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Prostate-specific antigen (PSA)

Prostate-Specific Antigen (PSA): Overview, Clinical Use, and Limitations

Prostate-specific antigen (PSA) is a serine protease produced by prostate epithelial cells, primarily used as a blood biomarker to detect prostate cancer (PCa) and monitor its progression. While widely employed, PSA testing has limitations due to its low specificity, as elevated levels can also occur in benign conditions.

Biology of PSA

1. Production:
   • Secreted by prostate cells into seminal fluid, where it liquefies semen to facilitate sperm mobility14.
   • Enters the bloodstream in small amounts, rising in prostate cancer, benign prostatic hyperplasia (BPH), or prostatitis23.
2. Forms:
   • Total PSA: Bound to proteins (e.g., alpha1-antichymotrypsin) or free in the blood15.
   • Free PSA: Unbound PSA; higher ratios of free-to-total PSA may reduce false positives for PCa17.
3. Role in PCa:
   • PCa cells produce less PSA per cell than healthy cells, but elevated total PSA levels occur due to increased cell numbers47.

Clinical Use of PSA Testing

1. Screening:
   • Not universally recommended due to risks of overdiagnosis (detecting slow-growing tumors) and overtreatment26.
   • Guidelines: Discuss risks/benefits with a doctor, especially for men aged 55–69 or those with risk factors (e.g., family history)26.
2. Diagnosis:
   • Elevated PSA: Triggers further testing (e.g., biopsy, MRI) to confirm PCa38.
   • Limitations:
     • False positives: BPH, prostatitis, or medications (e.g., finasteride) can raise PSA35.
     • False negatives: Some aggressive PCa may have normal PSA7.
3. Monitoring:
   • Post-treatment: Tracks recurrence in PCa patients8.

PSA Test Results

PSA Level	Interpretation
<4 ng/mL	Low risk of PCa; may still require biopsy if symptoms persist58.
4–10 ng/mL	Moderate risk; free PSA ratio or biopsy may clarify17.
>10 ng/mL	High risk; biopsy strongly recommended58.

Limitations and Controversies

1. Low Specificity:
   • False alarms: BPH and prostatitis account for ~75% of elevated PSA cases27.
2. Overdiagnosis:
   • Detects indolent tumors that may never cause harm, leading to unnecessary treatments26.
3. Emerging Biomarkers:
   • ProPSA isoforms (e.g., [-2]proPSA) and PCA3 are under study to improve specificity17.

Forensic Use

PSA is used to detect semen in sexual assault cases, as it is abundant in seminal fluid and persists even in vasectomized individuals4.

Conclusion

PSA testing remains a key tool in prostate cancer management but requires cautious interpretation. While it aids early detection, its limitations highlight the need for shared decision-making and advanced biomarkers to reduce unnecessary interventions.

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References

1. PubMed: Biology of PSA
2. NCI: PSA Test
3. WebMD: PSA Test
4. Wikipedia: PSA
5. MedlinePlus: PSA Test
6. Mayo Clinic: PSA Test
7. StatPearls: PSA
8. Cleveland Clinic: PSA Test