Open Journal of Urology, 2013, 3, 200-205 Published Online September 2013 (
The Use of PCA3 Can Reduce the Number of Prostate
Biopsies Performed in a Community-Based Urologic
Bradley M. Boelkins1, Christopher M. Whelan1,2, Richard J. Kahnoski1,2,
Jonathan Todd Bolthouse1,2, Brian R. Lane1,2*
1Michigan State University, East Lansing, USA
2Spectrum Health Hospital System, Grand Rapids, USA
Email: *
Received April 28, 2013; revised May 26, 2013; accepted June 2, 2013
Copyright © 2013 Bradley M. Boelkins et al. This is an open access article distributed under the Creative Commons Attribution Li-
cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Purpose: It is now generally accepted that PSA screening identifies many prostate cancers that are low-risk and may
not need treatment. PCA3 is a prostate cancer-specific marker with improved diagnostic accuracy when compared with
PSA in research studies. It remains unknown whether PCA3 testing can reduce the unnecessary diagnosis and treatment
of prostate cancer in routine practice. We evaluated whether the use of PCA3 in clinical practice decreases the number
of biopsies being performed in response to PSA testing. Methods: 64 consecutive patients undergoing PCA3 measure-
ment in a single community-based urology practice were analyzed for rates of biopsy performance and prostate cancer
detection. Results: Median PSA was 5.0 (range: 0.4 - 38.6) and 50% had undergone prior biopsy without evidence of
cancer. Median PCA3 score was 13.6 (range: 1.6 - 133.0) with 14 patients having an elevated PCA3 (>35). Prostate
biopsy was avoided in 50 of 64 patients (78%). Of the 11 patients undergoing biopsy for abnormal PCA3, 7 had pros-
tate cancer (64%). At >2-year median follow-up, 39 of the remaining 50 patients (78%) avoided subsequent biopsy.
Only 5 prostate cancers were diagnosed during follow-up. Conclusions: When used in routine clinical practice, PCA3
appears to reduce the number of biopsies being performed in response to elevated PSA. Given the increasing interest in
strategies to reduce unnecessary prostate cancer diagnosis and treatment, this FDA-approved and widely-available mo-
lecular test appears to achieve these goals. Further testing will clarify the role of PCA3 in initial and subsequent prostate
cancer screening paradigms.
Keywords: Prostate Cancer; Prostate Cancer Antigen 3 (PCA3); Prostate Biopsy
1. Introduction
Current controversy over PSA screening has arisen from
an associated increase in both prostate cancer diagnosis
and treatment. The latest United States Preventive Ser-
vices Task Force (USPSTF) Recommendation Statement
has specifically cited the following concerns: lack of di-
rect effect on prostate-cancer specific mortality or overall
mortality, the harms of potentially-unnecessary diagnos-
tic procedures (prostate biopsy, PB), and the harms of
potentially-unnecessary treatment [1]. Among men with
PSA levels > 4 ng/mL who undergo 10 - 14 core PB,
60% - 73% are found not to have cancer on pathologic
examination [2-4]. The procedure can cause discomfort
and complications, including urosepsis, acute urinary re-
tention, and hematuria, and the probability of having a
positive biopsy decreases with each subsequent biopsy
[5,6]. These difficulties have motivated development of
new and more specific screening tests for prostate cancer
to decrease the number of unnecessary PBs.
The PCA3 gene, which is highly over-expressed in
prostatic cancer cells, has been found to be more specific
for prostate cancer detection than PSA [7-9]. Goode et al.
demonstrated that PCA3 had a specificity of 79% com-
pared to 47% for PSA for cancer detection at initial bi-
opsy [10]. At repeat biopsy, this disparity in specificity
increased to 70% vs 27% [10]. PCA3 may therefore find
a role in patients prior to initial biopsy and in those who
may be considered for repeat biopsy. We hypothesized
that urinary PCA3 testing may serve to decrease the
number of unnecessary PBs performed in these patients.
