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I m p a c t o f R a c e o n P r o s t a t e - S p e c i fi c A n t i g e n O u t c o m e A f t e r
Radical Prostatectomy for Clinically Localized
Adenocarcinoma of the Prostate
By Chaundre K. Cross, Delray Shultz, S. Bruce Malkowicz, William C. Huang, Richard Whittington, John E. Tomaszewski,
Andrew A. Renshaw, Jerome P. Richie, and Anthony V. D’Amico
Purpose: To compare prostate-specific antigen (PSA)
outcome after radical prostatectomy (RP) for prostate
cancer in African-American and white men using previously established risk groups.
Patients and Methods: Between 1989 and 2000,
2,036 men (n ⴝ 162 African-American men, n ⴝ 1,874
white men) underwent RP for clinically localized prostate cancer. Using pretreatment PSA, Gleason score,
clinical T stage, and percentage of positive biopsy specimens, patients were stratified into low- and high-risk
groups. For each risk group, PSA outcome was estimated using the actuarial method of Kaplan and Meier.
Comparisons of PSA outcome between African-American and white men were made using the log-rank test.
Results: The median age and PSA level for AfricanAmerican and white men were 60 and 62 years old and
8.8 and 7.0 ng/mL, respectively. African-Americans
had a statistically significant increase in PSA (P ⴝ .002),
Gleason score (P ⴝ .003), clinical T stage (P ⴝ .004), and
percentage of positive biopsy specimens (P ⴝ .04) at
presentation. However, there was no statistical difference in the distribution of PSA, clinical T stage, or
Gleason score between racial groups in the low- and
high-risk groups. The 5-year estimate of PSA outcome
was 87% in the low-risk group for all patients (P ⴝ .70)
and 28% versus 32% in African-American and white
patients in the high-risk group (P ⴝ .28), respectively.
Longer follow-up is required to confirm if these results
are maintained at 10 years.
Conclusion: Even though African-American men presented at a younger age and with more advanced
disease compared with white men with prostate cancer, PSA outcome after RP when controlled for known
clinical predictive factors was not statistically different.
This study supports earlier screening in African-American men.
J Clin Oncol 20:2863-2868. © 2002 by American
Society of Clinical Oncology.
PPROXIMATELY 198,100 new cases of prostate
cancer are expected in the United States during 2001.
Secondary to the introduction of prostate-specific antigen
(PSA) screening, incidence rates increased dramatically
between 1988 and 1992. From 1992 to 1998, AfricanAmerican men were almost two times as likely to be
diagnosed with prostate cancer compared with white men
(234.2/100,000 men v 144.6/100,000 men, respectively).
Incidence rates for African-American men have declined
between 1992 and 1998 by 4.0% per year. However,
white men have experienced more of a decline in
incidence rates during this 7-year period (5.7% per
year).1,2 Also, African-American men were twice as
likely to die of prostate cancer in comparison with white
men between 1992 and 1998 (53.1/100,000 men and
22.4/100,000 men, respectively). From 1994 to 1998,
prostate cancer death rates declined for white and African-American men (4.7% and 3.0%, respectively).1,2
The reason for the discrepancy of worse incidence and
death rates among African-American men in comparison
with white men in the United States is still debated. More
biologic, aggressive cancer has been proposed as one
possible explanation given for the higher PSA level and
younger age at presentation,3-14 as well as more multifocal
disease on autopsy,15,16 higher prevalence of (allegedly)
high-risk alleles, such as CAG repeat,17-20 vitamin D bind-
ing protein,21 and SRD5A2 gene,22 a higher testosterone
level in younger men,23,24 and adverse pathologic factors
after radical prostatectomy (RP)25-29 in African-American men compared with white men. Socioeconomic
factors such as income, education, nutrition, and screening have also been cited as factors contributing to the
more aggressive and advanced stage of prostate cancer in
African-American men.30-33
Studies to date have suggested that when patients with
early-stage prostate cancer are stratified by pretreatment
tumor characteristics, PSA outcome is not different between
ethnic groups.34,35 Limitations of these studies include
A
From the Departments of Radiation Oncology, Pathology, and
Urology, Brigham and Women’s Hospital and Dana-Farber Cancer
Institute, Boston, MA; and Department of Mathematics, Millersville
University, Millersville, and Departments of Urology, Radiation Oncology, and Pathology, Hospital of University of Pennsylvania, Philadelphia, PA.
