[4] Heidenreich A, Bellmunt J, Bolla M, et al. EAU guidelines on prostate

cancer. Part 1: screening, diagnosis, and treatment of clinically

localised disease. Eur Urol 2011;59:61–71.

[5] Montorsi F, Wilson TG, Rosen RC, et al. Best practices in robot-

assisted radical prostatectomy: recommendations of the Pasadena

Consensus Panel. Eur Urol 2012;62:368–81.

Raymond C. Rosen

New England Research Institutes, Watertown, MA, USA

E-mail address: rrosen@neriscience.com.

http://dx.doi.org/10.1016/j.eururo.2013.10.049

Re: Short Term Outcomes of Prostate Biopsy in MenTested for Cancer by Prostate Specific Antigen: Prospec-tive Evaluation Within ProtecT Study

Rosario DJ, Lane JA, Metcalfe C, et al.

BMJ 2012;344:d7894

Expert’s summary:

Within the patient population of the UK ProtecT study, the

effects of prostatic biopsy in the context of a screening proto-

col were evaluated in 1147 men with a mean age of 62.1 yr

who underwent a transrectal 10-core biopsy under antibiotic

coverage, mostly with periprostatic anesthesia. Using ques-

tionnaires 7 d and 35 d afterward, the reported incidence was

pain in 43.6%, fever in 17.5%, hematuria in 65.8%, hematoche-

zia in 36.8%, and hemospermia in 92.6% (only 53% were

sexually active); patients rated these symptoms as major/

moderate in 7.3%, 5.5%, 6.2%, 2.5%, and 26.6%, respectively.

Immediately after the procedure, 10.9% reported that they

would consider a repeated biopsy a major/moderate problem,

but this percentage increased to 19.6% after 7 d, and 1.3% were

rehospitalized for complications. A strong association existed

between a negative attitude toward repeated biopsy and pain

as well as symptoms related to infection and bleeding. Be-

cause significant differences were documented within cen-

ters, the authors conclude that outcomes could be improved

and the use of subsequent health care reduced with more

effective administration of local anesthetics and antibiotics.

Expert’s comments:

This well-conducted study, with a high response rate,

addresses the issue of effects of prostatic biopsy in the par-

ticularly sensitive context of screening protocols. These oth-

erwise healthy men were biopsied only for prostate-specific

antigen elevation, without associated prostatic symptoms.

One of the criteria for the choice of a screening test is that

the screened population should find it acceptable.

This study reveals that prostatic biopsy was well tolerated

by most patients but was associated with relevant symptoms

in a minority, which in turn affected the attitude toward a

repeat procedure. These observations in asymptomatic male

patients undergoing prostate cancer screening represent one

of the reasons why the US Preventive Services Task Force

recently recommended against it [1].

Within the European Randomized Study of Screening

for Prostate Cancer study, sextant biopsy caused hematos-

permia in 50.4% of men, hematuria in 22.6%, fever in 3.5%,

rehospitalization in 0.4%, and prostatitis in 0.5% [2]. In the

United States, a retrospective analysis of the Surveillance

Epidemiology and End Results prostatic biopsies database,

consisting of older subjects (median age: 73 yr), documented

a 2.65-fold increased risk of hospitalization within 30 d (6.9%

vs 2.7% in controls) [3]. There is a recent trend toward an

increase of infective biopsy complications due to increased

germ resistance to fluoroquinolones [4], and the present

consensus is that local anesthetic given as a periprostatic

nerve block is more effective than intrarectal instillation in

alleviating pain from ultrasound-guided prostatic biopsy [5].

Conflicts of interest: The author has nothing to disclose.

References

[1] Moyer VA. Screening for prostate cancer: U.S. Preventive Services Task

Force recommendationstatement. Ann Intern Med 2012;157:120–34.

[2] Raaijmakers R, Kirkels WJ, Roobol MJ, et al. Complication rates and

risk factors of 5802 transrectal ultrasound-guided sextant biopsies of

the prostate within a population-based screening program. Urology

2002;60:826–30.

[3] Loeb S, Carter HB, Berndt SJ, et al. Complications after prostate

biopsy: data from SEER Medicare. J Urol 2011;186:1830–4.

[4] Wagenlehner FME, van Oostrum E, Tenke P, et al. Infective complica-

tions after prostate biopsy: outcome of the Global Prevalence Study of

Infections in Urology (GPIU) 2010 and 2011, a prospective multina-

tional multicentre prostate biopsy study. Eur Urol 2013;63:521–7.

[5] Tiong HY, Liew LCH, Samuel M, et al. A meta-analysis of local

anesthesia for transrectal ultrasound-guided biopsy of the prostate.

Prost Cancer Prostatic Dis 2007;10:127–36.

Cesare Selli

Department of Urology, University of Pisa, Pisa, Italy

E-mail address: c.selli@med.unipi.it.

http://dx.doi.org/10.1016/j.eururo.2013.10.050

Re: Prognostic Influence of the Third Gleason Grade inProstatectomy Specimens

Cedeno Dıaz OM, Fernandez Acenero MJ, Alvarez Fernandez E

Urol Oncol 2012;30:386–90

Experts’ summary:

In a review of 85 consecutive radical prostatectomy (RP) speci-

mens, Cedeno Dıaz et al. examine the prognostic significance of

tertiary growth patterns for prostate cancer (PCa), specifical-

ly analyzing recurrence-free survival. This effect was

assessed while controlling for multiple known prognostic

factors including age, clinical stage, Gleason score, capsular

invasion, extraprostatic extension, lymphatic, vascular, and

perineural invasion, and the presence of high-grade prostatic

intraepithelial neoplasia. Specimens were obtained from

men with clinically localized disease who underwent RP at

E U R O P E A N U R O L O G Y 6 5 ( 2 0 1 4 ) 4 9 7 – 5 0 1498

a single hospital between 1995 and 1997 with a mean follow-up

period of 114 mo.

