Review – Prostate Cancer

Approaches for Initial Prostate Biopsy and Antibiotic Prophylaxis

By: Guillaume Ploussarda , Vincenzo Scattonib, Gianluca Giannarinic and J. Stephen Jonesd

EU Focus, Volume 1 Issue 2, September 2015, Pages 109-116

Published online: 01 September 2015

Keywords: Prostate cancer, Biopsy, Detection rate, Core number, Transrectal, Imaging, Transperineal

Abstract Full Text Full Text PDF (459 KB) Patient Summary



Debate on the optimal technique to use as an initial prostate biopsy (PB) strategy is continually evolving.


To review recent advances and current recommendations regarding initial PB and antibiotic prophylaxis.

Evidence acquisition

A nonsystematic review of the literature was performed up to October 2014 using the PubMed and Embase databases. Articles were selected with preference for the highest level of evidence in publications within the past 5 yr.

Evidence synthesis

The decision to perform PB is still based on an abnormal digital rectal examination or increased prostate0specific antigen (PSA) level without clear consensus about the absolute cutoff. Several biomarkers have been suggested to improve PSA-based PB decision-making and minimize overdiagnosis and overtreatment. The random 12-core transrectal (TR) ultrasound-guided approach remains the standard-of-care technique for PB. A >12-core scheme may be considered as an alternative in a single patient given his clinical features (large volume, low PSA levels). Transperineal biopsies may only be considered as an alternative to the TR route in special situations. Nevertheless, given the increase in antimicrobial resistance, the impact on the post-biopsy sepsis rate should be assessed in well-designed clinical trials. Imaging-guided targeted PB strategies, combined or not with random PBs, may represent the future of prostate cancer diagnosis by reducing the number of PBs and improving decision-making.


The 12-core TR scheme remains the standard of care for initial PB. The actual trend for PB strategy, with the aim of avoiding overdiagnosis of very low-risk cancers, could rapidly change our current indications and techniques through new biomarkers and imaging-guided targeted strategies. Nevertheless, the cost-benefit balance of these techniques should be closely assessed in the setting of initial PB strategy.

Patient summary

This review highlights current recommendations for prostate biopsy and possible advances in the near future.

Take Home Message

The 12-core transrectal scheme remains the recommended method for initial prostate biopsy. Nevertheless, the debate is continually evolving and new strategies including transrectal saturation biopsy, transperineal approach, and image-guided targeted biopsies could provide interesting improvements in special situations.

Keywords: Prostate cancer, Biopsy, Detection rate, Core number, Transrectal, Imaging, Transperineal.

1. Introduction

Despite recent advances in prostate imaging, a prostate biopsy (PB) is the only way to establish a cancer diagnosis and is the most important predictor for clinical decision-making in men suspected of prostate cancer (PCa). The optimal initial PB strategy remains a controversial and timely topic. Since its introduction by Hodge et al [1], random, systematic, ultrasound (US)-guided transrectal (TR) needle biopsy has significantly improved PCa diagnosis in terms of the detection rate and pathologic characterization before treatment decisions [1]. Studies have demonstrated that a traditional sextant technique could miss substantial numbers of PCas, and that additional sampling of the lateral peripheral zone increases the diagnostic yield [2], [3], and [4]. The will to increase the detection rate and to improve pathologic characterization has led to new biopsy approaches, including TR saturation biopsy, the transperineal (TP) approach, and image-guided targeted PBs. Importantly, during the last decades, the role of PB has evolved from purely PCa detection to investigating how PB results can assist clinical management for patients. Thus, concerns about overdetection leading to overtreatment of low-risk PCa have greatly modified our clinical perception and the indications for PB.

This review focuses on evidence-based initial PB strategies and preventive antibiotic prophylaxis.

2. Evidence acquisition

A nonsystematic review of the literature was performed up to October 2014 using the PubMed and Embase databases. Articles were selected with a preference for the highest level of evidence in articles published within the past 5 yr. When available, articles with level 1 evidence were included. The search strategy included various algorithms and the following MeSH terms: prostate biopsy, prostate cancer, detection, transrectal ultrasound, diagnosis, imaging-guided, MRI, elastography, contrast-enhanced ultrasound, histoscanning, and transperineal. The search results were restricted to the English language without a year limit. Abstracts were reviewed for relevance to the defined review question, and the corresponding full papers were then assessed.

