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EUROPEAN UROLOGY 65 (2014) 1178–1183

available at www.sciencedirect.com journal homepage: www.europeanurology.com

Prostate Cancer

Transrectal Saturation Technique May Improve Cancer Detection as an Initial Prostate Biopsy Strategy in Men with Prostate-specific Antigen <10 ng/ml Yong-Hong Li a,c,y, Ahmed Elshafei a,y, Jianbo Li b, Michael Gong a, Luay Susan a, Khaled Fareed a, J. Stephen Jones a,* a

Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA;

c

Department of Urology, Cancer Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China

b

Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA;

Article info

Abstract

Article history: Accepted May 24, 2013 Published online ahead of print on June 3, 2013

Background: Using transrectal saturation prostate biopsy (SPBx) as an initial strategy remains a controversial topic. Objective: To compare SPBx with extended prostate biopsy (EPBx) as an initial biopsy template in a large sequential cohort study. Design, setting, and participants: We reviewed 438 men with initial SPBx and 3338 men who underwent initial EPBx between January 2002 and October 2011. Intervention: Office-based SPBx under periprostatic local anesthesia. Outcome measurements and statistical analysis: The yield of SPBx was compared with EPBx. Multivariable logistic regression models addressed cancer detection (CD) and cancer characteristics. Results and limitations: Overall CD was 51.6% and 42.6% in men who underwent initial SPBx and EPBx, respectively. Multivariate analysis confirmed that SPBx was an independent predictor factor correlated with the CD (odds ratio [OR]: 1.66; 95% confidence interval [CI], 1.30–1.92). Stratified by prostate-specific antigen (PSA) values, CD was higher in SPBx compared with EPBx, 47.1% versus 32.8% (OR: 2.00; 95% CI, 1.19–3.38) in patients with a PSA <4 ng/ml and 50.9% versus 42.9% in patients with a PSA from 4 ng/ml to 9.9 ng/ml (OR: 1.62; 95% CI, 1.20–2.20). By contrast, SPBx did not increase CD in men with a PSA >10 ng/ml (60.0% vs 61%; OR: 1.42; 95% CI, 0.70–2.89). There was no significant difference in the detection of insignificant cancer ( p = 0.223) or low-risk cancer ( p = 0.077) between the two biopsy schemes. The limitation of our study is its retrospective nature and inhomogeneity. Conclusions: Compared with EPBx, SPBx significantly increases CD as an initial biopsy strategy in men with a PSA <10 ng/ml without a significant increase in the detection of insignificant cancer. These findings suggest that SPBx may merit further investigation as an initial biopsy strategy in men with a PSA <10 ng/ml in hopes of avoiding repeat biopsy for missed malignancy during the initial biopsy. # 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Keywords: Prostate Biopsy Prostate-specific antigen Prostatic neoplasms

y Equal contribution. * Corresponding author. Glickman Urological and Kidney Institute, Cleveland Clinic, Glickman Tower (Q Building), 9500 Euclid Avenue, Cleveland, OH 44195. Tel. +1 216 476 0757. E-mail address: [email protected] (J.S. Jones).

1.

Introduction

In 1989, Hodge et al. [1] introduced sextant systematic transrectal ultrasound-guided prostate biopsy (PBx), which

remained the primary method of diagnosing prostate cancer (PCa) until the late 1990s. However, adding four to eight cores from the lateral peripheral zone, which is defined as extended PBx (EPBx), significantly increases cancer detection (CD)

0302-2838/$ – see back matter # 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.eururo.2013.05.047

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without demonstrable increased morbidity and without increasing the detection of clinically insignificant PCa [2]. Thus EPBx obtaining 10–14 cores has become the most widely accepted method as the initial PBx [2,3]. Theoretically, adding even more biopsies to areas not sampled by the extended technique should increase CD, although this has the potential to identify greater numbers of insignificant cancers. The concept led to the introduction of transrectal saturation PBx (SPBx), in which 20 cores are obtained in a systematic fashion [2,4]. Multiple authors have demonstrated that SPBx improves CD in the repeat biopsy population [5,6]. However, using SPBx as an initial strategy remains unsupported by the literature [2,7–14]. We previously reported that SPBx did not increase the CD in a 2006 pilot study comparing 139 men who underwent SPBx with 87 men undergoing EPBx [7]. A follow-up report further failed to support initial SPBx. We now report the mature series of 438 men who had undergone initial SPBx to outcomes for EPBx in a group of patients almost three times larger than the pilot series.

