From the Pathology and Laboratory Medicine Service,
Veterans Affairs Maryland Health Care System, Baltimore, Maryland [1];
Department of Pathology, University of Maryland Medical System,
Baltimore, Maryland [2]; and
Department of Pathology, The Johns Hopkins Medical Institutions,
Baltimore, Maryland [3].
Sawyer R, Berman JJ, Borkowski A, Moore GW.
Prostate-specific antigen in black men.
Lancet. 1996 May 11;347(9011):1329.
PMID: 8622518.
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George.Moore4@va.gov
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Last tested: July 5, 2009.
0. DISCLAIMER.
DISCLAIMER. United States Government Work, uncopyrighted,
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This document is provided "as is", without warranty of any kind, express
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1. 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.
key words: PSA, prostate-specific antigen, ethnic, race,
black, African-American, screening, range
2. 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). 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).
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).
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).
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).
A study of PSA levels in Asian men found a lower range of PSA levels
in this population (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).
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.
3. 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
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).
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.
5. 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 otherpatient 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.
6. ACKNOWLEDGEMENTS.
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.
7. 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. 17:709-718, 1990.
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 270:860-864, 1993
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;335:304-10.
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.
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: 7/5/2009, by
G. William Moore, MD, PhD.