Serum prostate-specific antigen (PSA) concentrations in normal men are low, and PSA concentrations in semen are about 1 million times higher than serum PSA concentrations.
This is because the prostate epithelium is underlain by a dense basement membrane that acts as a “high wall” separating the epithelium from the blood. So almost all of the PSA can only enter the semen through the ducts, but not the bloodstream.
When you have prostate disease, the basement membrane is damaged to varying degrees, especially in prostate cancer, where the abnormal growth of cancer cells can severely damage the basement membrane and allow PSA to enter the bloodstream through this “abnormal pathway”. The PSA concentration in the lumen of the prostate is much higher than in the blood, resulting in a significant increase in serum PSA levels.