four urologists (J.S.J., K.F.) did not pursue it for initial biopsy after that observation. Importantly, the SPBx cases were consecutive for all surgeons in this group, ending only when the preliminary data analysis suggested that the SPBx did not provide additional benefit in the initial biopsy session. The remaining two urologists continued to perform SPBx for a period after that time based on their interest in fully defining its role in this setting. We compared 3338 men with a 12- to 14-core biopsy scheme (EPBx group) with 438 men with a 20-core biopsy scheme (SPBx group). In the EPBx group, we performed a 12- to 14-core scheme as previously described [5]. In the SPBx group, we performed 24-core transrectal SPBx in the beginning as previously described [7]. Based on the fact that our initial studies identified no improvement of CD and failed to identify unique cancers in parasagittal cores from these sectors, we progressed to a biopsy scheme of 20 cores focused on the lateral and apical aspects of the gland as subsequently described [15]. Pathologic assessment included variables as shown in Table 2. Insignificant PCa was defined according to the Epstein criteria: PSA density (PSAD) 0.15 ng/ml per gram, Gleason score 6, fewer than three positive cores, and <50% cancer involvement in any core [16]. Recognizing that these criteria were developed in the sextant biopsy setting, we also evaluated outcomes for low-risk PCa as defined according to the D’Amico criteria [17].

2.2.

2.

Patients and methods

2.1.

Procedure

Statistical analysis

Data were presented as means with standard deviations and medians with interquartile range, counts, or frequencies with percentages or proportions. Comparisons between groups were done using the From our institutional review board (IRB)-approved PBx database, we

Wilcoxon rank-sum test for normally distributed continuous variables,

reviewed 3776 consecutive men who underwent initial PBx by the EPBx

the Student t test for non-normally distributed continuous variables, and

or SPBx technique from January 2002 to October 2011. Men with the

the x2 test for categoric variables.

number of cores not eligible for the EPBx or SPBx categories (<12 cores or

Multivariable logistic regression was used to assess the effect of the

from 15 to 19 cores) or repeat PBx patients were excluded. Indications to

procedures on CD and to identify factors that influence CD. Odds ratios

perform an initial PBx were prostate-specific antigen (PSA) 2.5 ng/ml

(ORs) were estimated with 95% confidence intervals (CIs). For continu-

and/or abnormal digital rectal examination (DRE).

ous variables the OR estimation was based on between the 25th and 75th

Four urologists (J.S.J., M.G., L.S., K.F.) performed both SPBx and EPBx;

percentiles. The Cochran-Mantel-Haenszel x2 test was also used for

other urologists only performed EPBx. The urologists who performed

common OR estimation for strata of a continuous variable. The Fisher

SPBx did so by choosing a start date and then performing this procedure

exact test was then used for OR estimation for each stratum.

on all consecutive patients. Our initial experience did not appear to

All analyses were done using the statistical software package R v.2.15

support SPBx for initial biopsy as published at that time, so two of the

(R Development Core Team, www.r-project.org) with its base package

Table 1 – Patient characteristics (n = 3776) Variables

Age, yr, mean (SD) Race, n (%) White Black Other Family history of PCa, n (%)* Abnormal DRE, n (%) PSA level, ng/ml, median (IQR) PSA <4.0 ng/ml, n (%) PSA 4.0–9.9 ng/ml, n (%) PSA 10 ng/ml, n (%) %fPSA, mean (SD)* Total prostate volume, ml, median (IQR)* PSAD, median (IQR)* Total cores, median (IQR) PCa cases, n (%)

SPBx group n = 438 64.2 (9.3) 360 (82.2) 52 (11.9) 26 (5.9) 74 (19.5) 60 (13.7) 5.6 (4.2–7.9) 85 (19.4) 283 (64.6) 70 (16.0) 17.9 (8.1) 40.0 (27.0–56.0) 0.13 (0.09–0.20) 20 (20–24) 226 (51.6)

