E U R O P E A N U R O L O G Y 5 6 ( 2 0 0 9 ) 2 1 5 – 2 2 0218

Conflicts of interest: The authors have nothing to disclose.

References

[1] Vrooman OPJ, Witjes JA. Urinary markers in bladder cancer. Eur Urol

2008;53:909–16.

[2] Grossman HB, Messing E, Soloway M, et al. Detection of bladder

cancer using a point-of-care proteomic assay. JAMA 2005;293:

810–6.

[3] Grossfeld GD, Wolf Jr JS, Litwan MS, et al. Asymptomatic microscopic

hematuria in adults: summary of the AUA best practice policy

recommendations. Am Fam Physician 2001;63:1145–54.

[4] van Rhijn BWG. Considerations on the use of urine markers for

bladder cancer. Eur Urol 2008;53:880–1.

[5] van der Aa MNM, Zwarthoff EC, Steyerberg EW, et al. Microsatellite

analysis of voided-urine samples for surveillence of low-grade non-

muscle-invasive urothelial carcinoma: feasibility and clinical

utility in a prospective multicenter study (Cost-Effectiveness of

Follow-Up of Urinary Bladder Cancer Trial [CEFUB]). Eur Urol

2009;55:659–68.

Robert S. Svatek*

Colin P. Dinney

MD Anderson Cancer Center, Urologic Oncology,

1515 Holcombe, Unit 1373, Houston, TX 77030, USA

*Corresponding author.

E-mail address: rssvatek@sbcglobal.net

DOI: 10.1016/j.eururo.2009.04.014

Re: PCA3 Score before Radical Prostatectomy PredictsExtracapsular Extension and Tumor VolumeWhitman EJ, Groskopf J, Ali A, et al.

J Urol 2008;180:1975–8; discussion 1978–9

Expert’s summary:

Whitman et al examined 72 patients before radical prosta-

tectomy. Following digital rectal examination, urine sam-

ples were taken and PCA3 and prostate-specific antigen

(PSA) mRNA were measured. The PCA3–PSA ratio is the

PCA3 score. The scores were correlated with the histologic

result.

The authors found that 71.2% of the patients had cT1c

tumors, and the rest had cT2 tumors. Median PSA was 4.7

ng/ml (range: 1.0–31.6). Gleason score was 3 + 3 for 69.4%

of patients. All prostatectomy specimens were processed

according to a standardized protocol and were assessed by

two experienced genitourinary pathologists. All tumors

were measured in three dimensions, and tumor volume was

estimated. The median test was performed to determine the

association between PCA3 score and pathologic character-

istics of the tumor.

Upgrading of Gleason score occurred in 21 of 72

cases (29.2%) and downgrading occurred in 11 cases

(15.3%) from biopsy to prostatectomy specimens. Simi-

larly, upstaging was found in 29.1% of the cases (20.8%

pT3a, 8.3% pT3b).

With a cut-off PCA3 score of 47, the resulting sensitivity,

specificity, and accuracy to predict extracapsular extension

(ECE) were 57%, 94%, and 83%, respectively, resulting in a

area under the curve (AUC) of 0.732. When combined with

Gleason score and PSA, PCA3 independently predicted ECE

with an AUC of 0.90.

Expert’s comments:

One of the persistent problems in oncology is the lack of

prognostic factors to determine the fate of the individual

patient. With a better understanding of the molecular base

of tumor development and progression, numerous attempts

have been made to overcome this hurdle. DNA and mRNA

changes have been researched intensively to understand

the differences between tumor cells and normal tissue. It

turned out, however, that tumor cells of the same tumor can

show a wide variety of genetic abnormalities, making it

extremely complex to rely on changes of individual genes

or single-digit numbers of gene sets. While first attempts

with this approach often looked promising [1] in terms of

prognostic differentiation, reproduction of the results

turned out to be difficult or impossible. Even with

the advent of multiple gene analysis using micro tissue

arrays and the possibility of developing gene signatures,

only modest progress (eg, with breast cancer) has been

made to determine the prognosis of individual patients

[2].

For prostate cancer, a PCA3 mRNA-based urine test has

recently been added to the diagnostic armamentarium [3].

While its ability to enhance early detection seems only

modest so far, recent evidence suggests that it may be able

to enhance our prognostic assessment of patients with

clinically localized prostate cancer.

ECE has recently been shown to be a significant

prognostic factor for prostate cancer–related mortality

[4]. Moreover, ECE was the most commonly underestimated

adverse feature in patients who were theoretically eligible

for active surveillance [5].

Thus, when combined with standard prognostic factors

in a nomogram or artificial neural network, PCA3 might be

able to enhance our ability to better characterize clinically

localized prostate cancer. This first report with a limited

number of patients needs further confirmation, but cautious

optimism seems warranted that we may finally make

some progress in differentiating between the tiger and the

pussycat.