3. Evidence synthesis

3.1. Current recommendations for initial PB strategy

3.1.1. Indications

The decision to perform PB is usually based on an abnormal digital rectal examination (DRE) or increased prostate-specific antigen (PSA) level. While abnormal DRE necessarily indicates an initial PB irrespective of PSA level, debate regarding the pros and cons of PSA-based screening continues and there is no consensus on the absolute cutoff for performing PB.

The updated European Association of Urology (EAU) guidelines do not recommend widespread mass screening for PCa, but do strongly recommend early detection with PSA and biopsy in well-informed men [5]. The recent EAU recommendations suggest that the PSA level should be considered as a continuous parameter: the higher the value, the more likely the existence of PCa. A baseline PSA determination at 40–45 yr of age has been suggested, on which the subsequent screening interval can then be based. It has been demonstrated that baseline serum PSA ≥1.0 ng/ml at 45 yr of age and baseline serum PSA ≥2.0 ng/ml at 60 yr of age are associated with a significantly increased risk of PCa-related mortality and diagnosis of advanced or metastatic disease, even 25 yr after the initial PSA was obtained [5]. The EAU guidelines do not use a specific chronological age as a threshold for screening (Table 1 and Table 2).

Table 1 European Association of Urology recommendations for early detection of PCa

(1) Early detection of PCa reduces PCa-related mortality
(2) Early detection of PCa reduces the risk of being diagnosed and developing advanced and metastatic PCa
(3) A baseline serum PSA level should be obtained at 40–45 yr of age
(4) Intervals for early detection of PCa should be adapted according to the baseline PSA serum concentration
5) Early detection should be offered to men with a life expectancy ≥10 yr
(6) In the future, multivariate tools to predict clinical risk need to be integrated in the decision-making process

PCa = prostate cancer; PSA = prostate-specific antigen.

Table 2 Current recommendations according to different biopsy guidelines

EAU guidelinesAUA guidelinesNCCN guidelines
AntibioticsQuinolones are the drugs of choice (ciprofloxacin)MandatoryQuinolones; rectal culture before biopsy
Standard approachTRUSTRUSTRUS
Number of cores10–12 cores >12 cores not significantly more conclusive8–12 coresExtended pattern
Saturation biopsyIn special situationsOnly for repeat biopsiesOnly for repeat biopsies
Transperineal biopsyIn special situationsValid alternativeNo routine use

EAU = European Association of Urology; AUA = American Urological Association; NCCN = National Comprehensive Cancer Network; TRUS = transrectal ultrasound-guided.

By contrast, the 2014 National Comprehensive Cancer Network (NCCN) guidelines suggest a cutoff value of 3 ng/ml in association with percentage free PSA (fPSA) and PSA kinetics in PB decision-making [6]. Moreover, risk calculators can be used and predictive models such as nomograms that include more variables have been developed to improve the ability to counsel patients on the need for PB [7] and [8]. Since they have not been tested in randomized controlled trials (RCTs), the cut-point for risk associated with a reduction in PCa mortality remains unknown [6].

Currently, increasing age, ethnicity, and family history are established risk factors for PCa. Individuals with a positive family history of PCa are at twofold higher risk of having PCa [9]. While the recently revised guidelines of the EAU and the British National Institute for Health and Care Excellence do not comment on the management of men with a hereditary high risk of PCa, the Swedish 2014 guidelines recommend PB for men <50 yr who have two close relatives with PCa (at least one relative should be diagnosed at <75 yr), and for men with BRCA2 mutations and a suspicious DRE, PSA of 3 ng/ml, or PSA of 2–2.9 ng/ml with a doubling time of <2 yr [10].

Given the pitfalls of PSA testing, several new biomarkers have been suggested to improve PB or treatment decision-making and to minimize overdiagnosis and overtreatment. The Progensa PCA3 test is an FDA-approved test that has been commercially available since 2012. This test is generally used in men who had previous negative PBs, and may help in repeat PB decision-making. The exact PCA3 cutoff score that should be taken into account (25 or 35) is debatable. Recent studies have demonstrated a significant correlation between PCA3 and PCa significance [11], [12], and [13]. The consensus in most papers is that PCA3 is often negative in patients with indolent cancer. In a recent multi-institutional study in a clinical setting, Scattoni et al [14] added PCA3 to a multivariate base model consisting of total PSA, percentage fPSA, and prostate volume, but could not show a significant increase in predictive accuracy at initial PB [14].