EPBx group n = 3338 63.8 (8.8) 2659 (79.7) 543 (16.3) 136 (4.1) 655 (22.1) 773 (23.2) 5.0 (3.9–7.7) 877 (26.3) 2023 (60.6) 438 (13.1) 17.9 (8.9) 38.0 (29.0–51.0) 0.13 (0.09–0.20) 12 (12–14) 1422 (42.6)

p value

0.252 0.213 0.018 0.071 0.266 <0.001 0.281 0.015 0.431 0.154 0.570 0.203 0.09 <0.001 <0.001

%fPSA = percentage of free to total PSA; DRE = digital rectal examination; EPBx = extended prostate biopsy; IQR = interquartile range; PCa = prostate cancer; PSA = prostate-specific antigen; PSAD = PSA density; SD = standard deviation; SPBx = saturation prostate biopsy. * 433 patients with unknown family history of PCa, 2246 patients without %fPSA, 648 patients with no total prostate volume, and 648 patients with no PSAD.

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Table 2 – Cancer characteristics (n = 1668) Variables

Positive cores, median (IQR) Percentage of cores involvement, %, median (IQR) Maximum cancer involvement core, %, mean (SD) Cancer grade Low grade (Gleason score 6), n (%) High grade (Gleason score 7), n (%) Clinically insignificant PCa, n (%) D’Amico ‘‘low-risk’’ PCa, n (%)

SPBx group n = 226

EPBx group n = 1422

4 (1–8) 16.7 (5.0–35.0) 42.5 (32.1) 113 113 48 97

p value

3 (2–6) 25.0 (14.3–50.0) 44.6 (31.9)

(50.0) (50.0) (21.2) (42.9)

589 833 254 523

0.133 <0.001 0.345

(41.4) (58.6) (17.9) (36.8)

0.015 0.015 0.223 0.077

EPBx = extended prostate biopsy; IQR = interquartile range; PCa = prostate cancer; SD = standard deviation; SPBx = saturation prostate biopsy.

[(Fig._1)TD$IG]

Fig. 1 – Multivariate logistic regression analysis of variables associated with prostate cancer detection. CI = confidence interval; DRE = digital rectal examination; OR = odds ratio; PSA = prostate-specific antigen.

and regression modeling strategies package. All statistics were considered significant at the level of a = 0.05.

3.

Results

Table 1 summarizes the demographic and clinical data. There were no significant differences regarding age, family history of PCa, total PSA, percentage of free to total PSA, total prostate volume, or PSAD. However, we did find more black men and more men with an abnormal DRE in the EPBx group compared with the SPBx group. Overall, CD was higher in men with SPBx than EPBx (51.6% vs 42.6%; p < 0.001). Table 2 lists the characteristics of PCa in each group. There were no significant differences regarding cancer volume based on the number of positive cores and maximum percentage of cancer involvement. We divided PCa grade into low-grade (Gleason score 6) and highgrade (Gleason score 7) subgroups. A higher rate of lowgrade PCa was detected in the SPBx group (50.0% vs 41.4%; p = 0.015). Nevertheless, SPBx did not detect a higher rate of clinically insignificant PCa (21.2% vs 17.9%; p = 0.223) or low-risk PCa (42.9% vs 36.8%; p = 0.077). Figure 1 lists the results of the multivariate logistic regression analysis of factors associated with the detection of PCa. SPBx, older age, black race, higher PSA, family history of PCa, abnormal DRE, and lower total prostate volume correlated with the positive diagnosis of PCa. The

OR for detecting PCa was 1.66 (95% CI, 1.30–2.12) for SPBx compared with EPBx. We further analyzed the CD according to biopsy strategy stratified by PSA values (Table 3). CD was 47.1% and 32.8% in the SPBx and EPBx group, respectively, when PSA was <4 ng/ml ( p = 0.008). CD was also increased in patients with SPBx when PSA was between 4 ng/ml and 9.9 ng/ml (50.9% vs 42.9%; p = 0.011). Therefore, men who underwent SPBx experienced improved PCa detection by 25.6% than EPBx when PSA was <10 ng/ml. By contrast, no significant benefit was found for SPBx when PSA was 10 ng/ml (60.0% vs 61.0%; p = 0.879). Multivariate logistic regression analysis of variables associated with CD stratified by PSA value showed the SPBx protocol was an independent factor when PSA was

Table 3 – Prostate cancer detection rate according to biopsy strategy stratified by prostate-specific antigen values PSA, ng/ml

Cancer detection rates, % (no. cancer/total) SPBx group

<4 4–9.9 10 >20

47.1 50.9 60.0 76.9

(40/85) (144/283) (42/70) (10/13)

p value

EPBx group 32.8 42.9 61.0 87.0

(288/878) (867/2022) (267/438) (107/123)

0.008 0.011 0.879 0.363

EPBx = extended prostate biopsy; PSA = prostate specific antigen; SPBx = saturation prostate biopsy.