*Corresponding author.
opyright © 2013 SciRes. OJU
Table 1. Clinical information regarding 64 patients evalu-
ated with PCA3*.
In the present study, we analyzed the utility of PCA3
testing in reducing PB in a community-based urologic
2. Materials and Methods
All patients referred for abnormal PSA and/or digital
rectal examination (DRE) were educated regarding the
risks and benefits of PSA screening and options for sub-
sequent evaluation. Patients were offered immediate PB
if it was felt that their current risk of PC, and high-grade
PC in particular, warranted this intervention [11]. For
patients with a lesser current risk of high-grade PC, dis-
cussion included risks and benefits of urinary PCA3
testing to clarify the current risk of prostate cancer. Pa-
tients electing to undergo PCA3 testing gave a post-
digital exam urine sample, which was adequate for
analysis in >96% of cases (Bostwick Laboratories, Rich-
mond, VA; Dianon Systems, Shelton, CT) [12]. The
PCA3 value is defined as the ratio of PCA3 mRNA to
PSA mRNA multiplied by 1000. PB was recommended
to patients with abnormal PCA3 and not recommended in
patients with normal PCA3. For the purposes of our
study, abnormal PCA3 was defined a priori as 35, ac-
cording to the manufacturer’s instructions. Subsequent
prostate cancer screening was performed with annual
rectal exam and periodic PSA testing. For patients with
elevated future risk of PC, discussion included risks and
benefits of prostate cancer chemoprevention [11]. Men
with benign prostatic enlargement and/or lower urinary
tract symptoms were advised to consider the use of 5α-
reductase inhibitors (5ARI’s).
IRB approval (IRB#2012-148) was obtained for eva-
luation of the medical records of all patients in whom
urinary PCA3 testing was obtained. Those with a prior
history of prostate cancer were excluded and the initial
PCA3 test was used as the referent for those with multi-
ple tests. Between October 2009 and June 2012, 64 total
patients met inclusion criteria. Data were maintained in a
HIPAA-compliant database, which included information
pertaining to the decision to perform PCA3 testing and
subsequent urologic follow-up in each patient. For statis-
tical comparisons, the level of significance was defined
as p < 0.05.
3. Results
Median patient age,
yrs (IQR) 64 (58 - 71)
Percentage of
Caucasians (No.) 95% (61)
Percentage of
African-Americans (No.) 5% (3)
Median PSA, ng/ml (IQR) 5.0 (3.7 - 6.6)
Percentage with
abnormal DRE (No.) 13% (8)
Median prostate size,
gm (IQR) 38 (30 - 50)
Percentage with prior
medical therapy for BPH (No.)27% (17)
Percentage undergoing prior
prostate biopsy (No.) 50% (32)
Number of prior
biopsies (No.)
1: 13
2: 10
3: 2
4: 5
5: 1
9: 1
Median AUA-SS (IQR) 7 (3 - 10)
Median PCA3, (IQR) 13.6 (5.9 - 32.9)
Percentage of abnormal
PCA3 (>35) (No.) 22% (14)
*Two patients had a non-informative PCA3.
Median estimated prostate size on DRE was 38 grams
(IQR: 30 - 50). A positive correlation was found between
PSA level and prostate volume (r2 = 0.202, p = 0.0001).
No correlation was demonstrated between PCA3 and PSA
levels (r2 = 0.0039, p = 0.31) or between PCA3 level and
prostate volume (r2 = 0.0007, p = 0.42). PSA, DRE and
biopsy results in patients with normal and abnormal PCA3
values are indicated in Tabl e 2.
