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ORIGINAL ARTICLE
UTILITY OF PROSTATE SPECIFIC ANTIGEN VALUES IN DIAGNOSIS AND
MANAGEMENT OF PROSTATE CANCER
A.M. Acharya
1.
Lecturer. Department of Surgery, Konaseema Institute of Medical Sciences & Research, Amalapuram.
CORRESPONDING AUTHOR:
Dr. Mrs. A. M. Acharya,
Lecturer, Dept of Surgery,
Konaseema Institute of medical sciences and research foundation,
NH-216, Chaitanya Nagar, Amalapuram - 533 201,
East Godavari District, Andhra Pradesh.
E-mail: [email protected]
ABSTRACT: Prostate specific antigen (PSA) is a popular & time tested, easy and cheap
investigation used in the diagnosis of prostate cancer. However it very important to know its
limitations, reasons for the limitations like its relation to age of the individual, associated benign
enlargement, any procedure or instrumentation done before the estimation etc. Blind cut off
values without consideration given to these facts may lead to unnecessary biopsies and
apprehension. Modified procedures like PSA density, rising values, ratio of its two molecular
forms pro PSA/ Benign PSA (BPSA) give more information, however these are costlier and more
sophisticated investigations that are not available at peripheral centers, in India.
INTRODUCTION: Prostate specific antigen (PSA) is a popular and time tested investigation
used in diagnosis and management of prostate cancer. However at times this may lead to
unnecessary biopsies and apprehension. It is necessary to know the limitations of this test, facts
and reasons behind these limitations, the attempts being made world over at improvements in
interpretation of the results.
TEXT: - Prostate specific antigen is synthesized in the ductal and acinar epithelium of prostate.
It is found in normal, hyper plastic and malignant prostatic tissue. It is a serine protease of
kallikrein family. Majority of PSA is added to the seminal fluid through prostatic secretions.
Here it functions to release the spermatozoa trapped in the seminal clot, by cleavage of high
molecular weight protein responsible for coagulation of semen1.
A small amount of PSA reaches serum by diffusion from luminal cells. In serum most of
the PSA is in the form of a complex formed between PSA and α1 anti chymotrypsin (PSA-ACT)
and a small amount is in free form. In prostatic cancer the PSA-ACT levels are raised more than
the free component2.
PSA levels are directly proportional to the probability of cancer detection on a prostatic
biopsy. PSA levels < 4ng/ml are considered to be normal. However even with a level of < 2ng/ml
of PSA a proportionate risk of cancer is indicated3.
Journal of Evolution of Medical and Dental Sciences/ Volume 2/ Issue 16/ April 22, 2013
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ORIGINAL ARTICLE
PSA Risk of Cancer
<2ng/ml <2%
2.5-4ng/ml 18%
4-10ng/ml 25%
>10ng/ml 67%
Raised PSA levels are not diagnostic of prostate cancer because benign prostate tissue
also produces PSA. Hence Benign Prostatic Hyperplasia (BPH), Prostatitis, Prostatic infarcts,
acute urinary retention, cystoscopic examination, instrumentation of prostate & even
ejaculation cause a rise in serum PSA levels. Routine Digital Rectal Examination (DRE) does not
appear to elevate PSA levels but vigorous prostatic massage (1.5-2 times) 4& needle biopsy of
prostate does. So in situations of such a kind one should wait for 4-6 weeks before estimating
serum PSA. Finasteride is the drug used in treatment of BPH and also for hair loss. Use of this
drug lowers the PSA level by about 50%3.
Clinical usefulness of PSA & Prostatic Acid Phosphatase (PAP) has been compared by
researchers4. Thomas Stamey et al observed that PSA levels increase with advancing clinical
stage & are proportional to the estimated volume of the tumor, while PAP is not a sensitive
marker & does not correlate with the tumor volume. However they also observed that PSA was
increased in most of (86%) BPH patients too, while PAP was raised in only few of them (14%) 4
PSA is the most useful immuno cytological marker. Its sensitivity & specificity is 100% in
identifying tissue of prostatic origin. PSA is more precise & meaningful marker in all situations.
After radical prostatectomy PSA drops to undetectable level while PAP remains detectable.
Irrespective of treatment modality PSA predicts accurately tumor recurrence months before its
detection by any other method1.
In spite of these useful properties, PSA is not sufficiently reliable in determining either
clinical or pathological stage of prostatic cancer. So as to increase the clinical utility, study of
PSA levels can be combined with DRE, Trans Rectal Ultra Sound (TRUS) & Gleason’s score.5, 6
individually each one of them is a good predictor of pathologic stage, although PSA is far better
predictor compared to DRE7. However a combination of these three predictors gives best
results especially in an early cancer detection program1. Certain issues regarding utility of PSA
values in detection & management of prostatic cancer have been addressed by various workers
over time & again. One of these issues is that the values are influenced by associated BEP in
patients harboring prostatic cancer; secondly the tumor differentiation also influences the PSA
values because the PSA production by tumor cells decreases with increasing grade of tumour8.
