E U R O P E A N U R O L O G Y 5 6 ( 2 0 0 9 ) 8 8 1 – 8 8 6 883

the paper by King et al [2], the authors show that ERG-

rearranged PCa is enriched for PTEN loss. The authors provide

convincing evidence that ERG rearrangement has no effect by

itself but promotes invasive cancer only if combined with

PTEN loss. This new finding explains why ERG rearrange-

ments are less frequent in HGPIN than in invasive cancer

(approximately 15% vs 50%). In fact, ERG rearrangement and

PTEN loss make a perfect couple, as they combine enhanced

motility and invasion with increased proliferation. This paper

emphasizes that looking at only one gene at a time is too

simplistic and that we have to consider the complex

collaborative network of several molecules. The practical

implications of this study are two-fold. First, joint analysis of

ERG and PTEN status (eg, by fluorescent in situ hybridization

and immunohistochemistry on prostate biopsies) might

become a diagnostic tool for risk stratification in the future.

This is supported by Yoshimoto et al, who recently reported

that concurrent ERG rearrangement and PTEN deletion was

associated with early

recurrence of PCa [3]. Second, the study may pave the way to

new preventive or therapeutic strategies that target ERG and

PTEN or associated pathways

Conflicts of interest: The author has nothing to disclose.

References

[1] Tomlins SA, et al. Science 2005;31:644–8.

[2] King JC, et al. Nat Genet 2009;41:524–6.

[3] Yoshimoto M, et al. Mod Pathol 2008;21:1451–60.

Lukas Bubendorf

University of Basel, Institute for Pathology,

Schonbeinstrasse 40, 4031 Basel, Switzerland

E-mail address: bubendorfl@uhbs.ch

DOI: 10.1016/j.eururo.2009.08.007

Re: Temporary Balloon Occlusion of the Inferior VenaCava in Resection of Renal Tumor with Vena CavaThrombus Extension

Yang Y, Sun S, Xiao X, et al.

Urology 2009;73:645–8

Experts’ summary:

The authors report their experience with nephrectomy and

inferior vena cava (IVC) thrombectomy using endoluminal

occlusion of the cava. In their technique, a balloon catheter

is introduced cranially to the tumor thrombus but caudally

to the hepatic vein orifice. Fluoroscopic confirmation is

obtained prior to surgery. After clamping the infrarenal IVC

and contralateral renal vein, the balloon is inflated. In the

absence of hypotension, occlusion is maintained to provide

a bloodless field. Their technique is modified from Zini et al

[1]. Nine of 10 patients tolerated the procedure. The authors

reported no complications, and no bypass maneuvers were

used. The authors advocate this technique for level 2 and 3

thrombi.

Experts’ comments:

Such techniques of occlusion of the IVC cranially to the

tumor thrombus, first reported in 2006 by Zini et al [1], are

rare in the urologic oncology literature. Some trepidation

stems from the 8% tumor embolism rate reported by Zini et

al, as other authors report high mortality rates from

intraoperative tumor embolus [2]. We would add some

points.

First, the authors did not use transesophageal echocar-

diography (TEE). In our experience, TEE aids significantly in

level 2–4 thrombi. The cranial extent of the tumor can be

accurately judged, pulmonary vasculature can be examined

prior to thrombus manipulation, and intraoperative throm-

boemboli can be quickly identified and treated appro-

priately. The authors report no air embolism, but it is

unclear how this was confirmed. We recommend TEE for

every level 3 and 4 thrombus and for some of level 2

thrombus cases.

Second, Figure 3 in Yang et al appears to show the

balloon passing transdiaphragmatically. Such placement

would occlude the hepatic vessels, creating an ‘‘iatrogenic’’

Budd-Chiari syndrome, which can create significant intra-

operative surgical complications including bleeding, hepa-

tic congestion, and hypotension [3]. Extreme care should be

taken to ensure that the balloon does not occlude the ostia

of these vessels, and direct visualization is more suited to

this. Similarly, smaller lumbar and hepatic veins draining

into the cava may be obstructed by the balloon, causing

congestion with the potential for hypotension.

Third, our main concern with this technique is the

inability to confirm excision of all intracaval tumors. In level

3 thrombi, the cranial extent of the thrombus is the

diaphragm [4]. The placement of the balloon makes it

impossible to fully visualize the retrohepatic IVC and

confirm removal of the tumor.

In conclusion, such techniques have advantages; how-

ever, methods exist for safe, easily confirmed, and complete

excision of such tumors [5]. Such methods should be used

whenever possible.

Conflicts of interest: The authors have nothing to disclose.

References

[1] Zini L, Haulon S, Leroy X, et al. Endoluminal occlusion of the inferior

vena cava in renal cell carcinoma with retro- or suprahepatic caval

thrombus. BJU Int 2006;97:1216–20.

[2] Shuch B, Larochelle JC, Onyia T, et al. Intraoperative thrombus

embolization during nephrectomy and tumor thrombectomy: criti-

cal analysis of the University of California-Los Angeles experience. J

Urol 2009;181:492–8.

[3] Ciancio G, Soloway M. Renal cell carcinoma invading the hepatic

veins. Cancer 2001;92:1836–42.

