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Prostate Cancer

A Clinician's Guide to Avoiding and Managing Common Complications During and After Robot-assisted Laparoscopic Radical Prostatectomy

By: Daniel Pucherila , Logan Campbella, Ricarda M. Bauerb, Francesco Montorsic, Jesse D. Sammona and Thorsten Schlommd

EU Focus, Volume 2 Issue 1, April 2016, Pages 30-48

Published online: 01 April 2016

Keywords: Robot-assisted radical prostatectomy, Prevention, Management, Complications

Abstract Full Text Full Text PDF (1,2 MB)

Abstract

Context

Robot-assisted radical prostatectomy (RARP) is on the advance globally, and it is essential for surgeons and patients to know the rates of perioperative complications.

Objective

To provide evidence-based clinical guidance on avoiding and managing common complications during and after RARP in the context of a comprehensive literature review.

Evidence acquisition

In concordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis 2015 statement guidelines, a literature search of the PubMed database from August 1, 2011, to August 31, 2015, using the predefined search terms robot* AND radical prostatectomy, was conducted. The search resulted in 653 unique results that were subsequently uploaded to DistillerSR (Evidence Partners, Ottawa, Canada) for team-based screening and processing of references.

Evidence synthesis

Overall, 37 studies met the inclusion criteria and were included. Median rate of overall complication was 12.6% (range: 3.1–42%). Most of the complications were minor (Clavien-Dindo grades 1 and 2). Grade 3 complications comprised the bulk of the major complications with a median rate of 2.7%; grade IV and V complications were exceedingly rare in all reports.

Conclusions

Despite continued adoption of the RARP technique globally, rates of overall complication remain low. Many of the complications experienced during and after RARP can be mitigated and prevented by experience and the implementation of safe techniques.

Patient summary

Despite continued adoption of the robot-assisted radical prostatectomy (RARP) technique globally, rates of overall and major complications remain low at 12.6% and 2.7%, respectively. Complications can be minimized and successfully managed using established techniques. RARP is a safe and reproducible technique.

Take Home Message

Despite widespread global adoption of the robot-assisted radical prostatectomy (RARP) technique, overall complications remain low. RARP is both technically feasible and reproducible. Perioperative RARP complications can be greatly minimized by the implementation of evidence-based practices.

Keywords: Robot-assisted radical prostatectomy, Prevention, Management, Complications.

1. Introduction

In 2010, an estimated 85% of radical prostatectomies (RPs) performed in the United States were conducted using the robotic platform [1], and over the last several years robot-assisted radical prostatectomy (RARP) has continued to gain preeminence globally [2]. It is essential for surgeons and patients to be aware of rates of perioperative complications, and several authors have conducted robust systematic reviews concerning this topic [3], [4], and [5]. In studies published through 2009 and utilizing the Clavien system, overall RARP complication rates ranged from 12% to 26%, and a meta-analysis of RARP outcomes through 2010 calculated a total perioperative complication rate of 7.8% [3] and [4]. Most recently, Novara et al. conducted a systematic review of studies through August 2011 specifically evaluating perioperative RARP complications and reported rates of overall complications ranging from 3% to 26% [5]. Therefore, given the rapid diffusion and adoption of this technique, a more contemporaneous assessment of published outcomes is warranted. However, the primary aim of this work is to provide clinicians with an evidence-based resource on how to avoid and manage common complications during and after RARP.

2. Evidence acquisition

We conducted a systematic review according to the Preferred Reporting Items for Systematic Review and Meta-analysis protocols (PRISMA-P) 2015 statement [6]. In compliance with PRISMA-P guidelines, our systematic review protocol was registered online with the International Prospective Registrar of Systematic Reviews (PROSPERO) on October 5, 2015 (registration number: CRD42015026812) and did not duplicate a prior systematic review of perioperative complications following RARP [5].

We conducted a literature search of the PubMed database from August 1, 2011, to August 31, 2015, using the predefined search terms “robot*” AND “radical prostatectomy.” Our search resulted in 653 unique results that were subsequently uploaded to DistillerSR (Evidence Partners, Ottawa, Canada), an Internet-based software that facilitates team-based screening and processing of references (https://distillercer.com). Four levels of review were undertaken: title screening, abstract screening, manuscript screening, and data extraction.

Two review authors (D.P. and L.C.) independently screened each title and abstract at levels 1 and 2, respectively. Titles consistent with the study aim and abstracts meeting the inclusion criteria were advanced to level 3, if unanimity was not achieved, conflicts were mediated and resolved by a third author (J.D.S.). At level 3, full-text articles were scrutinized to ensure all inclusion criteria were present. At level 4, data were extracted in accordance with desired outcomes. At level 4, reference lists of included studies were reviewed for pertinent references not captured in the literature search.

