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The Prostate 31:139–141 (1997)
Prostate Cancer In African-American Men
The recent New England Journal of Medicine article by
Morgan et al. [1] raises several questions about the
need for improved prostate cancer (PCa) control in
African American men (AAM). AAM have up to two
times the incidence and three times the death rate
from prostate cancer of Caucasian men (CM) [2]. PCa
in AAM also appears to occur at younger ages. AAM
have thus been designated as a distinct high-risk
group and advised to have their annual cancer related
check-up beginning at age 40, rather than age 50 as for
the general population [3]. From radical prostatectomy series, AAM have also been noted to have higher
mean tumor volumes with higher PSA levels [4]. The
recent article by Morgan et al. focused primarily on
the statistical manipulation of PSA values in an attempt to improve PSA diagnosis through age-specific
reference ranges for AAM without sufficient consideration of the ultimate endpoint in early detection,
namely, the reduction of disproportionate mortality.
Age-specific reference ranges were initially developed by Oesterling et al. [5] to account for increasing
average PSA by age groups, predominantly related to
greater probability of gland enlargement from benign
prostatic hyperplasia (BPH) and resultant greater PSA
false positives. The purported benefit of age-specific
reference ranges would be to allow greater detection
sensitivity for younger men while increasing the
specificity of PSA for older men. The initial agespecific PSA reference ranges [5] (Table I) were thus
derived from only CM.
Participation of AAM in early-detection projects has
always been disproportionately low, with the greatest
accrual rate of 7% attained in the American Cancer Society-National Prostate Cancer Detection Project (ACSNPCDP) [6]. Without consideration of the significantly
greater PCa incidence among AAM, focusing only on
PSA sensitivity and specificity [1] may negate the greater
mortality impact of cancers that might also be more aggressive. AAM have been noted to have 1.5 times the
mortality rate when controlling for stage [7] in the Surveillance Epidemiology and End Results (SEER) cancer
registry from the metropolitan Detroit area.
A major difficulty in constructing age-specific reference ranges for AAM can be seen in the entire shift
of focus by Morgan et al. [1] to produce 95% sensitivity vs. the original goal of 95% specificity in Oester© 1997 Wiley-Liss, Inc.
ling’s original derivation of age-specific reference
ranges [5] (Table I). Herein lies the statistical difference between PSA levels of AAM and CM when using
the 95th percentile (i.e., mean PSA + 2 standard deviations) for patients without evidence of cancer.
AAM and CM had nearly identical median PSA levels
when controlling for age, but AAM had greater PSA
variability with increasing age (i.e., larger standard
deviations), producing markedly higher 95th percentiles for normal screening patients [1]. These significantly higher age-specific reference ranges (95th percentiles) for AAM resulted in 41% of prostate cancer
cases in AAM being missed vs. only 15–20% of cancers
missed among CM. Therefore, the authors chose to
emphasize the 95th percentile for cancer detection
from their clinical cohort and obtained age-specific
reference ranges nearly identical to the original values
obtained by Oesterling [5] for CM with benign prostates. Interestingly, they did not emphasize that the
same concept of 95th percentile cancer detection obliterates age-specific PSA ranges for CM over age 50
(Table I). Again, the inversion of emphasis from high
specificity to high sensitivity will doubtless confuse
many clinicians. Perhaps few will grasp the marked
differences in early detection when age-specific reference ranges for AAM emphasize 95th percentile sensitivity and have nearly identical values for CM emphasizing 95 percentile specificity. Should we therefore
call it age-sensitive reference ranges for AAM?
TABLE I. Age-Specific Reference Ranges: Specificityand Sensitivity-Driven Differences*
Specificity driven
Sensitivity (95th percentile)
et al. [5]
et al. [1]
et al. [1]
et al. [1]
*Note the similar PSA decision levels (boldface columns) for Caucasian men (CM) emphasizing specificity and those for AfricanAmerican men (AAM), relying on sensitivity. The sensitivitydriven column for CM also remains constant above age 50.
Fig. 1. Tumors having similar total volume and Gleason score could produce greater numbers of biopsies with individual Gleason scores
$7 if the volume of the grade 4 component is larger in AAM.