Submitted November 14, 2001; accepted March 18, 2002.
Address reprint requests to Chaundre Cross, MD, and Anthony
D’Amico, MD, Department of Radiation Oncology, Brigham and
Women’s Hospital, 75 Francis St, L-2 Level, Boston, MA 02215; email:
[email protected]
© 2002 by American Society of Clinical Oncology.
0732-183X/02/2012-2863/$20.00
Journal of Clinical Oncology, Vol 20, No 12 (June 15), 2002: pp 2863-2868
DOI: 10.1200/JCO.2002.11.054
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Copyright © 2002 American Society of Clinical Oncology. All rights reserved.
2863
2864
CROSS ET AL
Table 1.
Pretreatment Characteristics of All Patients
White (n ⫽ 1,874)
Parameter
Median age, years
Median PSA, ng/mL
PSA
⬍ 4 ng/mL
4-10 ng/mL
10-20 ng/mL
⬎ 20 ng/mL
No.
African-American (n ⫽ 162)
%
No.
62
7.0
224
1151
356
143
%
P
60
8.8
12.1
61.4
19.0
7.5
13
83
46
20
8.0
51.2
28.4
12.4
.002
Gleason grade
2-6
7
8-10
1384
376
114
73.8
20.1
6.1
108
33
21
66.6
20.4
13.0
.003
Stage*
T1c
T2a
T2b
T2c
866
632
208
168
46.2
33.7
11.1
9.0
57
66
14
25
35.2
40.8
8.6
15.4
.004
Percentage of positive biopsy specimens
ⱕ 50%
⬎ 50%
1462
412
78.0
22.0
115
47
71.0
29.0
.040
*1992 AJCC clinical staging system.
adjuvant therapy given after local therapy and a lack of
consistent definition of the risk groups. In this analysis,
patients with clinically localized prostate cancer from the
Hospital of University of Pennsylvania (HUP), Philadelphia, PA, and Brigham and Women’s Hospital (BWH),
Boston, MA, treated with RP and no adjuvant therapy
formed the study cohort. PSA outcome for African-American and white men were compared using a previously
established risk group stratification based on the PSA,
Gleason score, clinical T stage, and percentage of positive
biopsy specimens.36,37
PATIENTS AND METHODS
Patient Population
Between 1989 and 2000, 2,036 men were treated with RP for PSA
detected or clinically palpable localized prostate cancer at the BWH
and the HUP. Patients who received neoadjuvant androgen-suppression
therapy, adjuvant radiation, or both were excluded. One hundred
sixty-two African-American men and 1,874 white men were included
in this study. Table 1 lists the preoperative clinical characteristics of the
entire study cohort.
Preoperative Staging
In all cases, staging evaluation included a history and physical
examination, including a digital rectal examination (DRE), serum PSA,
computed tomography scan of the pelvis or an endorectal and pelvic
coil magnetic resonance imaging scan of the prostate and pelvis, bone
scan, and a transrectal ultrasound-guided needle biopsy of the prostate
with Gleason score histologic grading.38 Whereas during the study
period, bone scans, magnetic resonance imaging, or computed tomography scans were obtained routinely, on this day they would only be
obtained in patients with high-risk disease. A sextant biopsy was
performed using an 18-gauge Tru-Cut needle (Travenol Laboratories,
Deerfield, IL). Sextant biopsy specimens were obtained in the majority
of RP-managed patients at HUP (56%) and BWH (75%). The remaining 44% of patients at HUP had fewer than six (18% of patients) or
more than six (26% of patients) biopsy specimens. The clinical stage
was obtained from the DRE findings using the 1992 American Joint
Committee on Cancer (AJCC) staging system.39 Radiologic and biopsy
information was not used to determine clinical stage. The PSA level
was obtained on an ambulatory basis before radiologic studies and the
biopsy procedure. All pretreatment PSA values were obtained within 1
month of the date of the surgery. PSA measurements40 were made
using the Hybritech (Beckman Coulter Inc, Fullerton, CA), Tosoh
(Tosoh Inc, San Francisco, CA), or Abbott (Abbott Laboratories,
Abbott Park, IL) assays.