Studies were considered if published after August 1, 2011, and explicitly reporting perioperative rates of complication (excluding functional outcomes of continence and potency) following at least 100 consecutive RARPs. Both comparative and noncomparative studies were considered for inclusion. Studies reporting outcomes following simple prostatectomy for benign disease were excluded. Studies not in English, abstracts, reports from meetings, comments, and editorials were not considered. When studies reported outcomes from the same institution, only the most recent publication was included, unless reporting a different cohort or complication.

Although the sequential, level-based systematic review technique is commonly used, it is not without limitation. For example, the title of a paper may allude that the work is primarily about functional and oncologic outcomes yet not state explicitly that the text also includes data regarding perioperative complications. In this scenario, works that should be included may inadvertently be excluded. To combat this phenomenon, liberal criteria were used to advance a work from level 1 to 2; however, despite best efforts, some works may be erroneously excluded from this review. Even with this significant limitation, this methodology allows for the inclusion of most of the appropriate texts.

3. Evidence synthesis

3.1. Study selection

Figure 1 depicts the flowchart summarizing this systematic review. Our initial search yielded 659 records of which 10 were duplicates. Two records were added after bibliography review, and reviewers noted an additional two records after submission, resulting in 653 records screened. Adhering to the previously mentioned exclusion criteria, 591 records were excluded. Most of the exclusions were for non–English language, failure to report perioperative rates of complication, or series comprising <100 consecutive cases. Sixty-three full-text articles were assessed; 37 studies were ultimately included [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], and [43].

gr1

Fig. 1 Flowchart of the systematic review.

3.2. Overall complication rates and rates of complication by Clavien-Dindo classification

Table 1 summarizes the overall complication rates and rates of complication stratified by Clavien-Dindo grade. The median rate of overall complications was 12.6%, with a range of 3.1–42%. Most of the complications in each study were minor (Clavien-Dindo grades 1 and 2). Grade 3 complications comprised the bulk of major complications with a median rate of 2.7% (range: 0–9.5%). Grade 4 (range: 0–1%) and 5 (range: 0–0.5%) complications were exceedingly rare in all reports. Di Pierro et al. reported the highest rate of overall complication, 42% [28]. This group prospectively recorded and reported outcomes of the first 233 RARPs plus extended pelvic lymph node dissection (ePLND) cases performed by a single surgeon with experience in both laparoscopic (>50 cases) and open (>100 cases) approaches [28]. Upon review, the markedly higher rate of overall complication in this report is driven by 47 episodes of “pressure skin redness” recorded as a grade 1 complication. The incidence of “pressure skin redness” ranged from 27% early in their series and dropped to 5% following a technical modification in patient positioning [28]. The authors intentionally reported clinically insignificant events to fully characterize their learning curve, and they note that if these events were excluded, their overall complication rate would drop to 16% [28].

Table 1 Overall complication rates and rates of complication by Clavien-Dindo classification

