Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
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        Prostate specific antigen (PSA)
      
Autopsy series have shown a least small prostate cancers in 29% of men 30-40 years old and 64% of men 60-70 years old; the lifetime risk for men for getting prostate cancer (Pca, PCa, PC, or CaP) is 1 in 62. The screening use of the PSA test has revolutionized the ability to detect Pca early and has shifted the stage of the cancers sharply to an earlier stage. Yet, recent studies show that nearly half of the expected cancers are not detected (see table) by biopsies when the threshold for diagnostic action is between 3 & 3.9 ng/ml2. By 2002, it had become conventional practice to use age-adjusted normal ranges. Some argue about which test method is best; of utmost importance, however, is that a lab verify and properly control an adequate test system. This test refers most commonly to "total PSA [tPSA]". But be aware1that the serine protease PSA circulates in serum in multiple molecular forms consisting of free (unbound to other proteins) PSA (fPSA) and various proteins (about 75% is irreversibly bound to the protease inhibitor alpha-1 antichymotrypsin in a covalent 1:1 molar ratio that creates an enzymatically inactive complex. And there are other complexes. Most of free PSA exists as 3 isoforms (BPSA, proPSA, & "intact fPSA"1. The tPSA value as a numerator can be divided by gland volume and thereby relate the tPSA level to gland size...the calculation producing the "PSA density" or PSAD (a normal value being less than 0.10 to 0.15...below 0.15 is comforting, 0.15-0.18 is concerning, & 0.18 or higher warrants a biopsy) where values greater than 0.15 are said to increase the odds that the patient has PCa1. "PSA velocity" attempts to account for the very steady tendency for PSA to gradually rise with age and increasing BPH (benign gland enlargement)1. It is of greatest help when one has at least three tPSA results over a period of at least 2 years1. One is more concerned that a rising PSA is due to PCa if the increase is greater than 0.75 ng/mL per year1, the NCCN guideline "normal" being no greater than 0.5 in 20073(and Dr. Catalona expecting in 2007 that this will be reduced to a cutoff of 0.35-0.4 ng/mL/year...noting that there is a high death rate among those with a velocity of 2ng/mL/yr or higher in the year prior to diagnosis3).  
Prostate Cancers...2
PSA rangeNo. screenedNo. Bx'edProstate Cancer
No. FoundExpectedMissed
0-2.9 ng/ml6801 85365 211 (3.1%) 146 (69.2%)
0-0.9 ng/ml3045 1834 34  (1.1%) 30 (88.2%)
1.0-1.9 ng/ml2663 46838 96 (3.6%) 58 (60.4%)
2.0-2.9 ng/ml1093 20223 81 (7.4%) 58 (71.6%)
3.0-3.9 ng/ml642 15941 77 (12.0%) 36 (46.8%)
≥4.0 ng/ml1178 1094 319336 (28.5%) 17 (5.1%)
4.0-9.9 ng/ml980 908 213222 (22.7%) 9 (4.1%)
≥10 ng/ml198 186 106114 (57.6%) 8 (7.0%)
          
total8621 2106 425624 (7.2%) 199 (31.9%)

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Associations with PSA level not elevated:

  1. a man negative for Pca

  2. a man positive for Pca

  3. bed rest can cause a decrease

  4. exercise

  5. digital rectal exam (DRE)

Associations with elevated PSA levels:

  1. acute bacterial prostatitis

    .
  2. prostate cancer.
  3. "PSA bounce" may be seen in seed-implant PSA follow-up...in as many as 35% of patients. Within a year or two after seed implantation (median 18 months), the PSA having been down, starts to rise for 12 months or more, the median PSA increase being 0.4 ng/ml, with a range of 0.1 to 15.8 ng/ml. About 22 percent of the men had more than one bounce. Biopsies are problematic because cancer cells which have been shocked but not yet eliminated can be seen in the biopsy in "bounce" situations and don't really mean recurrence. A true cancer recurrence rise happens later, at a median of 30 months after seed implant.
  4. chronic prostatitis of any variety: we had 12 excellent cores & complete info on a 53 y/o friend with rising PSA (his PSA velocity 1.16 [tend to biopsy if PSAV is above 0.6-0.75]) for a doubling time of 1.82 years (tend to biopsy when PSADT is 2 or less). TRUS showed a gland volume of 21.8cc for a PSA density of 0.27 (increased likelihood of cancer

    when above 0.15).
  5. prostatic hyperplasia (BPH)

  6. some men have a high level for no known cause

  7. rarely, a man will carry antibodies toward a component of the test system reagent derived from another animal specie (a heterophile antibody)...all other factors staying equal, this type of elevation should be very stable.

  8. acute urinary retention (can raise it for upwards of 6 weeks)

  9. ejaculation (can raise it for 24-48 hours)

  10. cystoscopy

  11. prostatic massage

  12. cycling

  13. perineal or transrectal needle biopsy.

  14. transrectal ultrasound.

  15. transrectal resection of the prostate.

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Total PSA: Age bracket "normals":

Age Range PSA value units
< 49 years 0.0 - 2.5 ng/mL
50 - 59 years 0.0 - 3.5 ng/mL
60 - 69 years 0.0 - 4.5 ng/mL
> 70 years 0.0 - 6.5 ng/mL

Free & Total PSA

A general rule-of-thumb is that a free PSA < 15% raises concern for cancer and > 25% significantly favors hyperplasia (BPH).  This splitting of PSA into free and total works best when the total PSA is between 4 and 10, when using age bracket normal ranges, and in cases where the man's prostate digital rectal examination (DRE) is "normal" (for example, the effects of a small volume of cancer can be obscured amongst the effects of a gland quite enlarged by BPH). 

Probability of Prostate Cancer (For Men with Non-Suspicious DRE Results and PSA Between 4 and 10 ng/mL, by Patient Age)

% free PSA

Patient Age

50 to 64 Years

65 to 75 Years

0.00 to 10.00% 56% 55%
10.01 to 15.00% 24% 35%
15.01 to 20.00% 17% 23%
20.01 to 25.00% 10% 20%
≥ 25.01% 5% 9%
Probability of Prostate Cancer, Based on PSA and Percent free PSA Results (for Men with Non-Suspicious DRE Results, Regardless of Patient Age)
PSA Probability of Cancer   Percent free PSA Probability of Cancer
0 - 2 ng/mL 1% 0 - 10% 56%
2 - 4 ng/mL 15% 10 - 15% 28%
4 - 10 ng/mL 25% ® ® 15 - 20% 20%
> 10 ng/mL > 50%   20 - 25% 16%
    > 25% 8%

General: (1) low free PSA, especially < 15% = concern for ca. (2) higher free PSA, especially > 25% = favor BPH.

REFERENCES:

  1. ASCP Check Sample...Shariat SF, Roehrborn CG, Wians, FH, Update on PSA Testing for the Early Diagnosis of Prostate Cancer,Clinical Chem. 43(5):71-87. 2003.
  2. Schroder FH, Kranse R, Verification Bias and the PSA Test: Is There a Case for a Lower Threshold for Biopsy NEJM 349(4):393-395.  24 July 2003.
  3. CAP Today, April 2007.

(posted 27 April 2007; latest addition 24 November 2007) [to prostate cancer topics index]

 
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