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Table 4 – Multivariate logistic regression analysis of variables associated with cancer detection stratified by prostate-specific antigen value PSA <4 ng/ml Variables

OR (95% CI)

SPBx Age PSA Abnormal DRE Total prostate volume Family history of PCa Black race

2.00 1.57 7.41 1.74 0.49 1.74 0.93

PSA 4–9.9 ng/ml p value

(1.19–3.38) (1.21–2.06) (3.72–14.77) (1.16–2.60) (0.37–0.65) (1.22–2.48) (0.58–1.50)

0.009 <0.001 <0.001 0.007 <0.001 0.002 0.763

OR (95% CI) 1.62 1.98 1.29 2.62 0.56 1.61 1.48

(1.20–2.20) (1.65–2.37) (1.02–1.63) (1.92–3.59) (0.49–0.63) (1.26–2.07) (1.10–1.98)

PSA 10 ng/ml p value

OR (95% CI)

0.002 <0.001 0.037 <0.001 <0.001 <0.001 0.009

1.42 1.55 1.20 4.12 0.62 1.17 2.05

(0.70–2.89) (1.09–2.21) (1.08–1.34) (2.04–8.29) (0.51–0.75) (0.61–2.24) (1.06–3.99)

p value 0.334 0.016 <0.001 <0.001 <0.001 0.635 0.034

CI = confidence interval; DRE = digital rectal examination; OR = odds ratio; PCa = prostate cancer; PSA = prostate-specific antigen; SPBx = saturation prostate biopsy.

Table 5 – Prostate cancer detection according to biopsy strategy stratified by prostate-specific antigen density values PSAD

<0.15 0.15–0.24 0.25

Cancer detection rates, % (no. cancer/total)

p value

SPBx group

EPBx group

41.1 (88/214) 63.9 (69/108) 71.6 (53/74)

33.4 (529/1585) 52.2 (361/691) 70.6 (322/456)

0.025 0.024 0.860

EPBx = extended prostate biopsy; PSAD = prostate specific antigen density; SPBx = saturation prostate biopsy.

<4 ng/ml (OR: 2.00; 95% CI, 1.19–3.38) or between 4 ng/ml and 9.9 ng/ml (OR: 1.62; 95% CI, 1.20–2.20). However, SPBx protocol was not an independent factor when PSA was 10 ng/ml (OR: 1.42; 95% CI, 0.70–2.89) (Table 4).

We further analyzed PCa detection according to biopsy strategy stratified by PSAD values (Table 5). CD was 41.1% and 33.4% in the SPBx and EPBx groups, respectively, when PSAD was <0.15 ng/ml per gram ( p = 0.025). CD was also increased in patients with SPBx when PSAD was between 0.15 and 0.24 ng/ml per gram (63.9% vs 52.2%; p = 0.024). By contrast, no significant difference was found for PSAD 0.25 ng/ml per gram (71.6% vs 70.6%; p = 0.860). Table 6 lists the multivariate analysis for all variables associated with positive biopsies stratified by PCa grade that showed SPBx detected a higher rate of low-grade PCa (OR: 1.91; 95% CI, 1.44–2.55). However, there was no statistically significant difference in the detection of highgrade cancer (OR: 1.14; 95% CI, 0.86–1.51). Table 7 lists the multivariate analysis for all variables associated with positive biopsies stratified by PCa significance, which showed that SPBx increased the detection of

Table 6 – Multivariate logistic regression analysis of variables associated with positive biopsies stratified by cancer grade Low grade (GS 6) Variables SPBx Age PSA Abnormal DRE Total prostate volume Family history of PCa Black race