StudyInstitutionCasesStudy designOverall complication (%)Minor complication,1–2 (%)Major complication, 3–5 (%)Grade 1 (%)Grade 2 (%)Grade 3 (%)Grade 4 (%)Grade 5 (%)
Ahmed et al. [8]George Washington University, USA1000Retrospective case series9.75.62.72.80.50
Yip et al. [13]Chinese University of Hong Kong, Hong Kong
Prince of Wales Hospital, Hong Kong, Queen Mary Hospital, Hong Kong
Princess Margaret Hospital, Hong Kong
Pamela Youde Nethersole Eastern Hospital, Hong Kong
235Retrospective case series7
Bae et al. [9]Kyungpook National University, Korea111Retrospective comparative12.610.81.81.891.800
Fuller et al. [18]Schulich School of Medicine, Western University, Canada305Prospective case series237.57.97.200.3
Bouchier-Hayes et al. [10]Royal College of Surgeons in Ireland, Ireland125Retrospective case series12.943.25.600
Zugor et al. [14]Prostate Center Northwest Gronau, Germany; RWTH Aachen University Hospital, Germany2000Retrospective comparative12.711.41.3
Ghazi et al. [19]University of Tromso, Norway1503Prospective case series10.03.042.80.20.1
Dogra et al. [11]Medanta institute, India
RML Hospital, India
190Retrospective case series27.47.89.59.50.50
Ploussard et al. [33]Hospital Henri Mondor, France1009Retrospective comparative4.70.73.600.20.1
Froehner et al. [17]Dresden University of Technology, Germany317Retrospective comparative333.2
Galfano et al. [43]Niguarda Ca’ Granda Hospital, Italy200Prospective comparative12.5111.51.500
Hashimoto et al. [20]Tokyo Medical University, Japan200Retrospective case series17.517.50710.5000
Stolzenburg et al. [25]University of Leipzig, Germany
University of Patras, Greece
100Retrospective case series14
Liss et al. [22]University of California Irvine, USA
Polisseni Robotic and Minimally Invasive Surgery Center, USA
1000Retrospective case series10.8
Brennhovd et al. [16]Oslo University Hospital, Norway1076Retrospective comparative3.420.70.60.1
Sejima et al. [23]Totter University Faculty of Medicine, Japan100Retrospective case series30281100
Seo do et al. [24]Eulji University, Korea100Retrospective case series17170
Musser et al. [32]Memorial Sloan Kettering Cancer Center, USA651Retrospective comparative4.43.30.30
Di Pierro et al. [28]Luzerner Kantosspital, Switzerland233Prospective case series422111100.50.5
Koo et al. [31]Yonsei University College, Korea154Retrospective comparative14.33.91.39.100
Garate et al. [35]Hospital Universitario de Caracas, Venezuela101Retrospective case series13112200
Gu et al. [30]University of Oklahoma Health Sciences Center, USA218Prospective comparative9.6
Babaian et al. [27]University of California Irvine, USA1000Retrospective comparative10.2216.70.50
Gagnon et al. [29]Vancouver Prostate Center and Department of Urologic Sciences, Canada200Retrospective case series22137200
Modi et al. [37]Rutgers Cancer Institute of New Jersey, USA751Retrospective case series8.55.50.133.10
Kumar et al. [36]University of Central Florida, USA800Retrospective comparative6.54.42.1
Tasci et al. [40]Dr. Sadi Konuk Training and Research Hospital, Turkey; Acibadem University School of Medicine, Turkey; Umraniye Training and Research Hospital, Turkey; Ankara Ataturk Training and Research Hospital, Turkey1499Retrospective case series6.11.92.90.60.30.1
Yumioka et al. [42]Totter University, Japan150Retrospective comparative24
Morgan et al. [38]University of Texas Southwestern Medical Center, USA381Retrospective comparative12.32.63.62.610
Akand et al. [34]Selcuk University, Turkey; Memorial Atasehir Hospital, Turkey; Memorial Antalya Hospital, Turkey120Prospective comparative11.756.700
Wagenhoffer et al. [41]Klinikum Ingolstadt, Germany100Retrospective case series115051

3.3. Rates of complications reported by various stratification methods

Table 2 summarizes the complication rates of several studies that stratified their patient cohort by various disease factors, patient attributes, or surgical approaches/techniques. Two reports stratified patients by body mass index (BMI). Bae et al. retrospectively divided patients into two groups and found that patients with a BMI <25 had an overall complication rate of 10.8% compared with 16.2% in patients with a BMI >25 (p = 0.545) [9]. Similarly, Gu et al. prospectively divided patients into three BMI groups and found a lower complication rate in the intermediate group (BMI: 25–30) and higher, yet not statistically significant, rates of complication in the BMI <25 and BMI >30 groups [30].

