ELEVATED PROSTATE-SPECIFIC ANTIGEN LEVELS
IN BLACK MEN AND WHITE MEN.
Sawyer R, Berman JJ, Borkowski A, Moore GW.
http://www.netautopsy.org/elevpsal.htm
Send comments and correspondence to:
George.Moore4@med.va.gov
See also:
http://www.medparse.com/gwmcv.htm .............
http://www.medparse.com/psaurol.htm .............
http://www.medparse.com/snomedsp.htm .............
U. S. Government Work, uncopyrighted, published as:
Sawyer R, Berman JJ, Borkowski A, Moore GW.
Elevated prostate-specific antigen levels in black men and white men.
Mod Pathol. 1996 Nov;9(11):1029-1032.
PMID: 8933511.
PubMed Entry
Full Text of Article:
http://www.netautopsy.org/elevpsal.htm
ABSTRACT.
The usual ranges for PSA (Prostate Specific Antigen) are derived from
a community-based population of white men, but are employed for screening
on all men, on the assumption that different PSA levels among different
ethnic groups would be small or would have no clinical significance.
However, recently published reports suggest that PSA levels
in a racial population may vary directly with the relative risk
of prostate cancer within the population. PSA ranges were determined
in African-American and white men registered in the
Veterans Affairs Maryland Health Care System. The total patient census
of 122,602, has near-equal numbers of African-American and white men,
and maintains records of race designation for inpatients. Among patients
with no known prostate cancer, there were 10,808 patients age 40 or older,
and 19,482 PSA tests. Among these patients, there were 3,274 patients
identified as African-American, 2,993 patients identified as white
not of Hispanic origin, and 4,541 patients of other race or race unknown.
The 95th percentile PSA value in African-American men and white men,
respectively, for ages 40-49 is 2.80 and 2.01; for ages 50-59 is 5.40
and 4.19; for ages 60-69 is 9.59 and 7.00; for ages 70-79 is 15.45 and 9.40;
and for ages 80 and over is 21.05 and 18.25. At every age group,
African-American men had a higher range (for the 95th percentile)
than white men. The largest difference is found in men aged 70-79,
where the ratio of the upper limit of PSA for African-American men
compared to white men is 1.6.
Keywords: PSA, prostate-specific antigen, ethnic, race, black,
African-American, screening, range
INTRODUCTION.
PSA is an increasingly popular screening test for prostatic cancer.
Recently, hospitals have reported a many-fold increase in the use
of PSA testing, with a subsequent increase in newly diagnosed prostate
cancers
1
(1).
African-American men have one of the highest prostate cancer rates worldwide and have a 50% higher age-adjusted incidence of prostate cancer than white men
2
(2).
Asian men have among the lowest rates of prostate cancer, and there may be as much as a 120-fold difference between the rate of prostate cancer in the lowest risk group (Shanghai, China) and
the highest risk group (African-American men in San Francisco)
2
(2).
Today, the clinically accepted ranges of PSA levels were adapted from data collected from a community-based Minnesota population consisting entirely of white men
3
(3).
In discussing the importance of age-specific ranges, the Mayo Clinic group acknowledged the lack of current information regarding age-specific PSA ranges for African-Americans, Asians and Hispanics
4
(4).
A study of PSA levels in Asian men found a lower range of PSA levels in this population
5
(5),
suggesting that prostate cancer risk may correlate with PSA levels in the population. A recent letter by our group reported that African-American men indeed have higher ranges of PSA than do white Americans
6
(6).
This finding was corroborated in an article published by Morgan et al.
(7).
The present paper details the methods used to arrive at ranges for African-American and white men using a large database.
MATERIALS AND METHODS.
The patient population at the Veterans Affairs Maryland Health Care
System contains near-equal populations of African-American
and white patients. The Decentralized Hospital Computer Program
(now,
VistA
)
retains data and supports queries relating to all recorded demographic data, and laboratory tests for a patient population exceeding 120,000, covering 3 hospitals and a network of outpatient clinics. The PSA levels of African-American and white men were studied to determine the age-based PSA ranges for this population. Data were collected using the VA File Manager, version 22, used by nearly all 172 Veterans Affairs medical centers nationwide. Centralized registration of patients with unique identification numbers insures that patients are not entered redundantly, and that all patients have database registration. Laboratory information (including any and all PSA tests results and the date of test) is linked with the patient identifier and stored in perpetuity. Patient age at the time of a PSA test is computed as the difference between the test date and the listed date of birth. Race/ethnicity is recorded according to a classification established by the United States Public Health Service, in which all patients are assigned one of six categories, as follows: 1) Black, not of Hispanic origin; 2) White, not of Hispanic origin; 3) Hispanic; 4) Asian or Pacific Islander; 5) American Indian or Alaskan Native; 6) Other.