OR (95% CI) 1.91 1.71 1.03 0.95 0.71 1.47 1.39

(1.44–2.55) (1.44–2.02) (0.95–1.12) (0.72–1.24) (0.63–0.79) (1.16–1.87) (1.05–1.85)

High grade (GS 7) p value <0.001 <0.001 0.490 0.007 <0.001 0.002 0.021

OR (95% CI) 1.14 1.82 1.51 2.23 0.53 1.51 1.27

p value

(0.86–1.51) (1.57–2.11) (1.41–1.62) (1.80–2.76) (0.46–0.60) (1.22–1.88) (0.98–1.63)

0.363 <0.001 <0.001 <0.001 <0.001 <0.001 0.069

CI = confidence interval; DRE = digital rectal examination; GS = Gleason score; OR = odds ratio; PCa = prostate cancer; PSA = prostate-specific antigen; SPBx = saturation prostate biopsy.

Table 7 – Multivariate logistic regression analysis of variables associated with positive biopsies stratified by prostate cancer significance Insignificant PCa Variables SPBx Age PSA Abnormal DRE Total prostate volume Family history of PCa Black race

OR (95% CI) 1.97 1.73 0.51 0.83 1.09 1.36 1.25

(1.33–2.92) (1.36–2.20) (0.40–0.66) (0.56–1.23) (0.94–1.26) (0.96–1.91) (0.83–1.88)

Significant PCa p value 0.001 <0.001 <0.001 0.351 0.263 0.080 0.284

OR (95% CI) 1.45 1.88 1.61 1.66 0.46 1.60 1.39

(1.12–1.87) (1.64–2.17) (1.49–1.75) (1.35–2.03) (0.41–0.52) (1.31–1.96) (1.10–1.76)

p value 0.004 <0.001 <0.001 <0.001 <0.001 <0.001 0.007

CI = confidence interval; DRE = digital rectal examination; OR = odds ratio; PCa = prostate cancer; PSA = prostate-specific antigen; SPBx = saturation prostate biopsy.

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both insignificant PCa (OR: 1.97; 95% CI, 1.33–2.92) and significant PCa (OR: 1.45; 95% CI, 1.12–1.87), but with no higher rate of insignificant cancer. 4.

Discussion

Transrectal SPBx clearly increases the PCa detection in patients undergoing repeat biopsy [5,6]. Our pilot data suggested that SPBx did not appear to offer a benefit as an initial biopsy technique. However, only 139 men underwent SPBx in that study [7]. Despite those findings and other publications suggesting limited benefit in the initial biopsy setting, additional experience was accumulated in a consecutive fashion until each surgeon individually made the decision to stop using SPBx for the initial diagnosis. Thereafter, those surgeons continued to use SPBx for repeat biopsy but resumed EPBx for subsequent patients undergoing initial biopsy. In the current follow-up study, we compared 438 consecutive men undergoing initial SPBx with 3338 men with initial EPBx. Both univariate and multivariate analysis found that SPBx improved CD in men with PSA <10 ng/ml. Furthermore, multivariate analysis supported the conclusion that the impact of SPBx was not due to patient selection. Ravery et al. [8] compared 265 men who underwent 20core PBx with 1226 men undergoing 10-core PBx. They reported that the CD was 39.7% in the 10-core group and 51.7% in the 20-core group. The 20-core protocol increased CD by 30.2% overall compared with the 10-core procedure. Ploussard et al. [9] reported 2753 consecutive men who underwent a 21-core initial PBx scheme. The CD of each biopsy scheme (6, 12, or 21 cores) found that the 21-core PBx improved the CD by 6.7%. However, this investigation compared only 12 of the same 21 cores in each patient to determine whether additional cores in that patient changed CD. Jiang et al. [14] performed a systematic review and meta-analysis. They concluded that a SPBx scheme showed a significant advantage in PCa detection, but with no higher rate of insignificant cancer. However, some of the studies selected were not directly related to the current clinical question. For example, the abstract of the Pepe study suggested that the biopsy was transrectal, but the biopsy was actually transperineal. In addition, the risk difference in the systematic review was only 0.04 in men with PSA <10 ng/ml, significantly less than in our current report. By contrast, and similar to the results reported by Ravery et al., our study showed that the SPBx strategy increased CD by 25.6% in patients with PSA <10 ng/ml. In contrast, some smaller studies (including our pilot study) have found no significant benefit to a further increase of the number of biopsy cores to 13 or 14 or a saturation template as an initial PBx protocol. Nomikos et al. [11] reported 243 men who underwent EPBx compared with 139 men with a 24-core biopsy. Overall CD was 39.1% and 34.6%, respectively ( p = 0.43). However, the 10-core group had more men with abnormal DRE (21% vs 8.82%; p = 0.028). We note that these CDs are significantly lower than in our present report, and no multivariate analysis was