Table 2 Rates of complication by various stratification methods

StudyInstitutionTotal casesStudy designStratification method (n)Overall complication rate (%)Minor complication, 1–2 (%)Major complication, 3–5 (%)Grade 1 (%)Grade 2 (%)Grade 3 (%)Grade 4 (%)Grade 5 (%)
Bae et al. [9]Kyungpook National University, Korea111Retrospective comparativeBMI <25 (74)
BMI >25 (37)
10.8
16.2
9.4
13.5
1.4
2.7
2.7
0
6.8
13.5
1.4
2.7
0
0
0
0
Labanaris et al. [146]Prostate Center Northwest Gronau, Germany; RWTH Aachen University Hospital, Germany2000Retrospective comparativeOverall patient cohort (2000)
Age >75 yr (45)
11.4*
11.6
15.5
1.3
0.6
Ploussard et al. [33]Hospital Henri Mondor, France1009Retrospective comparativeLaparoscopic extraperitoneal radical prostatectomy (1377)
Extraperitoneal robotic prostatectomy (1009)
4
4.7
0.6
0.7
3.1
3.6
0
0
0.2
0.2
0
0.1
Zugor et al. [14]Prostate Center Northwest Gronau, Germany; RWTH Aachen University Hospital, Germany2000Retrospective comparativeOverall patient cohort (2000)
PSA >20 (147)
11.4
13.6
1.3
0.6
Zugor et al. [15]Prostate Center Northwest Gronau, Germany; RWTH Aachen University Hospital, Germany2000Retrospective comparativeOverall patient cohort (2000)
PSA <4.0 (169)
11.4
7.1
1.3
1.7
Brennhovd et al. [16]Oslo University Hospital, Norway1076Retrospective comparativeD’Amico classification low (227)
D’Amico classification intermediate (475)
D’Amico classification high (374)
1*
3
5
0
0
0
0.4
2.1
2.7
0.9
0.4
1.1
0
0.6
1.1
0
0
0.3
Froehner et al. [17]aDresden University of Technology, Germany317Retrospective comparativeOpen prostatectomy (2437)
Robotic prostatectomy (317)
29.1
33
3.7
3.2
Galfano et al. [43]Niguarda Ca’ Granda Hospital, Italy200Prospective comparativeRetzius-sparing first group (100)
Retzius-sparing second group (100)
14
11
13
9
1
2
1
2
0
0
0
0
Labanaris et al. [21]Prostate Center Northwest Gronau, Germany; RWTH Aachen University Hospital, Germany370Retrospective comparativeProstate volume >100 g (185)
Prostate volume <50 g (185)
18.9
3.2
11.1
3.2
Babaian et al. [27]University of California Irvine, USA1000Retrospective comparativeAge <69 yr(868)
Age >70 yr (129)
9.4*
15.4
1.8
3.1
0.9
1.5
6.2
10.7
0.5
0.8
0
0
Gu et al. [30]University of Oklahoma Health Sciences Center, USA218Prospective comparativeBMI <25 (36)
BMI 25–30 (115)
BMI >30 (67)
11.1
8.7
10.4
Koo et al. [31]bYonsei University College, Korea154Retrospective comparativeMen >70 yr, high risk (101)
Men >70 yr, very high risk (53)
12
15
4
4
1
2
8
11
Musser et al. [32]Memorial Sloan Kettering Cancer Center, USA651Retrospective comparativeSurgical drain (379)
No surgical drain (258)
8.7
7
2.9
4.7
5.8
2.3
2.6
4.3
0.3
0.4
0
0
Akand et al. [34]Selcuk University, Turkey; Memorial Atasehir Hospital, Turkey; Memorial Antalya Hospital, Turkey120Prospective comparativeTransperitoneal RARP (60)
Extraperitoneal RARP (60)
11.7
11.7
3.3
6.7
8.3
5
0
0
0
0
0
0
Morgan et al. [38]University of Texas Southwestern Medical Center, USA381Retrospective comparativeSingle console (185)
Dual console (196)
17.3
7.7
7
1
2.7
2.6
4.3
3.1
4.9
1
2.2
0
0
0
Sumitomo et al. [39]Aichi Medical University, Japan154Retrospective comparativeExperienced open surgeons with >30 robotic prostatectomies (90)
Experienced open surgeons with <30 robotic prostatectomies (36)
Novice open and robotic prostatectomy surgeons (28)

11.1
11.1
14.3

10
11.1
28.5
Yumioka et al. [42]Totter University, Japan150Retrospective comparativeNo prior abdominal surgery (94)
Prior abdominal surgery (56)
23.4
25

a Complications stratified as serious, overall, and individual complications, not as major or minor.

b Risk determined based on National Comprehensive Cancer Network criteria.

* Denotes statistical significance.

BMI = body mass index; PSA = prostate-specific antigen; RARP = robot-assisted radical prostatectomy.

Two publications stratified patients by age. Labanaris et al. retrospectively reviewed 2000 cases and found a significantly higher rate of minor complication in patients aged >75 yr but similarly low rates of major complications compared with the entire cohort [146]. Similarly, Babaian et al. retrospectively analyzed 1000 patients and found a significantly higher rate of overall complication in patients aged >70 yr compared with those ≤69 yr (15.4% vs 9.4%; p = 0.042) [27].

Two reports stratified patients based on risk classification. In a retrospective analysis of 1076 patients, Brennhovd et al. found a significant and progressively higher risk of overall complication with increasing D’Amico classification [16]. In contrast, Koo et al. retrospectively analyzed 154 men >70 yr and found no difference in overall complication rate between men with high-risk and very high-risk prostate cancer [31].

