EURURO Vol. 72 No. 3

Introduction

Whether or not active surveillance (AS) should be extended

to men with intermediate-risk (IR) prostate cancer (PCa) is a

highly debated issue. AS has emerged as a viable option for a

considerable number of men to counterbalance the risk of

overdiagnosis and overtreatment of clinically indolent

disease. Some AS protocols have included a small propor-

tion of men with Gleason score (GS) 7 disease

[1,2]

and,

more recently, National Comprehensive Cancer Network

(NCCN) guidelines

[3]

have listed AS an option for men with

‘‘favorable intermediate-risk’’ (FIR) PCa (GS 3 + 4, percent-

age of positive cores

50%, and only one additional IR

factor). However, most evidence supporting this risk

reclassification is indirect

[4]

, and many studies relied on

repeated biopsy results rather than on whole-specimen

pathology

[5] ,

providing a partial perspective of the

complete picture. Since its introduction, GS has been

regarded as the single most important element in risk

assessment

[6] .

Concerns about undergrading/staging at diagnosis and

missing the opportunity for cure if radical intervention is

delayed are the main drawbacks to the use of AS in the

setting of FIR PCa. Understanding the risk of harboring

unfavorable disease among this subgroup may foster more

appropriate selection of patients for AS protocols. The aimof

this study is to assess the risk of adverse characteristics in

men with very favorable risk GS 3 + 4 PCa and to identify

potential predictors of unfavorable features.

Patients and methods

2.1.

Patient selection and evaluation

All patients with biopsy GS 3 + 4, prostate-specific antigen (PSA)

10 ng/ml, and clinical stage cT2a or lower who underwent radical

prostatectomy (RP) at our institution between 2006 and 2014 were

included in this retrospective cohort analysis. All had a histologically

confirmed diagnosis of PCa (transrectal prostate biopsy) within 3 mo

before surgery. Due to the referral nature of our practice, a pathologist at

our institution reviewed all the biopsy slides. Thus the biopsy GS score

reported represents the result of our internal review

[7]

, and detailed

biopsy information was available for all of the patients. RP was performed

using an open retropubic, laparoscopic, or robot-assisted approach by

experienced urologists. Pelvic lymph node dissection was carried out

according to the operating surgeons’ preferences. Surgical specimens were

processed and analyzed using a standardized technique, as previously

described

[8]

. The institutional review board approved the study.

2.2.

Data collected

The clinical and biopsy variables included age at surgery, presurgery PSA,

PSA density (PSAD), clinical stage, primary and secondary Gleason grading

on biopsy, number of positive cores, number of total cores and percentage

of positive/total cores, maximum percentage of surface specimen tumor

involvement, presence of perineural invasion, and/or high-grade prostatic

intraepithelial neoplasia (HGPIN) in biopsy specimens.

Pathologic variables were primary and secondary GS, pT and pN

stage, and surgical margin status. American Joint Committee on Cancer

TNM 6th edition (2002) was used for pathologic staging, and GS was

assigned according to the 2005 International Society of Urological

Pathology (ISUP) modified Gleason scoring system

[9] .

Upgrade was

defined as GS 4 + 3 at definitive pathology. Patients with advanced

pathologic stage (pT3–T4 and/or pN1) and/or a pGS 4 + 3 were

considered as ‘‘unfavorable disease’’ at RP

[10]

. Pathologic stage pT2 or

lower and N0 was classified as ‘‘organ-confined disease,’’ whereas

‘‘specimen-confined disease’’ was pT2–pT3a PCa with negative margins

(R0) and negative lymph nodes (pN0)

[11] .

2.3.

Statistical analysis

In addition to descriptive statistics, we used the chi-square test for

comparing categorical variables and the Student

test or Wilcoxon rank

sum test for comparison of continuous variables. Clinical data (age,

PSAD, with logarithmic transformation, and clinical stage) and detailed

biopsy information were analyzed in multivariable prediction models

using logistic regression. The percentage of positive cores/total and

percentage of specimen surface tumor involvement were considered

both as continuous values and categorized as

50% or 50%, in

accordance with the cut-off suggested by the recent NCCN guidelines

update

[3]

. All tests were two sided with

value of 0.05.

Results

A total of 1190 patients were included.

Table 1

shows the

baseline demographic and clinical features of the cohort.

Median age at surgery was 62 yr (interquartile range

[IQR]: 57–67); PSA was 5.2 ng/ml (IQR: 4.3–6.6). The cT

stage was T1 in 812 patients (68%) and T2a in 378 (32%).

Median percentage of positive cores was 33% (IQR: 19–50),

and median surface area percentage of involvement was

25% (IQR: 10–50); perineural invasion was present in

273 patients (23%).

Table 2

lists the pathologic outcomes of the cohort. The

pT stage was 2a–2b in 274 (23%), 2c in 723 (61%), 3a in 144

(12%), and 3b in 48 (4%). Pathologic GS was 6 in 17%, 3 + 4 in

Table 1 – Demographic and preoperative features of the Gleason

score 3 + 4 very favorable intermediate-risk cohort

(

= 1190)

Age at surgery, yr

Median (IQR)

62 (57–67)

Range

37–79

Preoperative PSA, ng/ml

Median (IQR)

5.2 (4.3–6.6)

Clinical T stage (%)

T1c

812 (68)

T2a

378 (32)

Total biopsy cores

Median (IQR)

12 (12–14)

Positive biopsy cores

Median (IQR)

4 (3–6)

Positive cores, %

Median (IQR)

33 (19–50)

Surface area, %

Median (IQR)

25 (10–50)

HGPIN (%)

1064 (89)

Yes

126 (11)

Perineural invasion (%)

916 (77)

Yes

274 (23)

HGPIN = high-grade prostatic intraepithelial neoplasia; IQR = interquartile

range; PSA = prostate-specific antigen.

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

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