There were 12,548 patients who received one or more PSA determinations
(Hybritech) between October 1, 1989, and January 23, 1996, as part
of their routine medical care. Among these, 11,125 patients had
no diagnosis of prostate cancer, and 10,808 patients were at least
40 years old. Patients had received between one PSA test (6,538 patients)
and 19 PSA tests (1 patient), as shown in Table 1, for a total
of 19,482 tests. In order not to bias the final results in favor
of patients with many PSA determinations, each PSA test was weighted
1/n if the same patient had n PSA tests after age 40.
Thus, in a patient receiving one PSA test at age 48 and another PSA test at age 52, each test is weighted as a half-patient. Since some patients had PSA tests taken in consecutive decades of life in our database, this weighting procedure resulted in 'fractional patients' in some decades.
For each race (African-American and white) and each decade of life over 40 years old, MEAN PSA VALUE was calculated as the sum of all PSA values, divided by the number of PSA values (appropriately weighted for fractional patients). The MEDIAN PSA VALUE
(same as 50th percentile PSA value) was calculated as that value with half the observed PSA values below the median and half the observed PSA values above the median. Similarly, the 90th PERCENTILE PSA VALUE was calculated as that value with 90% of observed PSA values below the 90th percentile and 10% of observed PSA values above the 90th percentile; and similarly for the 95th PERCENTILE PSA VALUE. Because of the large number of observed data points (circa 3,000 for either race), medians and percentiles were calculated directly rather than through estimates on a regression, as used by the Mayo group
(4).
RESULTS.
On January 23, 1996, the cumulative patient census at the
Veterans Affairs Maryland Health Care System was 122,602.
Among these subjects, 10,808 had received one or more PSA determinations
between October 1, 1989, and January 23, 1996, had no diagnosis
of prostate cancer, and were age 40 or older. Among these patients,
there were 3,274 patients identified as African-American,
2,993 patients identified as white not of Hispanic origin,
and 4,541 patients of other race or race unknown
(Table 2).
The PSA ranges for these patients are listed in
Table 3.
For every age group studied, African-American men had equal
or higher mean, median, and 90th and 95th percentile PSA tests
than did white men.
Our study showed 95th percentile PSA value in African-American men
and white men, respectively, for ages 40-49 is 2.80 and 2.01;
for ages 50-59 is 5.40 and 4.19; for ages 60-69 is 9.59 and 7.00;
for ages 70-79 is 15.45 and 9.40; and for ages 80 and over
is 21.05 and 18.25
(Figure 1).
The upper limit for PSA is defined as the 95th percentile for each age range.
In the study by the Mayo Clinic group, this number was calculated
for the midpoint of the age range from a regression analysis
of their data points within each age range. This statistical
representation of the 95th percentile was necessary because
of the small population size under study. For example,
the 95th percentile group for persons in the 70-79 age group
contained only 5 subjects in the Mayo Clinic study,
as compared to 788.4 African-Americans and 993.23 white non-Hispanics
in the present study. Thus in the current study, there are
over 6,000 subjects with known race, permitting a direct determination
of the 95th percentile score from the data set.
DISCUSSION.
All the data employed in this study were available from a single source,
namely, the Decentralized Hospital Computer Program in the Veterans Affairs
Maryland Health Care System. The final patient population was obtained
after subtracting away patients with no PSA tests, patients with no race
identifier and patients with known prostatic cancer, all data contained
within the DHCP. It included patients whose PSA was obtained as part
of screening (based on age), as well as patients whose PSA was obtained
as part of the clinical work-up of symptoms relating to non-neoplastic
urologic conditions. The data obtained are relevant to patients received
in a medical system that includes three hospitals and an extensive
outpatient clinic system serving a population of military service veterans.
As such, our data may not be representative of other patient populations
with a different range and prevalence of individuals
with urologic complaints.
Large, well-maintained patient databases insure that all patients
are included uniquely, that all laboratory tests, including
surgical pathology, cytology, and autopsy reports (in the case of deaths)
are stored and linked to the patient identifier, and in that
basic demographics, including race, are available. Such databases
are a tremendous resource to the medical community and can be used for
epidemiologic studies
(8).
In studies that collect PSA levels in a population extending
over a period of time, single patients accumulate multiple PSA values
(Table 1).