Two papers compared the robotic approach with previously favored approaches. Ploussard et al. retrospectively compared 1377 pure laparoscopic extraperitoneal RPs with 1009 extraperitoneal RARPs and found no difference in complication rates [33]. Likewise, Froehner et al. retrospectively compared 2437 open RPs with 317 RARPs and found no significant difference in rates of both overall (29.1% vs 33.0%; p = 0.20) and major complications (3.7% vs 3.2%; p = 0.63) [17].

3.4. Rates of specific intraoperative complications

Table 3 shows rates of specific intraoperative complications. Rates of intraoperative complications (bowel injury, neurapraxia, corneal abrasion, and ureteral injury) were typically <1%. However, Koo et al. reported a 2% incidence of rectal injury in men with high-risk and very high-risk prostate cancer [31]. In the setting of a residency training program, Morgan et al. found a similar 2.2% rate of rectal injury when utilizing a single-surgeon console; however this rate fell to 1.0% when utilizing a dual-console configuration [38]. An exception, Di Pierro et al. reported a high rate of neurapraxia (3.4%), likely secondary to positioning factors, as discussed previously [28].

Table 3 Rates of specific intraoperative complications

StudyInstitutionCasesStratification methodRectal injuryBowel injuryNeurapraxiaCorneal abrasionUreteral injury
Hung et al. [7]Taichung Veterans General Hospital, Taiwan2881.0
Ahmed et al. [8]George Washington University, USA10000.30.20.20.10.3
Dogra et al. [11]Medanta institute, India; RML Hospital, India1900.50.5
Fuller et al. [18]Schulich School of Medicine, Western University, Canada3051
Ghazi et al. [19]University of Tromso, Norway15030.10.20.5
Labanaris et al. [21]Prostate Center Northwest, Germany3700.8
Ploussard et al. [33]Hospital Henri Mondor, France10090.30.10.1
Yip et al. [13]Chinese University of Hong Kong, Hong Kong; Prince of Wales Hospital, Hong Kong; Queen Mary Hospital, Hong Kong; Princess Margaret Hospital, Hong Kong; Pamela Youde Nethersole Eastern Hospital, Hong Kong2350.4
Hashimoto et al. [20]Tokyo Medical University, Japan2001.5
Liss et al. [22]University of California Irvine, USA; Polisseni Robotic and Minimally Invasive Surgery Center, USA10000.10.50.5
Babaian et al. [27]University of California Irvine, USA1000<69 (868)
>70 (129)
0
0.8
0.6
0
0.6
0
Di Pierro et al. [28]Luzerner Kantosspital, Switzerland2333.40.9
Koo et al. [31]Yonsei University College, Korea
154
High risk (101)
Very high risk (53)

2
2




Modi et al. [37]Rutgers Cancer Institute of New Jersey, USA7510.40.1
Morgan et al. [38]University of Texas Southwestern Medical Center, USA
381
Single console (185)
Dual console (196)

2.2
1.0


0.5
0.5


Tasci et al. [40]Dr. Sadi Konuk Training and Research Hospital, Turkey; Acibadem University School of Medicine, Turkey; Umraniye Training and Research Hospital, Turkey; Ankara Ataturk Training and Research Hospital, Turkey14990.10.10.10.1
Wagenhoffer et al. [41]Klinikum Ingolstadt, Germany100010

3.5. Rates of specific postoperative complications

Table 4 lists rates of 17 distinct postoperative complications; complication rates were low with a few notable exceptions. Froehner et al. report a 30.9% lymphocele detection rate, from which however only 4.7% required intervention [17]. The authors followed the German S3 guidelines that recommend routine ultrasound lymphocele screening after surgery and intervention in the case of significant compression or thrombosis of major pelvic veins. Four series reported high rates of transfusion ranging from 6.8% to 17% [11], [17], [24], and [35]; however, each report described an “initial series” and attributed the high transfusion rate to their learning curve. Similarly, other higher than average rates of specific complications were seen in novice robotic surgeons reporting initial outcomes [25] and [39]. Mortality after RARP was extremely rare and ranged from 0% to 0.13% in reported series.

