The Use of PCA3 Can Reduce the Number of Prostate Biopsies Performed in a Community-Based Urologic Practice

doi:10.4236/oju.2013.35037

Paper Menu >>

Journal Menu >>

Open Journal of Urology, 2013, 3, 200-205

http://dx.doi.org/10.4236/oju.2013.35037 Published Online September 2013 (http://www.scirp.org/journal/oju)

The Use of PCA3 Can Reduce the Number of Prostate

Biopsies Performed in a Community-Based Urologic

Practice

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: *[email protected]

Received April 28, 2013; revised May 26, 2013; accepted June 2, 2013

cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

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.

B. M. BOELKINS ET AL. 201

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

practice.

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

B. M. BOELKINS ET AL.

202

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)

2% (1)

0% (0)

Median number of cores involved (range) 3 (1 - 12) 3

Treatment Modality

Surveillance

Brachytherapy

Robotic prostatectomy

Androgen-deprivation

*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 =

2).

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

 Surveillance

 Brachytherapy

 Robotic prostatectomy

 Androgen-deprivation

*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

B. M. BOELKINS ET AL. 203

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

B. M. BOELKINS ET AL.

204

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.

REFERENCES

[1] V. A. Moyer, on Behalf of the US Preventive Services

Task Force, “Screening for Prostate Cancer: US Preven-

tive Services Task Force Recommendation Statement,”

Annals of Internal Medicine, Vol. 157, No. 2, 2012, pp.

120-134.

[2] R. J. Babaian, A. Toi, K. Kamoi, P. Troncoso, J. Sweet, R.

Evans, et al., “A Comparative Analysis of Sextant and an

Extended 11-Core Multisite Directed Biopsy Strategy,”

Journal of Urology, Vol. 163, No. 1, 2000, pp. 152-157.

doi:10.1016/S0022-5347(05)67993-1

[3] C. K. Naughton, D. C. Miller, D. E. Mager, D. K. Orn-

stein and W. J. Catalona, “A Prospective Randomized

Trial Comparing 6 versus 12 Prostate Biopsy Cores: Im-

pact on Cancer Detection,” Journal of Urology, Vol. 164,

No. 2, 2000, pp. 388-392.

doi:10.1016/S0022-5347(05)67367-3

[4] J. C. Presti Jr., J. J. Chang, V. Bhargava and K. Shino-

hara, “The Optimal Systematic Prostate Biopsy Scheme

Should Include 8 Rather than 6 Biopsies: Results of a

Prospective Clinical Trial,” Journal of Urology, Vol. 163,

No. 1, 2000, pp. 163-167.

doi:10.1016/S0022-5347(05)67995-5

[5] B. Djavan, V. Ravery, A. Zlotta, P. Dobronski, M. Do-

brovits, M. Fakhari, et al., “Prospective Evaluation of

Prostate Cancer Detected on Biopsies 1, 2, 3 and 4: When

Should We Stop?” Journal of Urology, Vol. 166, No. 5,

2001, pp. 1679-1683.

doi:10.1016/S0022-5347(05)65652-2

[6] G. I. Pinkhasov, Y. K. Lin, R Palmerola, P. Smith, F.

Mahon, M. G. Kaag, et al., “Complications Following

Prostate Needle Biopsy Requiring Hospital Admission or

Emergency Department Visits—Experience from 1000

Consecutive Cases,” BJU International, Vol. 110, No. 3,

2012, pp. 369-374.

doi:10.1111/j.1464-410X.2011.10926.x

[7] M. J. Bussemakers, A. van Bokhoven, G. W. Verhaegh, F.

P. Smit, H. F. Karthaus, J. A. Schalken, et al., “DD3: A

New Prostate-Specific Gene, Highly Overexpressed in

Prostate Cancer,” Cancer Research, Vol. 59, No. 23,

1999, pp. 5975-5979.

[8] J. B. de Kok, G. W. Verhaegh, R. W. Roelofs, D. Hessels,

L. A. Kiemeney, T. W. Aalders, et al., “DD3(PCA3), a

very Sensitive and Specific Marker to Detect Prostate

Tumors,” Cancer Research, Vol. 62, No. 9, 2002, pp.

2695-2698.

[9] D. Hessels, M. P. van Gils, O. van Hooij, S. A. Jannink, J.

A. Witjes, G. W. Verhaegh, et al., “Predictive Value of

PCA3 in Urinary Sediments in Determining Clinico-

Pathological Characteristics of Prostate Cancer,” Prostate,

Vol. 70, No. 1, 2010, pp. 10-16. doi:10.1002/pros.21032

[10] R. R. Goode, S. J. Marshall, M. Duff, E. Chevli and K. K.