Conflicts of interest: The author has nothing to disclose.

References

[1] Singh D, Febbo PG, Ross K, et al. Gene expression correlates of clinical

prostate cancer behavior. Cancer Cell 2002;1:203–9.

E U R O P E A N U R O L O G Y 5 6 ( 2 0 0 9 ) 2 1 5 – 2 2 0 219

[2] Foekens JA, Atkins D, Zhang Y, et al. Multicenter validation of a gene

expression-based prognostic signature in lymph node-negative pri-

mary breast cancer. J Clin Oncol 2006;24:1665–71.

[3] Groskopf J, Aubin SM, Deras IL, et al. APTIMA PCA3 molecular urine

test: development of a method to aid in the diagnosis of prostate

cancer. Clin Chem 2006;52:1089–95.

[4] Bill-Axelson A, Holmberg L, Filen F, et al. Radical prostatectomy

versus watchful waiting in localized prostate cancer: the Scandina-

vian prostate cancer group-4 randomized trial. J Natl Cancer Inst

2008;100:1144–54.

[5] Suardi N, Capitanio U, Chun FK, et al. Currently used criteria for

active surveillance in men with low-risk prostate cancer: an analysis

of pathologic features. Cancer 2008;113:2068–72.

Kurt Miller

Department of Urology, Charite Berlin, Hindenburgdamm 30,

12200 Berlin, Germany

E-mail address: miller@medizin.fu-berlin.de

DOI: 10.1016/j.eururo.2009.04.015

Re: Surveillance and Deferred Treatment for LocalizedProstate Cancer. Population Based Study in the NationalProstate Cancer Register of SwedenStattin P, Holmberg E, Bratt O, Adolfsson J, Johansson J-E,

Hugosson J; National Prostate Cancer Register

J Urol 2008;180:2423–30

Experts’ summary:

In this Swedish study, the extent of watchful waiting and

active surveillance (ie, deferred treatment for patients with

localized prostate cancer) were evaluated. In Sweden, the

national prostate cancer registry is mandatory and covers

98% of all tumor patients. Between 1997 and 2007, 8304

patients with incident prostate cancer were identified, includ-

ing patients with clinically localized tumors T1 or T2, N0 or Nx,

and M0 and Mx and a prostate-specific antigen (PSA) level

<20 ng/ml. Patients were studied at time of diagnosis and for 4

yr thereafter.

Of all patients, 26% were put on surveillance, whereas 48%

underwent radical prostatectomy, 20% underwent radio-

therapy, and 5% underwent hormonal treatment. Men on

surveillance had significantly fewer aggressive tumors than

those treated immediately. After 4 yr, 34% of the men on

surveillance had had received treatment with radical

prostatectomy, radiotherapy, or hormonal treatment, and

66% of the patients initially managed with active surveillance

remained untreated. The authors conclude that in Sweden,

active surveillance was a relatively common treatment

option for patients <70 yr old in the period studied.

Expert’s comments:

Scandinavian countries have a long tradition of conservatively

managing men with prostate cancer. While the rest of the

world became more and more aggressive in the treatment of

even the smallest tumors, a relatively larger percentage of

patients were not treated initially in Sweden. It is only in

recent times that expectant management or active surveil-

lance have gained attention in other countries for smaller, less

aggressive tumors. But what are less aggressive tumors? Clear

and uniformly accepted criteria are still lacking for whom

to put on watchful waiting or active surveillance. Many

would agree that a Gleason score �6, a PSA <10 ng/ml, and

T1c to T2a represent good-risk tumors. Considering that

these criteria are found in approximately 50% of all newly

diagnosed prostate cancers, we are talking about a

significant number of patients for whom treatment might

not, or not immediately, be necessary [1].

Stattin et al did a wonderful job in taking advantage of

one of the most complete cancer registries in the world.

They add an important set of data on how to manage

patients with less aggressive tumors. From earlier studies,

we know that good-risk tumors remain so, even up to 20 yr

[2].

It is reassuring to urologists and to patients that active

surveillance does not mean just postponing treatment for a

few years and, consequently, losing precious time. It is

rather a long-term option for many patients, given proper

tumor selection and close follow-up.

In my opinion, we are still underutilizing surveillance as

a management option, thus treating too many men with

prostate cancer. Studies like this one may help us to find a

better way of handling this frequent tumor.

Conflicts of interest: The author has nothing to disclose.

References

[1] Klotz L. J Clin Oncol 2005;23:8165–9.

[2] Albertsen PC, et al. JAMA 2005;293:2095–101.

Thomas Gasser

University of Basel, Kantonsspital Liestal, Rheinstrasse 26,

4410 Liestal, Switzerland

E-mail address: thomas.gasser@ksli.ch

DOI: 10.1016/j.eururo.2009.04.016