Table 4 Rates of specific postoperative complications

StudyInstitutionCasesStratification methodUrinary retentionUTIHematomaLymphoceleTransfusionDVT/PEUrine/Anastomotic leakWound complicationsIleusSBOPort site herniaMeatal/Fossa stenosisUrethral strictureBNCReoperationMIMortality
Kang et al. [12]Robert Wood Johnson Medical School, USA4980.04
Ahmed et al. [8]George Washington University, USA10001.50.21.50.50.710.10.20.10.1
Bouchier-Hayes et al. [10]Royal College of Surgeons in Ireland, Ireland1252.43.2
Dogra et al. [11]Medanta institute, India; RML Hospital, India1906.80.54.22.1
Fuller et al. [18]Schulich School of Medicine, Western University, Canada3050.32.30.33.90.63.6210.31.60.3
Ghazi et al. [19]University of Tromso, Norway15030.80.81.00.60.81.20.10.10.11.30.30.20.07
Labanaris et al., 2013Prostate Center Northwest, Germany3702.25.12.44.63.2
Ploussard et al. [33]Hospital Henri Mondor, France10093.21.41.10.22.30.40.70.30.1
Yip et al. [13]Chinese University of Hong Kong, Hong Kong; Prince of Wales Hospital, Hong Kong; Queen Mary Hospital, Hong Kong; Princess Margaret Hospital, Hong Kong; Pamela Youde Nethersole Eastern Hospital, Hong Kong2350.41.72.61.30.40.4
Brennhovd et al. [16]Oslo University Hospital, Norway1076D’Amico classification Low (227)
D’Amico classification Intermediate (475)
D’Amico classification High (374)




1.3






1
1
2




1.3
0.6
1.3




















Froehner et al. [17]Dresden University of Technology, Germany31730.98.92.52.50.70.30.3
Galfano et al. [43]Niguarda Ca’ Granda Hospital, Italy200Retzius sparing first group (100)
Retzius Sparing second group (100)

8
0



1
3

8
4

0
1





0
1




1
2


0
0
Hashimoto et al. [20]Tokyo Medical University20040.521.52.52.5
Liss et al. [22]University of California Irvine, USA; Polisseni Robotic and Minimally Invasive Surgery Center, USA10000.30.40.40.70.700.44.11.10.70.3
Sejima et al. [23]Totter University Faculty of Medicine, Japan100252
Seo do et al. [24]Eulji University, Korea10017
Stolzenburg et al. [25]University of Leipzig, Germany; University of Patras, Greece1001211
Abel et al. [26]University of Wisconsin, USA5491.3/0.5
Babaian et al. [27]University of California, Irvine, USA1000<69 (868)
>70 (129)
0.5
0
0.5
0
0.11/0.8
0.5/0.8
0.5
1.6
0.3
0.8
3.7
7.0
1
1.6
0.7
0.8
0.3
0
0
Di Pierro et al. [28]Luzerner Kantosspital, Switzerland2332.54.741.21.40.40.41.30.4
Garate et al. [35]Hospital Universitario de Caracas, Venezuela1017.92
Gu et al. [30]University of Oklahoma Health Sciences Center, USA218Normal (36)
Overweight (115)
Obese (67)

0
0.9
0

2.8
0.9
1.5


0
1.7
1.5

0
0.9
1.5

5.6
1.7
1.5




0
0.9
0



2.8
1.7
3.0



Koo et al. [31]Yonsei University College, Korea154High risk (101)
Very high risk (53)
4
4
1
2
0
2
Musser et al. [32]Memorial Sloan Kettering Cancer Center, USA651With drain (379)
Without drain (258)


0.3
0



1.6
1.2

0.8/0.4
0.8/1.2



0.5
0.8








Kumar et al. [36]University of Central Florida, USA8001.30.130.41.40.50.3
Modi et al. [37]Rutgers Cancer Institute of New Jersey, USA7510.270.130.271.5
Morgan et al. [38]University of Texas Southwestern Medical Center, USA381Single console (185)
Dual console (196)

0
2




1.6
0

0.5
0

2.7
0.5

0
1

1.6
1.0


1.6
0.5



2.2
0.5



0
0
Sumitomo et al., 2015Aichi Medical University, Japan154Expert open, >30 RARP (90)
Expert open, <30 RARP (36)
Novice open and RARP (28)





0
2.8
0




0
0
7.1


1.1
0
0






Tasci et al. [40]Dr. Sadi Konuk Training and Research Hospital, Turkey; Acibadem University School of Medicine, Turkey; Umraniye Training and Research Hospital, Turkey; Ankara Ataturk Training and Research Hospital, Turkey14990.51.20.2/0.11.40.40.60.20.20.30.10.1
Wagenhoffer et al. [41]Klinikum Ingolstadt, Ingolstadt, Germany100130

BNC = bladder neck contracture; DVT = deep venous thrombosis; MI = myocardial infarction; PE = pulmonary embolism; RARP = robot-assisted radical prostatectomy; SBO = small bowel obstruction; UTI = urinary tract infection.

