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.