Treatment and Histopathologic Assessment
A referee genitourinary pathologist reviewed the diagnostic biopsy
specimens for all patients undergoing surgery at the HUP (J.E.T.) or
BWH (A.A.R.). Surgical treatment consisted of a retropubic RP and
bilateral pelvic lymph node sampling. If the intraoperative frozen
sections of any sampled lymph node were positive for carcinoma, then
RP was aborted. Evidence of extracapsular extension, positive margin,
and seminal vesicle invasion were noted and recorded.
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2865
IMPACT OF RACE ON PSA OUTCOME
Table 2.
Pretreatment Characteristics of Low- and High-Risk Patients
Low-Risk Patients
White (63%)
(n ⫽ 1,177)
Parameters
No.
PSA
⬍ 4 ng/mL
4-10 ng/
mL
10-20 ng/
mL
⬎ 20 ng/
mL
High-Risk Patients
African-American
(45%) (n ⫽ 73)
%
No.
%
182
897
15.5
76.2
10
59
98
8.3
4
White (37%)
(n ⫽ 697)
P
African-American
(55%) (n ⫽ 89)
No.
%
No.
%
13.7
80.8
42
254
5.7
36.4
3
24
3.4
27.0
5.5
258
37.4
42
47.2
143
20.5
20
22.4
.59
Gleason score
2-6
7
8-10
1032
145
87.6
12.4
68
5
93.2
6.8
.15
352
231
114
50.5
33.1
16.4
40
28
21
45
31.5
23.5
.16
Stage*
T1c
T2a
T2b
T2c
672
439
66
57.1
37.3
5.6
36
36
1
49.3
49.3
1.4
P
.23
194
193
142
168
27.8
27.7
20.4
24.1
21
30
13
25
24
33.7
14.6
27.7
.06
.34
*1992 AJCC clinical staging system.
Follow-Up
The median follow-up duration for the entire cohort was 42 months
(range, 6 to 132 months). The patients were examined 1 month after
surgery and then at 3-month intervals for 2 years, every 6 months for
5 years, and annually thereafter. At each follow-up appointment, the
serum PSA level was measured before the DRE was performed. No
patients were lost to follow-up.
Statistical Analysis
PSA failure was defined as two detectable (⬎ 0.2 ng/mL) PSA
values obtained after an undetectable measurement. The time of PSA
failure was taken as the time of the first detectable PSA. Time zero was
the date of RP. If a PSA never became undetectable after surgery, then
PSA failure was considered to have occurred at time equal to zero. PSA
outcome was defined as PSA failure-free survival at 5 years, which was
estimated using the actuarial method of Kaplan and Meier41 and
graphically displayed.
Three risk groups were defined36,37 based on the pretreatment PSA
level, biopsy Gleason score, and 1992 AJCC T stage. Low-risk patients
had a preoperative PSA level of ⱕ 10 ng/mL, a biopsy Gleason score
of ⱕ 6, and 1992 AJCC clinical stage T1c or T2a disease. High-risk
patients had a PSA level of greater than 20 ng/mL, a biopsy Gleason
score of ⱖ 8, or 1992 AJCC clinical stage T2c disease. The remaining
patients with ⱕ 50% or more than 50% positive biopsy specimens were
classified as low- and high-risk, respectively, based on a previous study
showing the importance of the percentage of positive biopsy specimens
in intermediate-risk patients. PSA outcome was reported for the lowand high-risk groups. Specifically, using a log-rank test,42 PSA outcome was compared in low- and high-risk groups stratified by race.
RESULTS
Pretreatment Clinical Characteristics
The median age for white and African-American men
was 62 and 60 years, respectively, and the median PSA
level was 7.0 and 8.8 ng/mL, respectively (Table 1). The
pretreatment clinical factors for all patients revealed more
advanced disease in the African-American cohort (Table 1).
African-American men had a statistically significant increase in PSA (P ⫽ .002), Gleason score (P ⫽ .003),
clinical T stage (P ⫽ .004), and percentage of positive
biopsy specimens (P ⫽ .04). Also, 55% of the AfricanAmerican patients were in the high-risk group versus 37%
of the white patients. However, there was no statistical
difference in the distribution of PSA, clinical T stage, or
Gleason score between racial groups within each of the lowand high-risk groups as summarized in Table 2.