3.6. Discussion

3.6.1. Intraoperative complications
3.6.1.1. Robotic malfunction

Like any technology, the robot is subject to failure and malfunction. However, given the delicate nature of surgery and the tool's proximity to the patient, the surgeon and his or her team must be able to troubleshoot any problems quickly and safely to complete the operation without compromising oncologic outcomes or causing harm to the patient. Fortunately, robotic device failures are rare occurrences. In a systematic review, Murphy et al. established that da Vinci robot device failure occurs in only 0.2–0.4% of cases [3]. In an analysis of the US Food and Drug Administration's Manufacturer and User Facility Device Experience 2009–2010 database, 565 device failures were documented, of which 50% were related to the instrument's wrist or tool tip and 31% were cautery related [44]. Although these failures occur rarely, nearly 57% of surveyed RARP surgeons reported experiencing an irrecoverable intraoperative robotic malfunction [45]. Among surgeons faced with device failure before the start of the operation, 58% rescheduled, 5% docked another robot, 19% performed open RP, and 15% proceeded with a straight laparoscopic approach [45]. Conversely, among those surgeons experiencing device failure before completion of the urethrovesical anastomosis, 62% converted to straight laparoscopy and 38% converted to open surgery [45].

This survey demonstrates that although it is statistically unlikely to experience device failure, a majority of both high- and low-volume RARP surgeons have experienced device failure. Therefore, although all steps should be taken to minimize such an event, the surgeon must always be prepared should device malfunction occur. First, surgeons should be familiar with all components of the device and be appropriately credentialed prior to performing robot-assisted surgery independently [44] and [45]. Second, systems and checks should be implemented to ensure routine maintenance on all robotic systems, and surgical support staff should evaluate all device components to ensure proper functioning at the onset of each case, prior to the induction of anesthesia [44] and [45]. Finally, patients must be aware of the rare possibility of device malfunction and understand the need to adopt an alternative surgical approach [44] and [45].

Prevention point: Systems should be implemented to ensure routine maintenance of all robotic systems; all device components should be evaluated to ensure proper functioning at the onset of each case, prior to the induction of anesthesia.

Regarding laparoscopic access, a recent systematic review of complications after RARP reported a low incidence of bowel and vascular injuries, 0.07–0.09% and 0.03–0.2%, respectively [46]. Techniques for access include Veress needle placement, direct trocar insertion, minilaparotomy [47] or Hassan technique [48], and optical trocar placement [49]. There is wide variation among surgeon preference, yet the available evidence does not demonstrate a superior technique [50]. Thus surgeons should be comfortable with multiple techniques [46]. Some prefer the optical trocar in obese patients because minilaparotomy can be difficult, and other available techniques require blind placement [49]; however, Veress needle access has been shown to be safe in obese patients [51]. In patients with prior abdominal surgery, risk factors for intra-abdominal adhesions, or umbilical hernia, either the Hassan technique or placement of the Veress needle in the left upper quadrant may be preferable [46], [52], and [53]. Confirmation that the trocar is in the correct position should be confirmed by aspiration and then instillation of saline.

Extra caution should be exercised when obtaining access in patients with history of mesh placement for abdominal wall herniorrhaphy given the increased risk of subsequent bowel adhesion. Although these patients can still undergo successful RARP, the surgeon should expect prolonged console times given the need for a more tedious dissection [54].

Care must also be taken to avoid placing secondary trocars through abdominal wall vasculature. This can be accomplished by dimming operating room lighting and using the laparoscopic camera to transilluminate the abdominal wall [46]. Vascular injuries during access should be managed based on severity. Small nonexpanding hematomas may be outlined with clips and later reassessed at pneumoperitoneum of 5 mm Hg, and if the hematoma expands, it should be explored [46].

Prevention point: Surgeons should thoroughly review the patient's surgical history and physical examination to choose the best method to obtain access.

3.6.1.3. Nerve injury, rhabdomyolysis, pressure injury, and lower extremity compartment syndrome

Pressure- and positioning-related wounds have been variably reported, with the most thorough assessment performed by Di Pierro and colleagues demonstrating a rate of severe pressure ulcers as high as 3% [28]. Similarly, Mattei et al. found a 5% incidence of severe pressure wounds, with the gluteal region most commonly involved [55]. Pressure-related injuries were largely related to longer operative times and nonmodifiable factors including patient comorbidity and Trendelenburg positioning [28] and [55].