Besides PCA3, the most promising biomarker in the last 2 yr is [–2]proPSA (p2PSA), a serum isoform of PSA, and its derivatives, namely percentage p2PSA (p2PSA as a proportion of fPSA) and the Beckman Coulter (La Brea, CA, USA) prostate health index (PHI; p2PSA/fPSA · √tPSA, where tPSA is total PSA), which may improve discrimination between men with and without PCa in patients with tPSA of 2–10 ng/ml. Preliminary investigations and observational prospective international studies have demonstrated that there is a strong association between these new biomarkers and cancer aggressiveness and Gleason score, and thus percentage p2PSA and PHI might result in avoidance of unnecessary PBs without missing significant PCa [15], [16], [17], and [18]. Recent studies comparing p2PSA and derivatives with other available biomarkers, in particular PCA3, revealed slightly higher accuracy for PHI than for PCA3, but an improvement in accuracy for their combination [17]. Moreover, it is notable that other biomarkers (TMPRSS2:ERG, 4Ks, miRNAs, circulating tumor cells) are emerging and may change our future practice. A recent report from the Dutch arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC) highlighted the value of adding these biomarkers, mainly PCA3 and a kallikrein panel (4K panel), to the ERSPC risk calculator [19]. In summary, the exact role of PHI and PCA3 and other established risk factors, especially in the prediction of higher Gleason grade at PB, remains a topic of controversy, and the international guidelines do not support the routine use of such biomarkers, except for the 2014 NCCN guidelines, which suggest use of percentage fPSA, PHI, and PCA3 in selected cases.

Consequently, it is still necessary to identify other clinically relevant risk factors for PCa that can stratify men by their risk of future clinically apparent PCa for whom PB should be performed as early as possible.

3.1.2. Technique

Needle guidance is via TRUS. The impact of the US probe type on the PCa detection rate has been questioned, with conflicting results. End-fire probes have been recommended to allow core samples to be taken more transversely and to improve sampling of far lateral and apical peripheral zones. Few studies have highlighted an improvement in the PCa detection rate for an end-fire compared to a side-fire probe, and a large retrospective series did not observe any significant difference [20] and [21]. The single prospective RCT comparing end-fire and side-fire probes was terminated early because of a lack of impact of probe type on the PCa detection rate after an initial set of PBs [22].

Several studies have demonstrated high rates of false-negative PBs using a sextant scheme. Given the need to target at least four additional cores from the lateral peripheral zone, the random 12-core TRUS approach is currently the standard-of-care technique for PB [5]. It is important to target the lateral peripheral zone on each side, at the apex, mid-gland, and base (six cores plus sextant cores). The impact of additional cores directed to hypoechoic and/or clinically felt lesions remains controversial, and this approach is not supported by a high level of evidence.

3.2. Ways to improve PB performance

3.2.1. Increasing the number of cores

The debate on the optimal number of cores that should be taken as an initial PB strategy remains open. Many urologists follow a 10–12-core scheme as an initial strategy according to widely used guidelines [5]. Nevertheless, several initial PB series used different schemes, largely based on centre experiences and preferences, with conflicting findings and contradictory recommendations [23], [24], [25], [26], and [27].

Most studies demonstrated a continuum of improvement in cancer detection with an increasing number of cores [24] and [25]. Saturation biopsies are commonly defined as schemes retrieving ≥18 cores (Fig. 1). Intuitively, the greater the number of biopsy cores, the higher the prostate sampling density and the higher the detection rate. Nevertheless, the statistical and clinical significance of such improvements is debatable. The main series comparing extended versus saturation biopsy strategies are summarized in Table 3[28], [29], and [30]. RCTs and large retrospective and prospective series exhibited conflicting results. A recent meta-analysis (that did not include the largest negative RCT conducted by Irani et al [29]) suggested that saturation PB provides a significant benefit in terms of detection rate without increasing the detection of insignificant PCa [31]. It is worth noting that several studies demonstrated that one strict extended biopsy scheme did not fit all, and support the relevance of regimens based on individual clinical settings [2], [24], and [25]. The diagnostic yield of saturation PB is highly modified by the presumed risk of PCa that can be evaluated by DRE, PSA, and prostate volume. Thus, subgroup analyses from large single-centre studies highlighted that a simple stratification by clinicopathologic factors might identify men who would benefit the most from a saturation PB strategy. As sampling accuracy tends to progressively decrease with increasing prostate volume, saturation PB schemes are more efficient in men with lower PSA levels, lower PSA density, and higher prostate volume [2], [24], [25], and [32]. Various cutoffs have been reported. The largest studies highlighted that the detection rate was significantly increased by the use of saturation schemes for prostate volume ≥55 ml, PSA <10 ng/ml, and PSA density <0.20 ng/ml/g [2], [21], [22], and [29]. Scattoni et al [24] showed that the optimal number and location of PB cores may be anticipated in each patient according to his clinical characteristics [24]. They built a user-friendly flow chart with the aim of detecting 95% of all cancers with a minimal number of cores (10–16 cores). The most advantageous PB scheme, in terms of core number and location, varied as a function of age, prostate volume, and DRE results.