An initial decision for prostate biopsy was made in only
22% (n = 14) of men undergoing PCA3 testing, including
11 with abnormal PCA3 values. Three patients with ab-
normal PCA3 values have not undergone initial biopsy
despite this finding. Two of these patients refused biopsy
and one elected for active surveillance due to age and
multiple prior negative biopsies. Three additional patients
elected PB in the absence of an abnormal PCA3, including
two with inadequate PCA3 results and one with ongoing
concern about the risk of PC despite normal PCA3. Initial
biopsy was therefore not performed in 78% of patients (n
= 50). Median PCA3 for patients undergoing or not un-
dergoing PB was 52.2 (IQR: 44.6 - 63.8) vs 8.5 (IQR: 5.3
- 20.6), respectively (p < 0.001). Median PCA3 for pa-
tients with or without cancer at PB was 55 (IQR: 51 - 88)
an 44 (IQR: 43 - 48), respectively (p = 0.15).
Characteristics of the study population are found in Table
1. Sixty-two of 64 samples were adequate for PCA3 test-
ing (96.9%). Median PCA3 was 13.6 (IQR: 5.9 - 32.9),
with 22% abnormal (>35). Median PSA value was 5.0
ng/ml (IQR: 3.7 - 6.6) and 13% had an abnormal DRE.
50% of men had undergone prior PB, with 13, 10, and 9
men undergoing 1, 2, and 3 or more prior PB, respectively. d
Copyright © 2013 SciRes. OJU
Copyright © 2013 SciRes. OJU
Table 2. Initial PB results according to PCA3.
Abnormal PCA3 (n = 14) Normal PCA3 (n = 50)
Median PSA, ng/ml (IQR) 5.1 (4.4 - 6.2) 5.0 (3.6 - 7.4)
Percentage with abnormal DRE (No.) 0% (0) 16% (8)
Proportion in whom PB recommended (No.)
Proportion in whom PB performed (No.)
100% (14)
79% (11)
0% (0)
6% (3)
Proportion with PC (No.)
Gleason 6
Gleason 7
Gleason 8 or higher
Proportion with primary Gleason pattern 4 or 5 (No.)
Proportion with clinically-insignificant PC* (No.)
50% (7)
14% (2)
14% (2)
2% (1)
0% (0)
0% (0)
Median number of cores involved (range) 3 (1 - 12) 3
Treatment Modality
Robotic prostatectomy
*Clinically-insignificant PC defined as Gleason score no higher than 6, 1 - 2 cores positive, 50% or less cancer in any involved core, and PSA density < 0.15 [13].
In patients with abnormal PCA3, cancer was detected
at initial PB in 7 patients, which represents 64% of PB
performed for abnormal PCA3 and 50% of patients with
abnormal PCA3 overall (Table 2). Predominant Gleason
pattern 4 was present in 2 patients (Gleason 4 + 3 and 4 +
5), with Gleason 3 + 3 in the remaining 5 patients, in-
cluding 2 clinically-insignificant cancers (Gleason 3 + 3
in <50% of 1 - 2 cores and PSA density < 0.15) [13].
Initial active treatment was pursued in 4 patients and
surveillance in 3 patients. Cancer was detected at initial
PB in 1 of 3 patients with normal PCA3 values. This
patient elected brachytherapy for Gleason 3 + 4 cancer
detected in 3 of 13 cores.
With median 25 month follow-up (IQR: 14 - 29 mon-
ths) after PCA3 testing, 81% of those with normal PCA3
have undergone follow-up DRE and 72% have under-
gone subsequent PSA testing. The median follow-up
PSA value was 4.3 (IQR: 2.0 - 6.4). The median decrease
in PSA in patients taking or not taking 5α-reductase in-
hibitors was 25% (IQR: 0% - 52%) vs 0% (IQR: 4% -
6%), respectively (p = 0.005). Two patients died in fol-
low-up, both from non-prostate cancer-related issues.
78% of patients (n = 39) have not undergone subsequent
biopsy (Table 3). Indications for PB during follow-up
included rising PSA (n = 9), new prostate nodule on DRE
(n = 1), and abnormal repeat PCA3 (n = 1). PC was de-
tected in 45% of these 11 patients (n = 5), each having a
predominant Gleason pattern of 3. PC detected in fol-
low-up included 2 clinically-insignificant cancers accord-
ing to Epstein criteria [13]. Treatment selection included
active surveillance (n = 3) and robotic prostatectomy (n =
Table 3. Follow-up information at 25 months after initial
normal PCA3 screening (n = 50).
