Clinical meaning
Prostate-specific antigen (PSA) is a serine protease produced by prostatic epithelial cells that liquefies semen. PSA is organ-specific but not cancer-specific - it is elevated in BPH, prostatitis, urinary retention, ejaculation, and prostate manipulation, in addition to prostate cancer. Prostate adenocarcinoma arises predominantly from the peripheral zone (70%) and progresses from prostatic intraepithelial neoplasia (PIN) through well-differentiated to poorly differentiated carcinoma. The Gleason grading system evaluates glandular architecture: Grade Group 1 (Gleason 3+3=6) is indolent, while Grade Group 5 (Gleason 9-10) is aggressive with high metastatic potential. Screening with PSA aims to detect clinically significant cancer (Grade Group >= 2) at a curable stage, but carries substantial risk of overdiagnosis and overtreatment of indolent disease. Shared decision-making is essential, weighing the potential mortality reduction (approximately 20% relative reduction per ERSPC trial) against risks of biopsy complications and treatment side effects.
Diagnosis & workup
Diagnostics & workup: - Serum PSA level (age-adjusted thresholds: > 2.5 ng/mL age 40-49, > 3.5 age 50-59, > 4.5 age 60-69) - Digital rectal exam (DRE) for nodules, asymmetry, or induration - PSA velocity (increase > 0.75 ng/mL per year raises suspicion) - Free-to-total PSA ratio (< 10% favours cancer; > 25% favours BPH) - Prostate Health Index (PHI) or 4Kscore for risk stratification before biopsy - MRI prostate (PI-RADS scoring) before biopsy to identify targets