate Cancer Guideline (2023, updated 2026) anchors screening in shared decision-making and integrates secondary biomarkers and prostate MRI before biopsy to reduce unnecessary biopsies and detection of indolent disease.

The Stockholm3 multi-analyte risk test, in the STHLM3 and STHLM3-MRI randomised screening studies, has shown greater clinical net benefit than PSA alone — fewer false negatives, fewer biopsies and less over-diagnosis, with 9-year outcome data (2025) confirming improved detection of aggressive cancers.

MRI-first pathways with targeted biopsy are now standard where available, substantially reducing detection of clinically insignificant (Grade Group 1) cancer while maintaining detection of significant disease.

PSA is kallikrein-3 — organ-specific, not cancer-specific.

Cut-off 4.0 ng/mL, but 25% of prostate cancers have a PSA at or below this.

5-α-reductase inhibitors halve PSA — double the value.

Do not check PSA during a male UTI; allow six months for recovery.

PSA predicts prostate growth and acute retention better than age or volume.

Screening only where life expectancy exceeds 10 years, after shared decision-making.

Modern pathway: PSA → biomarker/MRI → targeted biopsy.