Chevli, “Use of PCA3 in Detecting Prostate Cancer in

Initial and Repeat Prostate Biopsy Patients,” Prostate,

Vol. 73, No. 1, 2012, pp. 48-53.

[11] M. J. Roobol, F. H. Schroder, E. D. Crawford, S. J.

Freedland, A. O. Sartor, N. Fleshner, et al., “A Frame-

work for the Identification of Men at Increased Risk for

Prostate Cancer,” Journal of Urology, Vol. 182, No. 5,

2009, pp. 2112-2120. doi:10.1016/j.juro.2009.07.018

[12] J. Groskopf, S. M. Aubin, I. L. Deras, A. Blase, S. Bod-

rug, C. Clark, et al., “APTIMA PCA3 Molecular Urine

Test: Development of a Method to Aid in the Diagnosis

of Prostate Cancer,” Clinical Chemistry, Vol. 52, No. 6,

2006, pp. 1089-1095. doi:10.1373/clinchem.2005.063289

[13] J. I. Epstein, D. W. Chan, L. J. Sokoll, P. C. Walsh, J. L.

Cox, H. Rittenhouse, et al., “Nonpalpable Stage T1c

Prostate Cancer: Prediction of Insignificant Disease Using

Free/Total Prostate Specific Antigen Levels and Needle

Biopsy Findings,” Journal of Urology, Vol. 160, No. 6,

1998, pp. 2407-2411.

[14] M. C. Wang, L. A. Valenzuela, G. P. Murphy and T. M.

Chu, “Purification of a Human Prostate Specific Anti-

gen,” Investigative Urology, Vol. 17, No. 2, 1979, pp.

159-163.

[15] M. Kuriyama, M. C. Wang, C. L. Lee, C. S. Killian, L. D.

Papsidero, H. Inaji, et al., “Multiple Marker Evaluation in

Human Prostate Cancer with the Use of Tissue-Specific

Antigens,” Journal of the National Cancer Institute, Vol.

68, No. 1, 1982, pp. 99-105.

[16] W. H. Cooner, B. R. Mosley, C. L. Rutherford Jr., J. H.

Beard, H. S. Pond, W. J. Terry, et al., “Prostate Cancer

Detection in a Clinical Urological Practice by Ultrasono-

graphy, Digital Rectal Examination and Prostate Specific

Antigen,” Journal of Urology, Vol. 143, No. 6, 1990, pp.

B. M. BOELKINS ET AL.

205

1146-1154.

[17] I. M. Thompson, D. P. Ankerst, C. Chi, M. S. Lucia, P. J.

Goodman, J. J. Crowley, et al., “Operating Characteristics

of Prostate-Specific Antigen in Men with an Initial PSA

Level of 3.0 ng/ml or Lower,” JAMA, Vol. 294, No. 1,

2005, pp. 66-70. doi:10.1001/jama.294.1.66

[18] I. M. Thompson, P. J. Goodman, C. M. Tangen, M. S.

Lucia, G. J. Miller, L. G. Ford, et al., “The Influence of

Finasteride on the Development of Prostate Cancer,” The

New England Journal of Medicine, Vol. 349, No. 3, 2003,

pp. 215-224. doi:10.1056/NEJMoa030660

[19] S. Loeb, H. B. Carter, S. I. Berndt, W. Ricker and E. M.

Schaeffer, “Complications after Prostate Biopsy: Data

from SEER-Medicare,” Journal of Urology, Vol. 186, No.

5, 2011, pp. 1830-1834. doi:10.1016/j.juro.2011.06.057

[20] E. D. Crawford, K. O. Rove, E. J. Trabulsi, J. Qian, K. P.

Drewnowska, J. C. Kaminetsky, et al., “Diagnostic Per-

formance of PCA3 to Detect Prostate Cancer in Men with

Increased Prostate Specific Antigen: A Prospective Study

of 1962 Cases,” Journal of Urology, Vol. 188, No. 5,

2012, pp. 1726-1731. doi:10.1016/j.juro.2012.07.023

[21] A. K. Wu, A. C. Reese, M. R. Cooperberg, N. Sadetsky

and K. Shinohara, “Utility of PCA3 in Patients Undergo-

ing Repeat Biopsy for Prostate Cancer,” Prostate Cancer

and Prostatic Diseases, Vol. 15, No. 1, 2012, pp. 100-

105. doi:10.1038/pcan.2011.52