This necessitates a reasonable method for scoring PSA values
in a percentile calculation. This task is further complicated
by the need to stratify PSA values by age, as a single patient
might have had PSA values sampled in different decades. A recent study
of PSA levels in a population published by Morgan et al.
ignored all PSA tests other than the first test performed on each patient
(7),
resulting in the removal of about 30,000 PSA values, representing
about 2/3 of their collected data. In this study, we retained
each data entry by giving each PSA test a weight of
1/n,
where
n
is the number of PSA tests for the patient. Thus, in a patient receiving one PSA test in one decade of life and another PSA test in the subsequent decade, each test is weighted as half a patient. For patients with PSA tests taken in consecutive decades of life in our database, this weighting procedure resulted in 'fractional patients' in some decades
(Table 2).
This weighting technique has the advantage of using all the data,
and avoids the bias caused by excluding a test result from analysis.
Several methods have been proposed for determining the upper limit
of a PSA value, i.e., the value at which an immediate clinical action
should be considered. A recent abstract that addressed the issue
of PSA values based on race examined a large number of cases culled
from over 250 centers. Their study reported whites had a higher mean
PSA value than did African-Americans, a result that would seem
to contradict our findings (9).
To determine a useful range of test values for a population,
percentile-statistics are preferable to the mean-statistic,
since the latter is easily skewed by a few, large outlier values.
For example, in
Table 3,
the high mean value for African-Americans at least 80 years old (623.81)
is due to a single PSA value over 100,000 ng/ml. In all likelihood,
this patient has an undiagnosed prostate cancer. In contrast,
the percentile values for the same group of patients are only
slightly skewed (circa 1 ng/ml) by this single outlier value.
Traditionally, the 95th percentile value is used as the upper limit
in many clinical laboratory tests, i.e., tolerance of 5% false
positive values. In the current study, there are circa 3,000 subjects
in either racial group, permitting a direct determination
of the 95th percentile score from the data set.
The current study demonstrates that African-Americans have a higher range
of PSA levels than do white Americans, and has been corroborated by data
from another large study involving patients registered
at Walter Reed Army Medical Center (7).
The biological and clinical interpretation of these observations
is unknown at present. A higher range of PSA levels in the
African-American population might indicate a high number
of undiagnosed prostate cancers among this group, prompting
close surveillance of African-American men with PSA levels
greater than 4.0 ng/ml (the PSA level currently used to prompt
clinical action). Alternately, the higher PSA levels
in African-American men might indicate that African-American men
without prostate cancer may have high PSA levels, possibly
due to a higher incidence of prostatic hyperplasia,
increased PSA "leakiness", increased incidence of prostatic infarction,
or any non-neoplastic condition that might elevate PSA spuriously.
If this were the case, a higher screening threshold should be used
for African-Americans, since it can be assumed that many disease-free
African-American men have high PSA levels. The correct clinical
interpretation of the data presented in this study lies in knowing
the number of men in the disease-free group who in fact have
undiagnosed cancer. No study to date has addressed this question,
and the proper clinical response to a high PSA level
in an African-American man is currently a matter of judgment,
not experimental evidence.
ACKNOWLEDGMENTS.
We are grateful to Dr. Robert Burger, VA Surgery Service, who initiated
the project by requesting that Pathology Service provide the PSA ranges
for African-American men.
REFERENCES.
1. Berman JJ, Alonsazana, Brown L, Moore GW.
PSA screening for prostate cancer: lack of reduction in Gleason scores.
Mod Pathol. 1994;7:487-489.
2. Meilke AW, Smith JA.
Epidemiology of prostate cancer.
Urol Clin North Am. 1990;17:709-718.
3. Oesterling JE, Jacobsen ST, Chute CG, Guess HA,
Girman CJ, Panser LA, Lieber MM.
Serum prostate-specific antigen in a community-based population
of healthy men.
JAMA. 1993;270:860-864.
4. Oesterling JD, Jacobsen SJ, Cooner WH.
The use of age-specific reference ranges
for serum prostate specific antigen in men 60 years old or older.
J Urol. 1995;153:1160-1163.
5. Oesterling JE, Kumamoto Y, Tsukamoto T, Girman CJ,
Guess HA, Masumori N, Jacobsen SJ, Lieber MM.
Serum prostate specific antigen in a community-based population
of healthy Japanese men: lower values than for similarly aged white men.
Br J Urol. 1995;75:347-352.
6. Sawyer R, Berman JJ, Borkowski A, Moore GW.
Prostate-specific antigen in black men.
Lancet (letter) 1996;347:1329.
7. Morgan TO, Jacobsen SJ, McCarthy WF,
Jacobson DJ, McLeod DG, Moul JW.
