PSA Level, 'free-PSA' and Prostate Cancer

PSA or prostate specific antigen is a blood test that measures a 'chemical' released by the prostate. It is found in   low levels in normal men and is not elevated with other forms of cancer. The AUA recently published guidelines on using PSA (Oncology 2000;14:267.)

PSA Levels in Normal Men by Age

Age PSA Age PSA
40 - 44y 1.9 60 - 65y 5.3
45 - 49y 2.6 65 - 69y 6.0
50 - 54y 3.2 70 - 74y 6.6
55 - 59y 4.3 75y + 7.5

Age Specific PSA Ranges by Race
Age Range White African-American
40 -49y 0 - 2.5 0 - 2.0
50 - 59y 0 - 3.5 0 - 4.0
60 - 69y 0 - 4.5 0 - 4.5
70 - 79y 0 - 6.5 0 - 5.5

The distribution of PSA levels by stage and in normal men is shown. Note that normal men may have slight elevations but even with an enlarged gland (hypertrophy) only 2% of the time is the PSA over 10. Also note that even with advanced stage D cancer, 12% of the men may have a normal PSA (0 - 4) so the test is far from fool proof.
PSA: 0 - 4 4 - 10 > 10
Normal Men 99% 1% 0%
Hypertrophy (BPH) 80% 18% 2%
Stage A Cancer 37% 33% 30%
Stage B Cancer 29% 21% 50%
Stage C Cancer 19% 9% 72%
Stage D Cancer 12% 9% 79%

The higher the PSA, the more likely a biopsy will show cancer. In men over 50 the odds that a biopsy will show cancer are: 27% (PSA 2.5 - 4.0), 20-30% (PSA > 4), 42-67% (PSA > 10.) (also see 'free-PSA'   below)

The higher the level of PSA, the less likely that the cancer is still confined to the gland. Data on 4,133 men who underwent surgery (JAMA 1997;227:1448) showed that the percent of men with cancer found to be contained to   within the capsule of the gland fell dramatically as the PSA rose, so that if the PSA was over 10 prior to surgery, the odds that cancer was confined was less than 35%
PSA Confined to gland PSA Confined to gland
0 - 4 64% 30.1 to 40 16%
4.1 to 10 50% 40.1 to 50 13%
10.2 to 20 35% > 50 9%
20.1 to 30 18%    

If the PSA is low it is generally not necessary to obtain a bone scan or CAT scan when evaluating a cancer patient (according to the AUA guidelines.) The odds that a bone scan will be positive based on the PSA: 0.8% (PSA < 10), 0.6% (PSA 10.1 - 15) and 2.6% (PSA 15.1 - 20.) Similarly a CAT is not indicated to look for nodes unless the PA is > 25. The accuracy of CT at picking up positive nodes is poor (only 30-35% and MRI only 35%) anyway.

The pattern of a rising PSA after surgery or radiation is helpful in predicting the type of relapse.  It is rises within 12 mos of treatment or double in less than 6 months that indicates metastases, but if if starts rising after 24 months with a doubling time of > 12 mos it implies a local/regional relapse.

The higher the PSA the less likely that radiation alone or surgery will cure the patient, if cure is defined as getting the patients PSA after treatment to a very low level (< 1) and having the PSA stay low. The relapse rate after external beam radiation based on the level of the PSA from 500 cases at the Mayo Clinic (Cancer 1997;79:341) is as follows:
PSA Level Relapsed after Radiation
0.1 to 4 4%
4 to 10 7%
10 to 20 22%
20 - 50 48%
over 50 67%
 

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Even in men with favorable Gleason score less than 7) and early stage, a PSA over 30 predicts a very poor cure rate with radiation alone and the need to combine radiation with hormone therapy (i.e. androgen blockage like Lupron/Casodex)

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After completing radiation the PSA will slowly drift lower but commonly does not reach its low point (PSA nadir) for 12 to 24 months. The lower it goes the better. The risk of a relapse is related to how low the PSA goes as noted in a recent study: (J. Urolo 1996;156:450)
PSA Nadir Control Rate (bNED/3y)
< 1 93%
1 - 1.99 49%
2+ 16%
 
Another test commonly used is the 'free-PSA'. It was found that patients with cancer have a lower free PSA than patients without cancer (in one study 9% cancer versus 19% non-cancer and in another 13% cancer versus 17% non-cancer.) In patients with a slight PSA elevation (between 4 and 10) some urologists will use the 'free-PSA' to decide who to biopsy (for instance only biopsy those whose free-PSA is less than 20-25%) The lower the free-PSA the more likely cancer as noted below:)

Biopsy Results with PSA 4-10, based on Free-PSA percentage
Percent Free PSA % with Cancer
0 - 10% 56%
10 -15% 28%
15-20% 20%
20-25% 16%
>25% 8%

Odds of Cancer in Men With Normal Feeling Gland and PSA between 4 and 10
% Free PSA Age 50-64y Age 65-75y
0 - 10% 56% 55%
10.1 - 15% 24% 35%
15.1 - 20% 17% 23%
20.1 - 25% 10% 20%
over 25% 5% 9%