Fig. 1 Extended versus saturation biopsy schemes. Lat = lateral; TZ = transition zone; Sext = sextant.

Table 3 Randomized controlled trials comparing extended 12-core to saturation biopsy, and TR to TP biopsy

Biopsy cores (n)Overall detection rate (%)p value
12-core vs saturation
Rodríguez-Covarrubias et al [28]15012 vs 1831410.02
Irani et al [29]33912 vs 204249NS
Park et al [30]23312 vs 183443NS
Takenaka et al [49]20012 in both arms5347NS
Hara et al [48]24612 in both arms4842NS

TR = transrectal; TP = transperineal; NS = not significant.

In saturation PB strategies, the diagnostic yield is mainly provided by the addition of far lateral cores [24] and [25]. Given its low additional detection rate during initial PB, a routine transition-zone biopsy should not be recommended. Targeting of hypoechoic lesions on US remains controversial [33] and [34].

The clinical relevance in improving the PCa detection rate is an increase in the diagnosis of clinically significant cancers without detection of indolent ones. Conversely, it has been hypothesized that saturation PB strategies increase the potential risk of overtreating patients whose tumors pose a very low risk to life. Overall, no significant increase in insignificant PCa detection has been observed, although the proportion of low-risk PCa cases eligible for active surveillance tended to increase when a saturation scheme was used [24], [25], [28], and [29].

Although Eichler et al [27] suggested a higher rate of adverse effects after more extended PB schemes, all contemporary studies reported that the major and minor complication rates between extended and saturation schemes were comparable [24], [28], [29], and [31]. The morbidity rates reported for saturation schemes were close to those reported for the standard extended procedure.

The impact of increasing the number of PB cores on staging improvement remains unclear. Some studies have indicated that saturation schemes provide more accurate assessment of the disease extent and aggressiveness [35]. The inclusion of patients in active surveillance protocols emphasizes the need for perfectly accurate staging strategies. It has been suggested that the rate of upstaging/upgrading, mainly in low-risk PCa, is lower when PCa diagnosis is based on saturation techniques [35]. Nevertheless, a high level of evidence is lacking, so no strong conclusions can be drawn.

To date, even if saturation PB improves the PCa detection rate without increasing the complication rate, its use as an initial biopsy strategy is not recommended. Nevertheless, a scheme of >12 cores may be considered as an evidence-based alternative to optimize PCa detection in a single patient, mainly for subgroups of patients with a large prostate volume and low PSA levels.

3.2.2. Targeting suspicious lesions

Random organ biopsies lead to inherent sampling biases and may be considered unsatisfactory because of a high false-negative rate and incomplete pathologic assessment. The PB landscape is evolving from random systematic biopsies to a targeted approach. Advances in PCa imaging have led to the promotion of image-guided targeted PBs based on magnetic resonance imaging (MRI) and/or improved US-based tools such as histoscanning and elastography. Such PB optimization might lead to better prebiopsy risk stratification, and to lower detection of insignificant PCa and lower false-negative rates.

Most imaging-guided procedures are based on MRI. The current gold standard is multiparametric MRI consisting of T2-weighted imaging coupled with at least two functional techniques. It has been suggested that the prevalence of suspicious lesions on MRI in biopsy-naive men is approximately 60% [36]. Three methods of fusing MRI for targeted biopsies have been reported: MRI-TRUS fusion, direct MRI-guided biopsies, and cognitive fusion. Cognitive fusion is the simplest procedure and has no additional costs; it is probably the most widely used method for MRI-targeted PB in spite of the risk of human error in extrapolating from MRI to TRUS [37].

