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Prostate Cancer and African-American Men
Published on Physicians Practice (http://www.physicianspractice.com)
Prostate Cancer and African-American Men
Review Article [1] | May 01, 1997
By Judd W. Moul, MD [2]
Dr. Powell is to be congratulated for an outstanding review article on prostate cancer in
African-American men. As he points out, the age-adjusted incidence of prostate cancer in
African-American (black) males is 50% higher than that in Caucasian (white) men, and black men
have the highest incidence of prostate cancer in the world.[1] Differences between blacks and whites
in the probability of being diagnosed with prostate cancer (9.6% vs 5.2%), lifetime prostate
cancer-specific mortality (3% vs 1.4%), and 5-year survival (65% vs 78%) are all indicative of a major
public health problem in the black male population.[2]
Dr. Powell is to be congratulated for an outstanding review article on prostate cancer in
African-American men. As he points out, the age-adjusted incidence of prostate cancer in
African-American (black) males is 50% higher than that in Caucasian (white) men, and black men
have the highest incidence of prostate cancer in the world.[1] Differences between blacks and whites
in the probability of being diagnosed with prostate cancer (9.6% vs 5.2%), lifetime prostate
cancer-specific mortality (3% vs 1.4%), and 5-year survival (65% vs 78%) are all indicative of a major
public health problem in the black male population.[2]
The etiology for these racial differences in the clinical behavior of prostate cancer is unknown;
hormonal, nutritional, genetic, behavioral, and socioeconomic status factors have all been
implicated.[2] Now, in the late 1990s, as more research funding is finally being devoted to prostate
cancer, it is critically important to find the cause or causes of this racial disparity. Our research
group, the Department of Defense (DoD) Center for Prostate Disease Research (CPDR), is funded to
study prostate cancer and disease in the DoD health-care system. Because the CPDR has a mandate
to study an equal-access, geographically diverse system that provides health care for a large
number of African-American men, it is a good setting in which to investigate this issue. I will review
our ongoing investigations in this area and compare/contrast our findings to Dr. Powell's exemplary
work.
Use of PSA in Black Men
Despite the racial disparity noted above, encouraging recent data from the Radiation Therapy
Oncology Group (RTOG),[3] US military,[4] and Veterans Administration[5] suggest that if black men
are afforded the same access and medical care as white men, the outcome disparity may be
minimized or eliminated. Armed with this information, we may be able to affect prostate cancer in
this population with increased public awareness, early detection programs, and proper detection
tools.
For a number of years, the American Urological Association (AUA), American Cancer Society (ACS),
and American College of Radiology have recommended that early detection programs using digital
rectal examination (DRE) and prostate-specific antigen (PSA) be started at age 40 in
African-American men. Despite this recommendation, until now, no data existed to document the
value of PSA testing for the early and accurate diagnosis of prostate cancer in this population. The
finding by our group and others that black men with prostate cancer had higher PSA values at
diagnosis, even after adjustment for patient age and tumor stage, grade, and volume,[6] created an
urgent need to examine the proper PSA "normal" ranges for black men.
Age-Adjusted References Ranges for Black Men
Our article, "Age specific reference ranges for serum prostate specific antigen in black men,"
published in the August 1, 1996, issue of the New England Journal of Medicine documents the
outstanding ability of PSA to detect prostate cancer in both Caucasian and African-American men
and develops age-adjusted PSA reference ranges for maximal cancer detection in this high-risk group
of men.[7] In this study, between January 1991 and May 1995 serum PSA concentration was
determined for 3,475 men without clinical evidence of prostate cancer (1,802 Caucasian, 1,673
African-American) and 1,783 men with prostate cancer (1,372 Caucasian, 411 African-American). All
PSA examinations were performed in a central, single laboratory using the Abbott IMx assay (normal,
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Prostate Cancer and African-American Men
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0 to 4 ng/mL).
Prostate-specific antigen concentration was analyzed as a function of age and race to determine the
operating characteristics of PSA for the diagnosis of prostate cancer. Serum PSA concentration
correlated directly with age for both African-American and Caucasian men (r = .40, P = .001 for
African-Americans; r = .34, P = .0001 for Caucasians). African-American men had significantly higher
serum PSA concentrations than Caucasian men (P = .0001)(Figure 1). When sensitivity was plotted
against specificity, the area under the receiver-operator-characteristic (ROC) curve was .91 for
African-American men and .94 for Caucasian men, indicating that the PSA test is an excellent early
detection tool. For comparison, the Pap smear for cervical cancer, which is an accepted clinical
screening test, has an ROC value of only .70.
