Prostate Specific Antigen or PSA is a glycoprotein produced by prostatic epithelial cells.
It is prostate specific but not prostate cancer specific.
Levels may be elevated in men with prostate cancer as
- PSA production is increased
- Tissue barriers between the gland lumen and the capillaries are disrupted, releasing more PSA into the serum.
AGE SPECIFIC PSA VALUES
Cut off points for benign prostate disease
- 40-49 years: 0-2.5 ng/ml
- 50-59 years: 0-3.5 ng/ml
- 60-69 years: 0-4.5ng/ml
- 70-79 years: 0-6.5ng/ml
CAUSES OF LOWER PSA VALUES
Cut off values must be reduced in certain cases:
- 5-alfa reductase inhibitors
Finasteride-lowers PSA by 50% within 6 months of use.
Dutasteride-lowers PSA by 48 to 57% ; rise in PSA levels while on dutasteride is associated with higher risk of prostate cancer.
- NSAIDs and acetaminophen
Herbal remedies like Saw palmetto
INFLAMMATORY CAUSES OF INCREASED PSA
- Prostatitis (remains elevated for upto 6 to 8 weeks)
- Urinary tract infections
- Prostatic biopsy (remains elevated for upto 6 weeks—raised by about 7 ng/ml within 4 to 24 hours after the procedure)
- Transurethral Resection of the Prostate /TURP (remains elevated for upto 3 weeks –raised by about 6ng/ml)
- Urethral catheterization
- Urethral instrumentation e.g. cystoscopy
- Perineal trauma
- Prostatic infarction
- Digital rectal examination does not increase PSA
NON INFLAMMATORY & NONMALIGNANT CAUSES OF INCREASED PSA
- Increasing age. Though PSA level in an 80 year old is higher than in a 65 year old it is clinically more pertinent to do periodic checking of PSA in the latter patient.
- Urinary retention (remains elevated for upto 2 weeks)
- Vigorous exercise (remains elevated for upto 48 hours)
- Ejaculation (remains elevated for upto 48 hours- increases by upto 0.8ng/ml)
DRAWBACKS OF PSA
- PSA is produced by both malignant and benign prostatic tissue- hence not very specific.
- Even with moderately high levels (>10 mcg/L) the positive predictive value for cancer is only 65%.
- Specificity further reduces with older patients as benign causes of elevated PSA are more common.
- Two thirds of men with high PSA do not have prostate cancer.
- One fifth of men with prostate cancer have a normal PSA. Hence a hard, nodular, irregular prostate found on DRE (digital rectal examination) must be biopsied even if PSA is normal.
FREE PSA /TOTAL PSA
- Most PSA in the blood is bound to proteins. A small amount is not protein bound and is called free PSA.
- In prostate cancer the ratio of free (unbound) PSA to total PSA is decreased, risk increasing if the ratio is less than 25%. Lower the ratio, greater the probability of prostate cancer.
- Also ask for free PSA when total PSA is between 4 and 10. The risk of cancer is under 10% when the free PSA is > 25% of total but is as high as 36% if free PSA is <10%.
It refers to the rate of change of PSA values over time. It is particularly useful in men with seemingly normal values rising over a period of time. For example, an increase in PSA from 2.5ng/ml to 3.2ng/ml in a one year period would warrant further testing for cancer. A PSA velocity of more than 0.5ng/ml per year must be considered an indication for biopsy if the baseline PSA is less than 4ng/ml. If the baseline PSA is > 4ng/ml, a PSA velocity of greater than 0.75ng/ml is considered significant.