Dr. Jad Alsmadi, MD., Assistant Professor, Faculty of Medicine, The Hashemite University

PSA
Dr. Jad AlSmadi, MD.,

Assistant Professor,
faculty of medicine,
The Hashemite University
PSA
• PSA is a glycoprotein produced primarily by the epithelial
cells that line the acini and ducts of the prostate gland.
• PSA acts physiologically like a serine protease and an
arginine esterase with chymotrypsin-like and trypsin-like
activity.
• One of the structural proteins of the seminal fluid,
semenogelin, causes the ejaculate to clot. One possible
biologic role of PSA is to lyse the clot in the ejaculate
• PSA is concentrated in prostatic tissue, and serum PSA
levels are normally very low.
PSA
• Disruption of the normal prostatic architecture, such as by

prostatic disease, inflammation, or trauma, allows greater
amounts of PSA to enter the general circulation.
• Elevated serum PSA level has become an important marker
of many prostate diseases – including benign prostatic
hyperplasia (BPH), prostatitis, and prostate cancer.
• Prostatic intraepithelial neoplasia (PIN) does not appear to
raise serum PSA levels.
PSA
• The ectopic expression of PSA has been reported in smaller
concentrations in the tissue of malignant breast tumors,
normal breast tissue, breast milk, female serum, and adrenal
and renal carcinomas;
• however, for practical and clinical purposes, PSA is an
androgen-dependent and prostate organ-specific (but not
a cancer-specific) marker.
• A limitation of PSA as a tumor marker is demonstrated in
the substantial overlap in values between benign and
malignant prostate disease
PSA
• The concentrations found in seminal plasma range from 0.5
to 5.0 mg/mL, whereas normal serum concentrations in men
aged 50 to 80 years without prostatic disease range from 1.0
to 4.0 ng/mL.
• A small proportion of active PSA diffuses into the
circulation, where it is rapidly bound or complexed by
covalent attachment to protease inhibitors (most
commonly, α1-antichymotrypsin (ACT))
• Inactive PSA can also enter the bloodstream, where it
circulates in an unbound state as free PSA (fPSA).
PSA
• Inactive PSA can also enter the bloodstream, where it

circulates in an unbound state as free PSA (fPSA).
• PSA expression is strongly androgen dependent: = bimodal
peaks between 0-6 months and after 10 years of age
• In the absence of prostate cancer, serum PSA levels vary
with age, race, and prostate volume
PSA
• In prostate cancer, the loss of gland architecture and basal

cells results in a decrease in the luminal processing of
proPSA to active PSA (and thus an increase in proPSA) thus
decreasing the amount of fPSA.
• Clinicl application of PSA derivatives such as PSA density,
PSA velocity, age-adjusted values, and, more recently,
molecular derivatives may be used to improve clinical
decisions.
PSA Velocity
• In normal men, the rate of change in PSA is 0.04 ng/mL per

year, compared with 0.07 to 0.27 ng/mL per year in men with
BPH who are between the ages of 60 and 85 years.
• PSA velocity is of minimal use for prostate cancer screening.
• PSA velocity should not be used as a trigger for biopsy.
• The main benefit in Active Surveillance.
PSA Density
• Total PSA divided by prostate volume.

• Proposed cutoffs for biopsy in the early detection setting
have ranged from 0.08-0.15 ng/mL2.
• PSAD cutoff of 0.150 is the classical one.
• PSAD at a cutoff of ≤0.08 averts 13% of biopsies, while
missing 2.7% of all cancers and only 0.47% of potentially
clinically significant cancers.
Free PSA
• PSA produced from malignant cells appears to more

frequently escape proteolytic processing, resulting in a
greater fraction of serum PSA complexed to ACT and a lower
percentage of total PSA that is free compared with men
without prostate cancer.
• fPSA testing: improve the accuracy of PSA as a prostate
cancer screening biomarker, and the FDA has approved its
use in men with a serum total PSA level of 4-10 ng/mL and a
negative DRE.
Free/Total PSA Ratio
• Within the tPSA range of 4 to 10 ng/mL;

• Proposed cut points generally range from 15% to 25%
• 20% to 65% of unnecessary biopsies may be avoided,
while maintaining sensitivity rates of 70% to 95%
• Positive predictive rate of total PSA greater than 10
ng/mL has been demonstrated to be as high as 80%
Causes of elevated PSA
1. Prostate disease (BPH, prostatitis, prost ca)
2. Prostatic inflammation (acute and chronic)
3. Urinary retention
4. prostate manipulation (prostate massage, Cystoscopy)
5. Ejaculation: only >50 y.o (returens to NL within 24 hr
6. Prostate trauma: Biopsy, bicycling
Causes of low PSA
1. Low testosterone levels
2. Anti-androgen therapy (ADT)
3. Finasteride/ dutasteride treatment
4. Prostatectomy
5. Infiltrative diseases replacing prostatic tissues
6. Malignant diseases replacing prostatic tissues
Summary
• TPSA <4 is generally normal.

• TPSA between 4-10 use: f/T ratio, density, or
velocity.
• TPSA >10 is generally considered abnormal.
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Dr. Jad Alsmadi, MD., Assistant Professor, Faculty of Medicine, The Hashemite University

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Dr. Jad Alsmadi, MD., Assistant Professor, Faculty of Medicine, The Hashemite University

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PSA

Dr. Jad AlSmadi, MD.,

• Disruption of the normal prostatic architecture, such as by

• Inactive PSA can also enter the bloodstream, where it

• In prostate cancer, the loss of gland architecture and basal

• In normal men, the rate of change in PSA is 0.04 ng/mL per

• Total PSA divided by prostate volume.

• PSA produced from malignant cells appears to more

• Within the tPSA range of 4 to 10 ng/mL;

• TPSA <4 is generally normal.

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