Proportion in whom PB was recommended (No.) 22% (11)
Indication for follow-up biopsy
Rising PSA
New prostate nodule
Abnormal PCA3 at repeat testing
Proportion with PC
Gleason 6
Gleason 7
Gleason 8 or higher
Proportion with primary Gleason
pattern 4 or 5 (No.)
Proportion with clinically-insignificant PC* (No.)
10% (5)
0% (0)
40% (2)
Median number of cores involved (range) 2 (2 - 9)
Treatment Modality
Robotic prostatectomy
*Clinically-insignificant PC defined as Gleason score no higher than 6, 1 - 2
cores positive, 50% or less cancer in any involved core, and PSA density
<0.15 [13].
4. Discussion
The weaknesses of PSA as a screening tool for prostate
cancer are under intensifying scrutiny within the chang-
ing landscape of prostate cancer diagnosis and treatment.
[1] PSA, a prostate tissue specific (rather than prostate
cancer specific) assay, was first approved by the Food
and Drug Administration (FDA) in 1986 for prostate
cancer surveillance and in 1994 as a screening tool in
asymptomatic men [14-16]. During the last two decades,
widespread PSA testing in the United States has greatly
increased the incidence of PC as more men are subjected
to prostate biopsy. Indeed, three fourths of US men 50
years of age and older underwent a PSA test [17]. The
poor specificity and sensitivity of PSA have been out-
lined in multiple studies, including the Prostate Cancer
Prevention Trial [17,18]. PSA threshold values of 1.1,
2.1, 3.1, and 4.1 ng/mL yielded sensitivities of 83.4%,
52.6%, 32.2%, and 20.5% and specificities of 38.9%,
72.5%, 86.7% and 93.8% respectively [18]. The authors
concluded that there is no threshold PSA with both ade-
quate sensitivity and specificity for healthy men [18].
This clouds the decision-making process for the patient,
primary care physician and urologist in the interpretation
of PSA values.
Even so, over 1 million prostate biopsies are per-
formed annually among Medicare beneficiaries, largely
in response to screening with PSA [19]. Recently, Loeb
and associates published data on a cohort of 17,472 men
from the SEER-Medicare database that underwent pros-
tate biopsy [19]. The authors found that prostate cancer
was diagnosed in only 17% of men. In addition, 6.9% of
men were hospitalized within 30 days of biopsy, more
than twice the proportion in a control population [19].
While often viewed as a routine office procedure, pros-
tate biopsy offers a real risk of bleeding and infection in
patients with an elevated PSA, the majority of who do
not have prostate cancer.
The problems with PSA as a screening test have been
emphasized by the US Preventative Services Task Force
and the American Academy of Family Physicians who
recommend against routine PSA screening to detect pro-
state cancer in asymptomatic men [1]. While this remains
the subject of intense debate within the medical commu-
nity, most would agree the development of a more accu-
rate screening tool for prostate cancer is critical.
Discovered in 1999, PCA3 is a prostate specific gene
that is over expressed in 95% of prostate cancer cells, at
levels that are a median 66-fold higher than adjacent non-
cancerous prostate cells [7-9]. A commercially-available
PCA3 assay has been approved as an adjunct to PSA
testing in men with a suspicion of prostate cancer. Unlike
PSA, PCA3 is not significantly influenced by age, in-
flammation, the use of 5-alpha reductase inhibitors or
BPH. Gaining ground in academic institutions, PCA3 has
been shown to have improved specificity as compared to
PSA alone. A large multicenter trial recently evaluated
the diagnostic performance of PCA3 to detect PC in men
with increased PSA. Men underwent both PSA and
PCA3 testing prior to planned PB in response to increa-
sed PSA (2.5 ng/ml or greater) and/or abnormal DRE.