performed to identify whether their findings were due to the intervention (SPBx) or due to a difference in the populations. A review by Eichler et al. [12] concluded that schemes with 18–24 initial biopsy cores did not detect significantly more cancers. The authors concluded that the quality of reporting was often poor, and that some SPBx techniques often added cores from the central part of the gland where the likelihood of finding cancer is low [10,18,19]. Irani et al. [13] performed a randomized multicenter trial comparing 169 men with a 20-core PBx compared with166 men with a 10-core biopsy. The study detected a 16.2% increase in PCa detection in men with SPBx. However, this clinical difference did not reach statistical significance ( p = 0.213) due to a lack of statistical power, which they calculated at a larger difference in CD between 40% and 55%, and the actual power for a difference between 42% and 48.8% could be <50%. In addition, it is unclear if the authors took into account the variability among centers in the multivariable logistic analysis that could also influence the significance of the test. Although we found increased CD without increased identification of clinically insignificant cancer, we do not suggest that all men undergo SPBx in the initial biopsy. Our analysis showed that patients who underwent SPBx had significantly higher CD than EPBx only when the PSA was <10 ng/ml, especially with a PSA <4 ng/ml (47.1% vs 32.8%; p = 0.008) and when PSAD was <0.25 ng/ml per gram. Similarly, Ravery et al. [8] showed SPBx was more efficient, especially in patients with a PSA between 3 and 6 ng/ml (47.2% vs 28.1%; p = 0.001). Ploussard et al. [9] reported that the diagnostic yield of the 21-core protocol was >10% higher in men with a PSA <4 ng/ml, in prostates with volume >70 ml, and with a PSAD <0.20 ng/ml per gram. Therefore, if SPBx is to be considered for initial biopsy, it should be reserved for men with PSA <10 ng/ml. Even if CD is improved with SPBx, it is important to know if such an improvement in CD is clinically relevant. SPBx strategies have been hypothesized to have the potential for overdiagnosis. Ploussard et al. [9] showed that their 21-core protocol did not statistically increase the rate of detected insignificant PCa but increased the rate of low-grade cancer, which is reinforced by our findings. Irani et al. [13] showed that the Gleason score and cancer length measured on PBx cores were not significantly different. Ouzaid et al. [20] reported that PCa diagnosed only in a 21-core protocol is at least as aggressive based on radical prostatectomy specimens. In the current study, the detection of low-grade PCa was statistically increased, but there was no significant difference in the detection of insignificant PCa or low-risk PCa. The main limitation of our study is its retrospective nature, which is mitigated by the inclusion of all patients in our prospective IRB-approved database. The attending urologist’s preference was the main determinant of PBx protocol, so it is possible that the true incidence was different in the cohorts. However, we reemphasize that the saturation populations are in consecutive patients, making selection bias unlikely. From a methodological point of view, it would have been optimal to perform a prospective

EUROPEAN UROLOGY 65 (2014) 1178–1183

multicenter large sample clinical trial with patient randomization. However, there was no significant difference in the demographic or clinical characteristics between the two groups except for more patients with an abnormal DRE and more black men in the EPBx group (Table 1). This would be expected to make our findings less likely to be significant, so it further reinforces the potential benefit of an initial SPBx. Furthermore, multivariate analysis further supports the cause of these findings as the intervention (SPBx) rather than a difference in the populations. Finally, the biopsy schemes were not homogeneous in each group based on the inherent variability of technical performance.

