PSA by Dr. Jeffrey Wong

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Glossary

PSA by Jeffrey E. Wong, MD, FACS

Historical Perspective

PSA is an endogenous serine protease and a member of the human kallikrein gene family identified in 1970. It is a 33kd protein produced and secreted primarily by the prostatic epithelium and epithelial lining of the periurethral gland. When secreted during ejaculation, PSA liquefies the seminal coagulum.

Factors Influencing PSA Measurement

PSA and/or PSA gene expression has been detected in the endometrium, normal and diseased breast tissue, including male and female breast tumors, breast milk, and cystic fluid, some adrenal and RCC
one of main limitations for using PSA as a tumor marker is the overlap in PSA values between men with BPH and prostate cancer
finasteride decreases total PSA in men without prostate cancer by 50% after 6 mos of treatment and free PSA not altered
PSA increased in acute prostatitis and subclinical prostatitis
also increased in urinary retention and after ejaculation
routine DRE, cysto, catheterization, and TRUS do not appear to cause clinically significant elevations in PSA levels, biopsy can elevate levels
half life is 2.2 to 3.2 days
in general, should wait approximately 4-6 wks following resolution of inciting event(biopsy, acute prostatitis)

Molecular Forms of PSA

majority of PSA is complexed irreversibly to alpha 1-antichymotrypsin, although an undetermined proportion is bound to alph 2-macroglobulin
free PSA: as the percentage decreases, the probability of having prostate cancer increases

The ProstAssure Index

variables in the index include 1) patient age, 2) serum PSA, 3) serum prostatic acid phosphatase 4) serum creatinine kinase
the values are analyzed using the "Artificial Neural Network"
values can range from <0 to >1.0
four zones: zone 1:<0.0     2%
zone 2: 0-0.5     16%
zone 3: 0.5-1     33%
zone 4: >1     90%
risk of prostate cancer increases with each higher zone
index values>0.5 should get biopsies
25-35% of men treated for prostate cancer have PSA less than 4

Age Specific PSA Reference Ranges

afford greater sensitivity for cancer detection in younger men

PSA Velocity

need 3 PSA measurements in at least 12 to 18 mos
.75 ng/ml/yr(72% sensitivity, 95% negativity) was strongly suggestive of cancer
(PSA2-PSA1/time1in yrs) + (PSA3-PSA2/time2 in yrs)

PSA Density

defined as the total serum PSA level(in ng/ml)divided by the transrectal ultrasound determined prostate volume in cc
cutoff of 0.15
has not been found to be reliable adjunctive measure to determine utility of prostate bx in men with normal DRE and intermediate PSA level
at present T1c is most common clinical stage
measuring PSA every other year in men with PSA level <2.5 and normal DRE is unlikely to miss a curable cancer, if PSA >2.5 then follow annually

Monitoring After Radical Prostatectomy

PSA levels decline rapidly to undetectable levels compared to post radiation therapy which can take 6 weeks
initial testing should begin at 3 mos
failure of PSA to become undetectable signifies local or distant disease
PSA doubling time of less than 6 mos indicated metastatic disease
PSA after XRT is unpredictable, often look at nadir PSA
PSA after androgen deprivation may take 6 mos to fall
prostate specific membrane antigen(PSMA) appears to be a marker for hormone resistant, progressive prostate cancer

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