The authors found that Gleason score 7 tumors (both

3 + 4 and 4 + 3) with higher tertiary grades displayed

statistically significant differences for recurrence-free

survival when compared with equally scored tumors that

lacked higher tertiary grades ( p = 0.03). Interestingly,

Gleason score 7 tumors with tertiary 5 foci had comparable

survival rates as specimens with Gleason score�8 ( p = 0.9).

The authors suggest that because the current binary grading

system does not take into account the existence of tertiary

growth patterns, it may exclude higher grade foci that

appear to be clinically significant. They conclude that

inclusion of a tertiary growth pattern in the pathologic

report should be considered and, when present, should

prompt clinicians to manage certain tumors as higher risk

lesions.

Experts’ comments:

The Gleason grading system has remained one of the most

powerful prognostic factors for PCa since its introduction

nearly four decades ago. But concern has been raised recently

regarding the clinical significance of high-grade tertiary pat-

terns within tumor specimens.

The literature supports the presence of tertiary Gleason

patterns in almost 20% of RP specimens, as well as an

increased risk of biochemical recurrence between that of

the same Gleason score category and that of the next higher

category [1,2]. However, the translation of this increase in

categorical stratification to changes in management has

been less obvious [3]. More recently, it was demonstrated

that tertiary pattern 5 in Gleason 7 PCa predicts earlier

biochemical recurrence and an overall poorer prognosis

than Gleason score 7 without pattern 5 [4]. Cedeno Dıaz

et al., despite a small sample size albeit with long-term

follow-up, also support that tertiary pattern 5 in Gleason

score 7 PCa has a significant and potentially treatment-

altering role in the management of PCa.

The presence of tertiary pattern 5 on RP pathology reports

should guide clinicians as they counsel patients regarding the

necessity for ‘‘high-risk’’ postoperative follow-up and may

open discussion for a low threshold for adjuvant radiation

and/or androgen-deprivation therapy.

Conflicts of interest: The authors have nothing to disclose.

References

[1] Epstein JI, Feng Z, Trock BJ, Pierorazio BM. Upgrading and down-

grading of prostate cancer from biopsy to radical prostatectomy:

incidence and predictive factors using the modified Gleason grad-

ing system and factoring in tertiary grades. Eur Urol 2012;61:

1019–24.

[2] Epstein JI. An update of the Gleason grading system. J Urol 2010;183:

433–40.

[3] Trock BJ, Guo CC, Gonzalgo ML, Magheli A, Loeb S, Epstein JI.

Tertiary Gleason patterns and biochemical recurrence after radical

prostatectomy: proposal for a modified Gleason scoring system.

J Urol 2009;182:1364–70.

[4] Whittemore DE, Hick EJ, Carter MR, Moul JW, Miranda-Sousa AJ,

Sexton WJ. Significance of tertiary Gleason pattern 5 in Gleason

score 7 radical prostatectomy specimens. J Urol 2008;179:516–22.

Zachary Klaassen, Junjian Huang, Alexander J. Tatem, Martha K. Terris*

Section of Urology, Department of Surgery, Medical College of

Georgia–Georgia Regents University, Augusta, GA, USA

*Corresponding author. Section of Urology, Medical College of

Georgia–Georgia Regents University, Augusta, GA, USA.

E-mail address: mterris@gru.edu (M.K. Terris).

http://dx.doi.org/10.1016/j.eururo.2013.10.051

Re: Topography of Lymph Node Metastases in ProstateCancer Patients Undergoing Radical Prostatectomy andExtended Lymphadenectomy: Results of a CombinedMolecular and Histopathologic Mapping Study

Heck MM, Retz M, Bandur M, et al.

Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2013.

02.007

Experts’ summary:

The authors’ objective was to evaluate the extent of pelvic

lymphadenectomy (PLND) during radical prostatectomy by

investigating the topography of lymph node (LN) metasta-

ses. Their work was based on the histopathologic and mo-

lecular evaluation of LNs dissected from a total of

52 patients, 15 intermediate risk and 37 high risk, who

underwent extended PLND up to the bifurcation of the aorta.

Histopathologic examination was performed in all LNs,

and LNs >3 mm in diameter underwent additional investi-

gation with quantitative reverse transcriptase-polymerase

chain reaction. The latter investigation confirmed the pres-

ence of metastasis in 32 of 35 histopathologically positive

LNs (91%) and revealed 95 involved LNs that were histo-

pathologically negative. The combination of the methods

just cited showed that positive LNs were present in the

obturator fossa and external iliac vessels in 71% of the cases.

Internal and common iliac vessels were involved in 16% and

13%, respectively. Among the node-positive cases, metasta-

ses were detected outside the obturator fossa and external

iliac vessels in 63%. In addition, 48% and 37% of the node-

positive cases involved the internal and common iliac LNs,

respectively. Isolated LN involvement was observed in 7% of

internal and 11% of common iliac regions in node-positive

patients.

Experts’ comments:

The current evidence is inadequate to propose an efficient

template for staging PLND with the least morbidity. The

difficulty is based on several issues that were not adequately

addressed [1]. A major problem is the lack of evidence regard-

ing the topography of the LNs that are more frequently

involved [1]. The pathologic examination was hampered by

the lack of strict methodology for LN examination and resulted

E U R O P E A N U R O L O G Y 6 5 ( 2 0 1 4 ) 4 9 7 – 5 0 1 499