The populations and MRI techniques reported in the literature exhibit strong heterogeneity, so current evidence favoring imaging-targeted strategies in the initial PB setting is debatable. Recent recommendations by an international expert panel have defined standards of reporting for MRI-targeted PB studies to facilitate comparisons between series and to improve their level of evidence [36]. MRI suspicion scores have also been developed (prostate imaging reporting and data system, PI-RADS) for better standardization of interpretation and reporting.

In a systematic review of the literature, Moore et al [36] compared standard and targeted PB approaches on a per core basis and found 30% positivity for targeted cores compared with 7% positivity for random cores. On a per patient basis, the overall PCa detection rate using targeted PBs was 48% compared with 36% for standard random PBs. Overall, combining systematic PBs with targeted PBs invariably improved the PCa detection rate among studies. However, in a recent systematic review of well-designed controlled studies, van Hove et al [38] did not find a significant advantage of targeted BP alone over random BP regarding the PCa detection rate in the initial PB setting, suggesting that targeted sampling cores could not supplant a whole gland systematic assessment [38].

The risk of missing cancer if men without any lesion on imaging do not undergo PB should be adequately evaluated. In men with normal imaging results, the PCa detection rate was approximately 20%; nevertheless, few of these nonvisible cancers were clinically significant according to PB findings. Indeed, evidence suggests that imaging-targeted PBs improve the detection of clinically significant PCa and could reduce the number of cores taken [39]. MRI suspicion of cancer has been associated with Gleason score upgrading. Targeted PBs were significantly better in detecting high-Gleason PCa [37], [39], and [40]. Improved detection of anterior tumors, which are easily missed with standard systematic PB, has also been suggested [41]. However, until there are further improvements in imaging, several groups recommend combined targeted and systematic sampling to detect the non-negligible number of clinically significant PCas not visible on MRI.

Several studies have assessed the benefit of other imaging-targeted PB techniques over systematic PBs. A prospective RCT revealed a 12% improvement in detection rate for a 10-core scheme including elastography-targeted cores when compared with a 10-core systematic scheme in line with series using each patient as his own control [42] and [43]. No clear benefit has been demonstrated for histoscanning and contrast-enhanced US, and future well-designed studies are awaited [44].

3.2.3. Changing the sampling route

The TP route is a well-known approach in urology and is generally reserved for saturation repeat PB indications. Advantages stem from direct access to the gland, which leads to potentially better sampling, particularly in the apical region [45]. It has also been suggested that entry via the perineal skin leads to a lower rate of postbiopsy infectious complications, because needle passage through the rectal mucosa is avoided [46]. Unlike the TR route, saturation TP PB usually requires general anesthesia, although the use of nerve block techniques has been reported. A TRUS probe and specialized equipment including a template grid and a stepper are generally used to guide the sampling.

A recent meta-analysis selected seven trials including three RCTs [47]. No significant differences in the PCa detection rate were observed when the number of cores was equal between the groups. The route did not impact on outcomes during sextant, extended, or saturation schemes. Stratification by PSA level or DRE findings did not seem to favor one route over another, and the location of positive PBs did not differ. The RCTs are listed in Table 3[48] and [49].

Related complications were also equivalent between TR and TP routes [47]. Advantages in terms of postbiopsy sepsis and readmission for infection have been suggested. Increases in antimicrobial resistance and infectious complications after PB might lead to reconsideration of the TP route in the near future. Nevertheless, no data of level 1 evidence are available to draw any strong conclusion [46].

To date, TP biopsy using fan or template-guided techniques as an initial strategy is considered an alternative to the standard TR route, mainly in special situations. TP biopsies may be useful in patients in whom the TR route is impossible (rectal amputation) or in whom a template-based pathologic assessment of the gland will modify the presumed treatment (focal therapy, active surveillance), mainly in the repeat PB setting.