When we calculated age-specific PSA reference ranges by the identical methodology used by
Oesterling and colleagues in their 1993 study of Olmstead County, Minnesota,[8] we found very
similar values for white men but higher values for black men. These ranges were 0 to 2.4 ng/mL for
black men age 40 to 49, 0 to 6.5 ng/mL for men age 50 to 59, 0 to 11.3 ng/mL for men age 60 to 69,
and 1 to 12.5 ng/mL for men age 70 to 79. We then tested these new ranges in our group of black
men with prostate cancer to determine how the ranges would have performed if they had been used
to detect the cancers. Unfortunately, these markedly higher ranges would have missed 41% of the
cancers (sensitivity of only 59%).
The reason that these traditionally derived ranges performed so poorly is simple: They represent the
95th percentile of values in the black controls. Because there is more variability of PSA results in
blacks without evidence of cancer, there is more skewness, which pushes the 95th percentile farther
to the right (higher). This higher range, however, is not clinically useful. Accordingly, we developed
age-adjusted reference ranges for black men with prostate cancer, selecting upper limits of normal
PSA by decade to maximize cancer detection. In other words, we developed reference ranges by
decade in the men with prostate cancer by using the fifth percentile of PSA values. Only the lowest
5% of prediagnosis PSA values in the black men with cancer are "normal," and the remainder (95%)
are above normal (95% sensitivity).
We call these ranges the Walter Reed/Center for Prostate Disease Research (WR/CPDR) age-specific
reference ranges for maximal cancer detection (Table 1). They maximize sensitivity (cancer
detection) without undue loss of specificity (false-positive results, unnecessary transrectal
ultrasound/biopsy). These values for maximal cancer detection for black and white men are
compared to the traditional normal ranges (0 to 4 ng/mL) and the previously developed age-specific
reference ranges in Table 2. Now that we have shown that PSA is an outstanding tool for prostate
cancer detection in African-American men, as well as in Caucasian men, we need to promote public
awareness and encourage African-American men to be tested, such as Dr. Powell and colleagues did
in their landmark Detroit Education and Early Detection (DEED) study.
Is African-American Race a Prognostic Factor for a Worse Outcome?
There is an ongoing debate as to whether African-American race, itself, is a prognostic factor for
worse outcome in men with localized (and advanced) prostate cancer. As noted above, data from the
RTOG,[3] US military,[4] and Veterans Administration[5] suggest that race alone is not a prognostic
factor. Conversely, a recent Surveillance, Epidemiology, and End Results (SEER) database study in
metropolitan Detroit found that, at all stages of disease, blacks had a poorer survival than whites;
this was especially evident in younger men (less than 65 years of age).[9] Powell et al also found
that survival was worse for African-American men under age 65 but better for men over age 65, and
used the phrase, "ethnic survival crossover," to describe this phenomenon. More study needs to be
done to determine whether younger black men do have a worse survival, and, if so, what causes this
disparity.
In an attempt to answer these questions, our group has been comparing outcome and tumor
characteristics by race among men who have undergone radical prostatectomy. In a consecutive
group of 91 radical prostatectomy patients, 28 (30.8%) of whom were African-American, blacks had
higher tumor volumes in all clinical stage categories (Table 3).[6] Overall, the black men had a mean
tumor volume of 5.42 cc, as compared with a volume of 2.10 cc in the white patients. This greater
tumor volume was associated with more adverse pathologic features of the radical prostatectomy
specimens and worse outcome.
In a follow-up study, we compared 518 black and white men who had undergone radical
prostatectomy at Walter Reed Army Medical Center between 1975 and 1995.[10] Table 4 compares
the pathologic variables of the radical prostatectomy specimens in these two groups. There were
nonsignificant trends for blacks to have higher pathologic stage and Gleason grade. Most strikingly,
the margin-positive rate was 50.5% in blacks, as compared with 38.4% in whites (P = .038). These
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statistics are very similar to those reported by Powell and associates.
Our survival analysis for black and white men was very interesting and points to the need for careful
multivariate analysis when trying to determine whether race is a prognostic factor. Overall, the
African-American men had a lower recurrence-free survival. In other words, at a mean follow-up of
23.3 months, black men were more likely to have had a recurrence (defined as a rising PSA as the
first evidence of failure). Even in one multivariate analysis that adjusted for pathologic stage, grade,
and pretreatment PSA and acid phosphatase, black race remained an independent prognostic factor.