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[3] Ukimura O, Coleman JA, de la Taille A, et al. Contemporary role of systematic prostate biopsies: indications, techniques, and implications for patient care. Eur Urol 2013;63:214–30. [4] Borboroglu PG, Comer SW, Riffenburgh RH, et al. Extensive repeat transrectal ultrasound guided prostate biopsy in patients with previous benign sextant biopsies. J Urol 2000;163:158–62. [5] Zaytoun OM, Moussa AS, Gao T, et al. Office based transrectal saturation biopsy improves prostate cancer detection compared to extended biopsy in the repeat biopsy population. J Urol 2011; 186:850–4. [6] Walz J, Graefen M, Chun FK, et al. High incidence of prostate cancer detected by saturation biopsy after previous negative biopsy series. Eur Urol 2006;50:498–505. [7] Jones JS, Patel A, Schoenfield L, et al. Saturation technique does not

5.

Conclusions

Transrectal SPBx significantly improved CD compared with EPBx in men with PSA <10 ng/ml as the initial biopsy technique without increasing the detection of clinically insignificant cancer. SPBx may merit further investigation for patients with PSA <10 ng/ml as an initial PBx scheme.

improve cancer detection as an initial prostate biopsy strategy. J Urol 2006;175:485–8. [8] Ravery V, Dominique S, Panhard X, et al. The 20-core prostate biopsy protocol—a new gold standard? J Urol 2008;179:504–7. [9] Ploussard G, Nicolaiew N, Marchand C, et al. Prospective evaluation of an extended 21-core biopsy scheme as initial prostate cancer diagnostic strategy. Eur Urol 2014;65:154–61. [10] de la Taille A, Antiphon P, Salomon L, et al. Prospective evaluation of a 21-sample needle biopsy procedure designed to improve the

Author contributions: J. Stephen Jones had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

prostate cancer detection rate. Urology 2003;61:1181–6. [11] Nomikos M, Karyotis I, Phillipou P, et al. The implication of initial 24-core transrectal prostate biopsy protocol on the detection of significant prostate cancer and high grade prostatic intraepithelial

Study concept and design: Jones, Y-H Li, Elshafei, Gong, Susan, Fareed. Acquisition of data: Y-H Li, Elshafei. Analysis and interpretation of data: Y-H Li, Elshafei, J. Li, Jones. Drafting of the manuscript: Y-H Li, Elshafei, Jones. Critical revision of the manuscript for important intellectual content: Jones, Gong, Susan, Fareed. Statistical analysis: J. Li, Y-H Li, Elshafei. Obtaining funding: None.

neoplasia. Int Braz J Urol 2011;37:87–93. [12] Eichler K, Hempel S, Wilby J, et al. Diagnostic value of systematic biopsy methods in the investigation of prostate cancer: a systematic review. J Urol 2006;175:1605–12. [13] Irani J, Blanchet P, Salomon L, et al. Is an extended 20-core prostate biopsy protocol more efficient than the standard 12-core?. A randomized multicenter trial. J Urol 2013;190:77–83. [14] Jiang X, Zhu S, Feng G, et al. Is an initial saturation prostate biopsy

Administrative, technical, or material support: Jones, Gong, Susan, Fareed.

scheme better than an extended scheme for detection of prostate

Supervision: None.

cancer? A systematic review and meta-analysis. Eur Urol 2013;63:

Other (specify): None.

1031–9. [15] Patel AR, Jones JS, Rabets J, et al. Parasagittal biopsies add minimal

Financial disclosures: J. Stephen Jones certifies that all conflicts of interest, including specific financial interests and relationships and

information in repeat saturation prostate biopsy. Urology 2004;63: 87–9.

affiliations relevant to the subject matter or materials discussed in the

[16] Bastian PJ, Mangold LA, Epstein JI, et al. Characteristics of insignifi-

manuscript (eg, employment/ affiliation, grants or funding, consultan-

cant clinical T1c prostate tumors. A contemporary analysis. Cancer

cies, honoraria, stock ownership or options, expert testimony, royalties,

2004;101:2001–5.

or patents filed, received, or pending), are the following: J. Stephen Jones:

[17] D’Amico AV, Whittington R, Malkowicz SB. Biochemical outcome

Photocure, Healthtronics, Cook; Khaled Fareed: Watson Pharmaceuti-

after radical prostatectomy, external beam radiation therapy, or

cals. The remaining authors have nothing to disclose.

interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998;280:969–74.

Funding/Support and role of the sponsor: None.

[18] Gore JL, Shariat SF, Miles BJ, et al. Optimal combinations of systematic sextant and laterally directed biopsies for the detection of

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