Age-specific reference ranges for prostate-specific antigen (PSA)
in black men.
New Engl J Med 1996;335:304-310.
8. Berman JJ, Moore GW.
SNOMED-encoded surgical pathology databases:
A tool for epidemiologic investigation.
Mod Pathol. 1996 Sep;9(9):944-950.
PMID: 8878028.
PubMed Entry
Full Text of Article:
http://www.netautopsy.org/snomedsp.htm
9. DeAntoni EP, Crawford DE, Ross CA, Hirano D, Blum DS,
Berger ER, Stone NN, Eisenberger MA, Gambert SR, McLeod DG, Staggers F.
Age and race-specific reference ranges for prostate-specific antigen
from a large, community-based study (abstract).
Proc Amer Urol Assoc. 1996;155:374A.
10. Berman JJ, Moore GW, Alonsozana ELC, Mamo GF.
Elevated prostate-specific antigen level
and the negative prostate biopsy.
South Med J. 1994 Feb;87(2):290-291.
PMID: 7509507.
PubMed Entry
Full Text of Article:
http://www.netautopsy.org/psaurol.htm
11. Berman JJ, Alonsazana, Brown L, Moore GW.
Prostate-specific antigen screening for prostate cancer:
No reduction in Gleason scores.
Mod Pathol. 1994 May;7(4):487-489.
PMID: 7520587.
PubMed Entry
TABLE 1.
DISTRIBUTION OF MULTIPLE PSA TESTS PER PATIENT,
WITH NO DIAGNOSIS OF PROSTATE CANCER.
Number of Number of Cumulative Cumulative
PSA Tests Patients Patients Tests
1 ............ 6,538 ...... 6,538 ...... 6,538
2 ............ 2,156 ...... 8,694 ...... 10,850
3 ............ 1,081 ...... 9,775 ...... 14,093
4 ............ 525 ...... 10,300 ...... 16,193
5 ............ 214 ...... 10,514 ...... 17,263
6 ............ 121 ...... 10,635 ...... 17,989
7 ............ 67 ...... 10,702 ...... 18,458
8 ............ 39 ...... 10,741 ...... 18,770
9 ............ 23 ...... 10,764 ...... 18,977
10 ............ 20 ...... 10,784 ...... 19,177
11 ............ 10 ...... 10,794 ...... 19,287
12 ............ 6 ...... 10,800 ...... 19,359
13 ............ 2 ...... 10,802 ...... 19,385
14 ............ 2 ...... 10,804 ...... 19,413
15 ............ 1 ...... 10,805 ...... 19,428
16 ............ 0 ...... 10,805 ...... 19,428
17 ............ 1 ...... 10,806 ...... 19,445
18 ............ 1 ...... 10,807 ...... 19,463
19 ............ 1 ...... 10,808 ...... 19,482
TABLE 2.
PATIENT DEMOGRAPHICS FOR THE STUDY SET OF 10,808 PATIENTS
Total number of patients in Baltimore VAMHCS database.... 122,602
Patients, at least one PSA test, no prostate cancer...... 11,125
Patients, at least one PSA test, no prost ca, >40 ....... 10,808
African-American ..................................... 3,274
White ................................................ 2,993
Other race or race not stated ........................ 4,541
African-American White
Men Men
Age 40-49.................. 614.83 ......... 283.50
Age 50-59.................. 504.30 ......... 380.68
Age 60-69.................. 1250.31 ......... 1182.28
Age 70-79.................. 788.40 ......... 993.23
Age >80.................... 116.17 ......... 153.31
Total .................... 3274 ......... 2993
TABLE 3.
PSA LEVELS IN AFRICAN-AMERICAN AND WHITE MEN
Mean PSA Median PSA 90%ile 95%ile
(50%ile)
Ages 40-49
black 1.21 1.00 1.72 2.80
white 1.05 1.00 1.70 2.01
ratio 1.2 1.0 1.0 1.4
Ages 50-59
black 1.84 1.00 3.05 5.40
white 1.79 1.00 3.05 4.19
ratio 1.0 1.0 1.0 1.3
Ages 60-69
black 3.97 1.50 6.10 9.59
white 2.26 1.30 4.60 7.00
ratio 1.8 1.2 1.3 1.4
Ages 70-79
black 5.08 2.00 8.70 15.45
white 4.04 1.65 6.20 9.40
ratio 1.3 1.2 1.4 1.6
Ages >80
black 623.81 2.40 12.40 21.05
white 12.30 2.12 9.52 18.25
ratio 50.7 1.1 1.3 1.2
Last updated: 9/15/2005, by G. William Moore, MD, PhD.