However, in another multivariate analysis that included margin positivity in the model, race was no
longer an independent prognostic factor (P = .083).
Because clinical stage and pathologic stage categories may not accurately reflect tumor volume and
subtle pathologic features, such as margin positivity and volume of high-grade cancer, it will be
imperative to include these factors in any multivariate analysis aimed at determining whether race
affects outcome. The Armed Forces Institute of Pathology and CPDR are currently collaborating on a
prospective radical prostatectomy study to compare three-dimensional tumor volumes and careful
quantitative histology with outcome in black and white men.
Is Biology or Behavior and Access to Blame for the Poor Pathologic Findings?
Even if race itself is not found to be an independent prognostic marker when these comprehensive
pathologic assessments are included, we will still be left with the question of what is responsible for
the worse pathologic findings in black men. Considering that the black men in our studies were 1 to
3 years younger than the white men and yet have bigger tumors with more adverse pathologic
features, is biology or behavior and access to blame? My own bias is that behavior and access are
largely at fault. African-American men simply have not been educated about prostate cancer and the
need for early detection. If early detection programs were more universally available to black men
starting at age 40 and were accepted, I believe that we would detect the majority of prostate
cancers when they were smaller and with fewer adverse pathologic features and would eliminate the
current racial survival disparity.
This contention appears to be borne out by the early DEED study results obtained by Powell and
associates. Compared to a nonscreened population, the screened African-American men undergoing
radical prostatectomy had a significantly higher rate of organ-confined disease and lower recurrence
rate at early follow-up. By instituting education about prostate cancer and screening PSA in this
high-risk population, the DEED project increased the organ-confined rate in these men to 65%--a
gratifying result. Furthermore, at a mean follow-up of 18 to 20 months, of the 15 DEED men
screened who underwent a radical prostatectomy, only 1 (7%) suffered a recurrence, as compared
with 25% of the nonscreened clinic patients.
Also encouraging was the finding that the DEED screened men had lower mean and median initial
PSA values. Considering that pretreatment PSA correlates directly with tumor volume in both black
and white radical prostatectomy patients,[6] the DEED data suggest that screened African-American
men are being diagnosed when their tumors are smaller. It is tantalizing to speculate that if we use
the lower PSA reference range of 2.0 ng/mL developed by WR/CPDR in men between 40 to 49 years
old, as discussed earlier,[7] and encourage screening in these younger African-American men, we
can have even a greater impact.
Finally, I strongly agree with Dr. Powell that based on the DEED data, we cannot afford to wait to
promote early detection in this high-risk population of African-American men.
References:
1. Boring CC, Squires TS, Health CW: Cancer statistics for African Americans: 1992. CA Cancer J Clin
43:7-17, 1993.
2. Morton RA: Racial differences in adenocarcinoma of the prostate in North American men. Urology
44:637-645, 1994.
3. Roach M, Won M, Keller J, et al: The prognostic significance of race and survival from prostate
cancer based on patients irradiated on Radiation Therapy Oncology Group Protocols (1976-1985). Int
J Radiat Oncol Biol Phys 24:441-449, 1992.
4. Optenberg SA, Thompson IM, Friedrichs P, et al: Race, treatment, and long-term survival from
prostate cancer in an equal-access medical care delivery system. JAMA 274:1599, 1995.
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Prostate Cancer and African-American Men
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5. Fowler JE, Terrell F: Survival in blacks and whites after treatment for localized prostate cancer. J
Urol 156:133-136, 1996.
6. Moul JW, Sesterhenn IA, Connelly RR, et al: Prostate-specific antigen values at the time of prostate
cancer diagnosis are higher in African-American men. JAMA 274:1277-1281, 1995.
7. Morgan TO, Jacobson SJ, McCarthy WF, et al: Age-specific reference ranges for prostate-specific
antigen in black men. N Engl J Med 335:304-310, 1996.
8. Oesterling JE, Jacobson ST, Chute CG, et al: Serum prostate-specific antigen in a community-based
population of healthy men. JAMA 270:860, 1993.
9. Pienta KT, Demers R, Hoff M, et al: Effect of age and race on the survival men with prostate cancer
in the metropolitan Detroit tri-county area, 1937 to 1987. Urology 45:93-102, 1995.
10. Moul JW, Douglas TH, McCarthy WF, et al: Black race is an adverse prognostic factor for prostate
cancer recurrence following radical prostatectomy in an equal-access health care system. J Urol
155:1667-1673, 1996.
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