Another issue of practical importance is that because majority of patients having prostate
cancer are older than 65 years of age & this cancer progresses slowly over years, how far early
detection & early treatment influence the overall mortality & morbidity due to prostatic cancer
is debatable8.
To overcome these difficulties & to improve the utility of PSA study certain variations of
PSA have been developed.
PSA Density3– It is the PSA produced per gram of prostate tissue. PSA density can be
useful in distinguishing BPH from prostate cancer9. It is calculated by dividing total PSA by
estimated gland volume by TRUS or Magnetic Resonance Imaging (MRI) or by actual dimensions
of surgical specimen (length x width x depth x 0.05 = volume).3,9 A value of 0.15 ng is
considered upper normal. However the estimated gland volume by TRUS does not correlate well
with actual volume & hence this may not be a useful parameter3
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ORIGINAL ARTICLE
With advancing age the prostate enlarges. By studying a large group of men of varying
ages who are not having prostate cancer the upper reference ranges are supposed to be –
Age PSA
40 – 49 yrs. 2.5 ng/ml
50 -59 yrs. 3.5 ng/ml
60 – 69 yrs. 4.5 ng/ml
70 -79 yrs. 6.5 ng/ml
These age related cut off values will help in early detection of prostate cancer occurring
in younger men with lower PSA values and it will also reduce the number of unnecessary
biopsies in older men with higher PSA values. For example if a 45 year old man has Serum PSA
of 3.5 ng/ml he should be biopsied in spite of PSA value < 4 ng/ml, while a 75 year old man with
serum PSA of 6 ng/ml need not undergo biopsy in spite of PSA > 4ng/ml.
PSA Velocity3– It is based on a study where PSA levels were studied in men every 2 years10.
Increased rate of rise in PSA correlated with eventual detection of prostate cancer. PSA velocity
of 0.75 ng/ml per year was observed in 72% of men who eventually were detected to have
prostate cancer, while only 5% of men who did not have prostate cancer crossed this value. To
make this test more valid at least 3 PSA measurements should be done over a period of 1.5-2
years. A rise in PSA velocity should prompt a work up for detection of prostate cancer even if
the values are < 4 ng/ml.
Molecular forms of PSA3 – In circulation most of the PSA is bound to serine protease
inhibitors. Three most recognizable of them are α1 anti chymotrypsin (ACT), α1 macroglobulin
& α1 protein inhibitor. PSA-ACT is the most immune reactive form & is useful clinically in
detecting prostate cancer. A small fraction of PSA is free PSA in serum. Men with PSA values of
2.5-10 ng/ml with ≥ 25% free PSA are less likely (5% risk) to have prostate cancer. Free PSA
value of < 10% is worrisome for cancer.
Men with normal DRE and PSA values between 4-10 ng/ml can be benefitted by
estimation of free PSA & unnecessary biopsies can be avoided, which may count to about 2030% of total number of biopsies.
Recently additional iso forms of free PSA have been identified. Precursor form of PSAPro PSA constitutes majority of free PSA in men with prostate cancer. Benign form of PSA
(BPSA) is the cleaved form of PSA from benign prostatic tissue. The ratio of Pro PSA / BPSA is
considered as a means of improving the accuracy of diagnosing cancer in men in high risk
category with low (< 15%) value of free PSA11.
Role of PSA in follow up – After radical prostatectomy PSA level should fall to
undetectable levels. Values >0.2 ng/ml indicate persistent or recurrent disease. Ultra sensitive
assay methods can detect very low levels of PSA and are being used by some12. After
radiotherapy the PSA values decrease but not to the same extent as after radical prostatectomy.
Hence subsequent rising PSA values (3 values) are considered to be a sign of treatment failure.3
CONCLUSION: So as to make PSA estimation more informative, it should always be interpreted
in light of age of individual, results of DRE & TRUS and estimated volume of prostatic tissue.
Rising values are useful in follow up studies. Molecular forms of PSA can be tested to give more
information though this is not done in peripheral laboratories.
Journal of Evolution of Medical and Dental Sciences/ Volume 2/ Issue 16/ April 22, 2013
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ORIGINAL ARTICLE
REFERENCES:
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antigen. http://dx.doi.org/10.1006/scbi. 1998.0086,
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Philadelphia: Lipincott Williams &Wilkins, 2008: 1-5.
4. Thomas A Stamey, Norman Yang, Alan R Hay, John E McNeal, Fuad S Freiha & Elsie
Redwine. Prostate specific antigen as a serum marker for Adenocarcinoma of the
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Biopsy interpretation of the prostate.4th ed. Philadelphia: Lipincott Williams &Wilkins,
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11. Kahn MA, SOKOLL LJ, Chan DW et al Clinical utility of proPSA and ‘benign’ PSA when
percent free PSA is less than 15%. Urology. 2004; 64:1160-1164.
12. Shen S, Lepor H, Yaffee R, et al.Ultrasensitive serum prostate specific antigen nadir
accurately predicts the risk of early relapse after radical prostatectomy. J Urol.2005;
173:777-780.
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