E U R O P E A N U R O L O G Y 5 6 ( 2 0 0 9 ) 8 8 1 – 8 8 6884

[4] Neves RJ, Zincke H. Surgical treatment of renal cancer with vena cava

extension. Br J Urol 1987;59:390–5.

[5] Ciancio G, Livingstone AS, Soloway M. Surgical management of renal

cell carcinoma with tumor thrombus in the renal and inferior vena

cava: the University of Miami experience in using liver transplanta-

tion techniques. Eur Urol 2007;51:988–95.

Samir P. Shirodkara, Gaetano Cianciob,*, Michele Galluccic,

Mark S. Solowaya

aDepartment of Urology, University of Miami Miller School of Medicine and

Jackson Memorial Hospital, Miami, Florida, United States

bDepartment of Surgery, Division of Transplantation,

University of Miami Miller School of Medicine and

Jackson Memorial Hospital, Miami, Florida, United StatescDepartment of Urology, Regina Elena Cancer Institute, Rome, Italy

*Corresponding author. University of Miami Miller School of Medicine,

Department of Surgery, Division of Transplantation,

Post Office Box 012440, Miami, FL 33101, USA.

E-mail address: gciancio@miami.edu

DOI: 10.1016/j.eururo.2009.08.008

Re: Systematic Review of Pretreatment Prostate-SpecificAntigen Velocity and Doubling Time as Predictors forProstate Cancer

Vickers AJ, Savage C, O’Brien MF, Lilja H

J Clin Oncol 2009;27:398–403

Expert’s summary:

The authors performed a systematic review of the literature

on pretreatment prostate-specific antigen (PSA) dynamic

changes (ie, PSA velocity [PSAV] and PSA doubling time [PSA

DT]). Articles were chosen on the basis of a defined set of

criteria (intact prostate at the time of the final PSA

measurement and a minimum of two PSA determinations

prior to treatment, defined end points, and evaluation of

association of PSA dynamics with these). Of 1882 articles, 87

met the criteria. Main reasons for rejection were that the

study was not on human subjects or that no adequate

pretreatment PSA dynamic was measured or assessed. Of the

87 articles evaluated, 54% were positive reports, 34% were

negative, and 12% were inconclusive. Many of the studies

analyzed had serious methodological shortcomings, such as

verification bias and small sample size. The authors found

that there was little evidence that calculation of PSAV or PSA

DT in the detection of early prostate cancer in untreated

patients is beneficial or provides more relevant predictive

information than PSA alone. They nevertheless found some

evidence that PSAV may be of interest in men with prior

negative biopsy.

Expert’s comments:

What can be learned from this important article by Vickers et

al? First, although PSA dynamics are associated with many

end points, there is to date no clear evidence that

pretreatment PSA dynamics are of clinical value for early-

stage prostate cancer. Of all of the studies, only two compared

the accuracy of a statistical model incorporating both PSA and

a PSA dynamic with the accuracy of a model that included

PSA without the PSA dynamic: One study showed no

improvement in accuracy associated with PSAV; the other

showed some minor improvements but was subject to

verification basis.

Second, we urologists have to improve our method-

ological approach when doing studies. Few studies in this

analysis met the required standards and were flawed by

insufficient statistical power from too-small sample sizes or

verification bias such as considering men not requiring

biopsy according to PSA to be free of cancer. Sample-size

calculation and statistical counseling are easy to obtain. A

verification bias such as considering men with a PSA below

the threshold for biopsy to be free of cancer, as indicated in

the study by Vickers et al, should be obviated. We know

clearly from the placebo arm of the Prostate Cancer

Prevention Trial that up to 27% of patients with a PSA <4

ng/ml may harbor prostate cancer [1]. Given this verifica-

tion bias in the majority of studies on the analysis of PSA

dynamics, the potential of PSA dynamics might have been

falsely biased as a predictive tool in prostate cancer

screening and diagnosis. The recently published findings

of the European Randomized Study of Screening for Prostate

Cancer, providing evidence that PSA screening can reduce

the rate of death from prostate cancer by 20%, indicate a

high risk of overdiagnosis of prostate cancer based on PSA

screening [2]. The fact that 48 patients with a prostate

cancer detected by screening need to be treated to save 1

patient raises the need for better patient stratification and

selection for treatment. The data by Vickers et al do not

support the use of PSA dynamics in this context.

Third, PSA is of limited value for diagnostics as long as

the prostate is in situ because there are confounding factors,

such as benign prostatic hyperplasia, inflammation, infarc-

tion, mechanical stress, and drug interference with PSA

expression, that may influence PSA levels and dynamics

[3,4]. We frequently find prostate cancer due to benign

prostate enlargement as reported by Stamey et al [5].

Calculation of PSAV or PSA DT according to this review does

not improve detection rates, and prostate biopsies remain

the most reliable tool at our disposal for diagnosis of

prostate cancer. This needs to be taken into consideration

when screening patients and for patients on active-

surveillance protocols. PSA and PSA dynamics cannot be

used as a substitute for regular repeat biopsies. Rapid and

important changes in PSA levels and dynamics often are due

to prostatitis or other pathological states rather than to

prostate cancer. These causes need to be excluded and

should be treated adequately. Patients with persistent

elevations should undergo biopsy whenever there is a

therapeutic consequence.