Perhaps the more interesting parameter for early
detection outcomes is a test’s positive predictive value
(i.e., PPV = true positives/[true positives + false positives]), insofar as this also reflects the incidence of the
disease. Deriving the PPV for the early detection cohort in the Morgan et al. [1] study shows up to 50%
higher PPV for AAM. We have also noted a similar
pattern of significantly higher PPV for AAM in our
large biopsy series (8), regardless of the PSA value or
other diagnostic criteria. Significantly higher PPV for
AAM therefore offers more insight into early detection, having greater cancer yield with lower false positives and lower screening costs among AAM. We have
presented data [8] showing that screening costs for
AAM will always be 25–50% less expensive than
early-detection approaches for CM depending on the
decision levels of PSA. Our large biopsy series suggests that the higher incidence of prostate cancer
among AAM could have even greater mortality implications when we consider the types of cancers detected compared to the case with CM.
The greater incidence of prostate cancer among
AAM does not fully account for their disproportionate
mortality when controlling for stage and suggests that
prostate cancers in AAM have greater biologic potential. Delay in diagnosis, or lack of access to appropriate therapeutic options owing to socioeconomic factors, does not appear adequate to explain the 1.5 times
greater mortality rate for AAM given similar-stage
prostate cancer [7]. Analogous to greater tumor vol-
umes identified among AAM when controlling for
PSA level [4], we have also noted significantly greater
numbers of biopsy cores involved with cancer in AAM
(P < 0.001) when a targeted sextant biopsy technique is
utilized [9]. The targeted sextant biopsy technique involves directing a biopsy within each sextant to the
dominant region of suspicion as defined by hypoechoic change or foci of distinct increased color
doppler flow. From comparison with our radical prostatectomy specimens, this leads to a more accurate
representation of Gleason score with the eventual
radical prostatectomy specimen [10]. More importantly, significantly greater numbers of cancer cores
among AAM had Gleason scores $7 (P < 0.001) and
were distributed in a significantly greater multisextant
pattern than with CM. In other words, the greater
numbers of cancer cores seen among AAM appear to
be related to more diffusion or greater volume of
higher grade cancer among AAM (Littrup, unpublished data).
The concept of the relative distribution of a grade
$4 component has been proposed by McNeil [11] as a
potent predictor of prostate cancer progression. Although the total volume of potentially curable prostate
cancer has been estimated at 3–5 cc, the critical tumor
mass for developing lymph node metastases has been
estimated at 3.2 cc of grade $4 component within a
cancer [11]. Our biopsy data are being finalized for
publication and suggest that the greater numbers of
higher grade cancer seen on biopsy could account for
the disproportionate mortality among AAM. We
therefore proposed the grade-volume hypothesis of
greater volumes of higher grade tumor in AAM (Fig.
1) to emphasize potential differences in not only incidence but also the types of cancers detected among
AAM. Early detection for AAM utilizing any appropriate initiation point of PSA for subsequent follow-up
or biopsy would detect greater numbers of clinically
significant prostate cancers among AAM. The greater
incidence of prostate cancer in AAM would thus
translate into lower relative screening costs, and the
greater biologic potential from tumor grade differences offers even greater potential mortality reductions from early detection.
Lower screening costs with greater potential mortality reductions among AAM thus appear far more
relevant and timely issues for prostate cancer early
detection than focusing on potentially confusing statistical variations in PSA to derive age-specific, reference value differences. If high-risk groups (i.e., AAM
and men with a family history of PCa) are advised to
begin early detection at earlier ages [3], perhaps more
work is needed in defining lower PSA decision levels
for AAM based on attempts to reduce their disproportionate mortality rate. The focus of early detection
should be the greatest potential mortality reduction
for all men at the lowest human and economic costs.
Conclusive mass screening trial results might not be
accomplished in time for practical application or before their technological obsolescence. We believed that
PSA decision levels of 2 ng/ml for high-risk men and
4 ng/ml for the general population are much simpler
and are only the first step in tailoring individual risk
assessment [9]. Alternatively, we could continue calling multiple PSA ranges age-specific for CM [5] and
change the term to age-sensitive PSA reference ranges
for AAM [1].
Peter J. Littrup, MD
Departments of Radiology, Urology, and
Radiation Oncology
Wayne State University School of Medicine,
Harper Hospital,
Detroit, MI 48201
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