The vast majority of urine samples (97.5%) were ade-
quate for PCA3 testing and 33.4% of these yielded a
PCA3 score > 35 [20]. Using this cutpoint for PCA3, the
number of false-positives (unnecessary biopsies) was
reduced by 77%. Crawford and colleagues concluded
that “urinary PCA3 testing in conjunction with PSA has
the potential to significantly decrease the number of un-
necessary prostate biopsies” [20].
Herein, we describe the actual impact of urinary PCA3
testing on the number of PBs performed in a community-
based urology practice. We report on a series of patients
in whom PCA3 was measured in lieu of a decision for
immediate PB based on PSA alone. We found that PB
was avoided in 78% of patients that underwent initial
PCA3 testing, almost identical to that predicted by Craw-
ford et al. [20]. In addition, at a median follow-up of 25
months, PB was avoided in 78% of men who were fol-
lowed after a normal PCA3 value. In men who under-
went PB for an abnormal PCA3, prostate cancer was
detected in 64%, similar to the 61% PC detection rate in
the prior study [20]. No patient with PCA3 score < 35
was found to have a predominant Gleason pattern 4/5
cancer, while 18% of patients undergoing PB for abnor-
mal PCA3 had a predominant Gleason pattern 4.
This study has several limitations, including the ab-
sence of pathologic confirmation of the absence of PC in
patients electing not to undergo PB, leaving the false
negative rate unknown. While this limitation was absent
from other research studies that have compared the per-
formance of PCA3 with PSA and other parameters for
prediction of PC at PB in men who have already made a
decision for PB, the design of those studies prevents an
analysis of the impact of PCA3 testing on the decision to
pursue PB. While the diagnostic performance of PCA3
has by now been well-categorized, the clinical impact of
PCA3 score has not been evaluated. The purpose of our
study was to determine the actual impact that introduc-
tion of PCA3 may have upon clinical practice; our results
indicate a reduction in the number of PB performed,
supporting our hypothesis. Another limitation of the
study is a smaller sample size, which was impacted by
lack of coverage for PCA3 testing in many patients who
otherwise would have undergone testing. These and other
selection biases may limit the generalizability of our
findings, and a future direction of this research is to col-
laborate with other sites to further assess the generaliza-
bility of our findings.
The current study indicates that PCA3 testing can sig-
nificantly reduce the number of biopsies performed in
response to elevated PSA within a community-based uro-
logic practice. If more community practices adopt this
approach, these improvements may be realized on a lar-
ger scale. This may ultimately reduce the morbidity as-
sociated with the overuse of prostate biopsy. A strategy
that leads to the performance of fewer prostate biopsies
with an improved PC detection rate when performed will
Copyright © 2013 SciRes. OJU
greatly improve the quality of PC care within the com-
munity. Previous studies have shown the sensitivity of
PCA3 score to be lower than PSA testing, indicating that
PCA3 should not replace PSA as a screening tool [10,12,
16,17]. Instead, given its superior specificity, PCA3
score could be used to stratify men with elevated PSA
based on risk of PC. The addition of PCA3 score to PSA
and other clinical parameters within a nomogram pre-
dicting PC and high-grade PC has been proposed and
warrants further validation [21].
5. Conclusion
Measurement of PCA3 score in a community-based uro-
logic practice successfully reduced the number of pros-
tate biopsies performed in response to PSA testing by
78%. At a median of >2 year follow-up of these patients,
78% of these men also avoided subsequent biopsy. Con-
versely, PC was detected in 64% of men undergoing PB
for a PCA3 score > 35. Measurement of PCA3 score in
lieu of PB for men with elevated PSA has the potential to
reduce unnecessary prostate cancer diagnosis and treat-
ment if used more widely.
6. Acknowledgements
The authors would like to thank Kevin Hinton, Bonnie
Dykstra and Maureen Gebben for assistance with re-
search activities.
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