3.3. Antibiotic prophylaxis

Although PB is generally considered a safe procedure, complications may occur, including bacteriuria, urinary tract infection, and sepsis. The overall frequency of infection can be as high as 6.3%, with a readmission rate ranging from 0.8% to 3% [50]. Rosario et al [51] reported a fever rate of 17.5% after PB. A recent systematic review of the literature demonstrated that antibiotic use significantly decreased bacteriuria (relative risk [RR] 0.25), bacteremia (RR 0.67), urinary tract infection (RR 0.37), and hospitalization (RR 0.13) [52]. Thus, regardless of the guidelines followed, antibiotics are recommended before PB. Quinolones are the antibiotic class most widely analyzed in clinical trials and are therefore the drugs of choice, given in more than 90% of cases [53]. The EAU guidelines recommend ciprofloxacin rather than ofloxacin. Optimal dosing and treatment time vary among centers and guidelines. A long-course 3-d regimen might significantly decrease the risk of bacteriuria, but did not affect other clinical outcomes such as hospitalization and urinary tract infection when compared with a single antibiotic dose. Given its noninferiority, a single dose is usually preferred and recommended. Comparisons between oral and systemic administration revealed equivalent outcomes. Alternative antibiotics of choice are third-generation cephalosporins and aminoglycosides via intramuscular or intravenous routes.

Concerns regarding increased antimicrobial resistance have been raised in recent years. This might have led to an increase in infectious complications and hospitalization for infection over time [54]. Most infections result from antimicrobial resistance to quinolones, as well as ampicillin and sulfamethozaxole-trimethoprim [50]. Several patient- and procedure-related risk factors for infectious complications have been identified, such as recent hospitalization, foreign travel, and a positive urine culture. Although the use of urine cultures and dipsticks is widespread, their need before biopsy remains unclear because of a lack of clinical trials. The most common risk factor for fluoroquinolone resistance is exposure to this antimicrobial class within 6 mo before biopsy; such exposure should lead the clinician to switch to alternative antibiotics. On the basis of the predictive value of fluoroquinolone-resistant organisms on rectal culture (reported in ∼20% of cases), the NCCN guidelines recently proposed a rectal culture in addition to urine culture before biopsy. Targeted antimicrobial prophylaxis might be associated with a lower incidence of postbiopsy infection [55]. However, no RCT favoring targeted antibiotics has been published to date. Topical rectal preparations are controversial. The use of enemas in addition to antibiotics reduced the risk of bacteremia without any improvements regarding infection or fever [52]. No clear benefit of prebiopsy povidone-iodine rectal cleansing has been demonstrated.

4. Conclusions

Debate on the optimal technique for an initial PB strategy is continually evolving. The 12-core TR scheme remains the recommended method for initial PB. Even if saturation PB improves the PCa detection rate without increasing complication rates, its use as an initial biopsy strategy is not recommended as routine. Nevertheless, a >12-core scheme may be considered as an evidence-based alternative to optimize PCa detection in a single patient given his clinical features, mainly for subgroups of patients with a large prostate volume and low PSA levels.

TP biopsies may only be considered as an alternative to the TR route in special situations. Given the increase in antimicrobial resistance, the impact on the postbiopsy sepsis rate should be assessed in well-designed clinical trials. The actual trend for PB strategy is to avoid overdiagnosis of very low-risk cancers without missing clinically significant ones. In this light, imaging-guided targeted PB strategies outperform random PB approaches and may represent the future of PCa diagnosis by reducing the number of PBs, improving disease staging, and thus aiding in treatment decision-making. Nevertheless, the cost-benefit balance for such imaging-based techniques should be closely assessed in the initial PB setting.

Author contributions: Guillaume Ploussard 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.

Study concept and design: Ploussard, Scattoni, Giannarini, Jones.

Acquisition of data: [author surnames separated by commas].

Analysis and interpretation of data: Ploussard, Scattoni, Giannarini, Jones.

Drafting of the manuscript: Ploussard, Scattoni.

Critical revision of the manuscript for important intellectual content: Scattoni, Giannarini, Jones.

Statistical analysis: None.

Obtaining funding: None.

Administrative, technical, or material support: None.

Supervision: Scattoni, Giannarini, Jones.

Other: None.

Financial disclosures: Guillaume Ploussard certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None.

Funding/Support and role of the sponsor: None.


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a Department of Urology, Saint-Jean Languedoc Hospital, Toulouse, France

b Department of Urology, Scientific Institute Hospital San Raffaele, University Vita-Salute, Milan, Italy

c Department of Experimental and Clinical Medical Sciences, Urology Unit, University of Udine, Academic Medical Centre Hospital Udine, Udine, Italy

d Department of Urology, Cleveland Clinic, Cleveland, OH, USA

Corresponding author.

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