PSA Failure-Free Survival
The median follow-up for African-American and white
patients in the low- and high-risk groups was not statistically different. Specifically, the median follow-up for African-American and white men in the low-risk groups for
patients censored at the time of PSA failure was 38 and 35
months, respectively. For high-risk groups, it was 22 and 23
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2866
CROSS ET AL
Fig 1. PSA failure-free (bNED) survival by race for low-risk patients (P ⴝ
.70). bNED, biochemical no evidence of disease.
months, respectively. The 5-year estimate of PSA outcome
was 87% in the low-risk group for both African-American
and white patients (P ⫽ .70) and 28% versus 32% in
African-American and white patients, respectively, in the
high-risk group (P ⫽ .28). These results are illustrated in
Figs 1 and 2.
DISCUSSION
Previous studies have attempted to compare PSA outcome stratified by race after RP for early-stage prostate
cancer. These studies are listed in Table 3. Four of the six
studies revealed that race was not a significant predictor of
PSA failure.6-11 These studies are limited because they fail
to stratify patients for known clinical predictors of PSA
failure. Previously published studies confirm that the pretreatment PSA level, 1992 AJCC clinical T stage, and
biopsy Gleason score are independent predictors of PSA
failure-free survival after RP43-45 or external-beam radiation
therapy.44 Therefore, when comparing PSA outcome, it is
Table 3.
Fig 2. PSA failure-free (bNED) survival by race for high-risk patients (P ⴝ
.28). bNED, biochrmical no evidence of disease.
important to control for these factors. Two studies reported
on PSA outcome between African-American and white
patients with localized prostate cancer by risk groups based
on PSA, clinical T stage, and Gleason score.34,35 Both of
these studies included patients that had received neoadjuvant or adjuvant hormonal therapy or adjuvant radiation. In
addition, whereas low-risk was defined consistently in these
studies, intermediate- and high-risk definitions differed.
The current study compared PSA outcome among racial
groups after RP for localized prostate cancer stratified by
pretreatment clinical factors into established risk groups and
in the absence of adjuvant or neoadjuvant therapies. The
main finding of this study was that PSA outcomes between
racial groups were not significantly different for the lowand high-risk groups (P ⫽ .70 and P ⫽ .28, respectively).
However, at presentation, the PSA, clinical T stage, Gleason
score, and percentage of positive biopsy specimens for
African-American men were significantly more advanced
Studies Evaluating the Association of Race and Recurrence After RP for Clinically Localized Prostate Cancer
Study
Study Population/Years
African-American
White
Statistical Significance for
Racial Differences
in Recurrence, (P)
Moul et al, 19966
Iselin et al, 19987
Eastham et al, 20008
Powell et al, 20009
Freedland et al, 200010
Tarman et al, 200011
Cross et al, current study
Walter Reed Army Med Center/1975-1995
Duke University Med Center/1970-1996
LSU Veterans Affairs Med Center/1990-1998
Wayne State University Harper Hospital/1991-1995
UCLA Veterans Affairs Med Center/1991-1999
Multiple Institutions of the Defense Department/1987-1997
Brigham Women’s and University of PA Hospitals/1989-2000
107
115
218
100
125
192
162
366
1,204
257
178
148
866
1,874
Significant, .049
Not significant, .14
Not significant, .97
Not significant, .42
Not significant, .20
Significant, .035
Not significant*
Ethnic Composition
*Low-risk group P, .70 and high-risk group P, .28.
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2867
IMPACT OF RACE ON PSA OUTCOME
compared with white men. As a result, African-American
men presented with more advanced disease and at younger
ages, as noted by a higher proportion of African-American
men compared with white men in the high-risk group (55%
v 37%, respectively) and lower proportion of AfricanAmerican men compared with white men in the low-risk
group (45% v 63%, respectively).
This study has limitations. First, the follow-up period
may not have been long enough to see a statistical difference in PSA outcome in the low-risk group because failure
can be protracted. Second, retrospective studies are not
conclusive because of the possibility of unknown confounding factors that can impact results. Third, given the numerical difference, although not statistically significant in PSA
outcome for high-risk patients stratified by race as shown in
Fig 2, there is the possibility that a difference may emerge
with a larger cohort of African-American men and longer
follow-up.
Despite the worse mortality rate for African-American
men with prostate cancer compared with white men, this
study and four others7-10 did not find race to be a significant
predictor of recurrence after RP. However, African-American men with prostate cancer present at a younger age and
with more advanced disease. Given that PSA outcome is not
significantly different and more favorable for low-risk
African-American and white individuals at 5 years, this
article provides evidence to support prostate cancer screening in African-American men at a younger age.
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