In a literature review of brachial plexus injury during laparoscopic/robotic surgery in the Trendelenburg position, steep Trendelenburg positioning, arms extended at ≥90°, and use of shoulder braces are associated with brachial plexus injury [56] and [57]. Although these injuries are largely self-limited, patients with brachial plexus injury should be referred to physical therapy and treated with nonsteroidal anti-inflammatory medications or neuropathic agents (gabapentin or topiramate) [56] and [57]. Prevention includes limiting operative time and proper patient positioning. Arms should be tucked at the sides with the palms facing the thigh, and arm boards and shoulder braces should be avoided [56]. To implement proper positioning, many centers now utilize disposable foam padding along with straps and strong tape (Fig. 2).

gr2

Fig. 2 Patient padding and positioning during robot-assisted radical prostatectomy performed via robotic side docking. (A) Arm placed in egg crate with palm facing body and thumb pointing up; (B) arms tucked with draw sheet; (C) heels padded in egg crate; (D) pillow placed under knees; (E) egg crate placed diagonally across shoulder and contralateral elbow and secured with heavy tape and reinforced with safety belts to prevent movement in steep Trendelenburg position; (F) later view of complete positioning.

Pridgeon et al. performed a multicenter retrospective review of 3110 RARP cases and identified nine patients who developed lower extremity compartment syndrome [58]. Risk factors included obesity, prolonged console time (>4 h), and a history of peripheral vascular disease. Prevention requires proper positioning, with the heel supporting most of the pressure and adequate space between the upper calf and the stirrup (when in lithotomy). Early recognition is critical for successful treatment and characterized by the 6 Ps (pain, pressure, paresthesia, pallor, paralysis, and pulselessness) [58].

Prevention point: Neurapraxia, pressure injury, and compartment syndrome can be avoided with careful attention to proper patient positioning practices.

3.6.1.4. Ocular complications

In our review, five papers documented corneal abrasions with a rate between 0.1% and 0.6% [8], [19], [22], [27], and [37]. Although occurring at a low rate, corneal abrasion can cause significant discomfort for the patient; use of a transparent occlusive eye dressing rather than tape was demonstrated to eliminate this complication in a single-institution retrospective review [59]. Although no studies of corneal abrasion following RARP examined predictors, a study of 91 064 patients undergoing nonocular surgeries at a major academic center by Lichter et al. described an incidence of 0.13%. Their anesthesia-led protocol for management of postoperative corneal abrasions included stepwise treatment with artificial tears, followed by erythromycin ointment if not effective [60]. With implementation of their protocol, all patients had resolution of their symptoms by postoperative day 1. Patients who experienced corneal abrasions had longer operative times and were older. Prolonged case duration (8–10 h) has been associated with corneal abrasion; however, steep Trendelenburg has not [61], [62], and [63]. Steep Trendelenburg positioning during RARP has been shown to increase intraocular pressures significantly and occasionally results in significant yet temporary visual field defects. Thus a theoretical risk of optic nerve hypoperfusion exists, and preoperative ophthalmologic evaluation can be considered in patients with glaucoma and diabetes mellitus at baseline risk of optic nerve injury [64].

Prevention point: Consider using transparent occlusive eye dressings rather than taping the eyes shut to minimize risk of corneal abrasions.

3.6.1.5. Ureteral injury

Our literature review indicates that ureteral injury occurs in 0.06–0.9% of cases. If ureteral injury is from sharp dissection and noted intraoperatively, it may be primarily repaired. If cautery injury is noted, a retrograde ureteral stent should be placed [46]. These injuries are frequently not recognized intraoperatively, necessitating delayed repair. Ureteral injury commonly occurs during adhesiolysis, bladder neck dissection, vesicourethral anastomosis, or lymphadenectomy, and thus the surgeon should be particularly vigilant about the ureter during these steps [65]. Management depends on the location and severity of injury and may require ureteroneocystostomy [46] and [65]. Risk factors may include prior pelvic surgery, prior transurethral resection of the prostate (TURP), salvage RP, and extensive adhesiolysis [65].

3.6.1.6. Rectal injury

Rectal injury is a rare complication during RARP but is associated with significant morbidity, especially if not recognized intraoperatively and repaired. Wedmid et al. reviewed 6650 cases from 11 different surgeons and found an overall incidence of 0.17% [66]. Overall, 73% of cases were identified intraoperatively and managed with a two- to three-layer closure depending on surgeon preference. Three patients had injuries that were not recognized intraoperatively and presented with rectovesical fistula between 2 d and 6 wk later. These patients required ileostomy diversion and delayed repair. Kheterpal et al. published a review of 4400 cases with a 0.2% incidence of rectal injury [67]. All 10 patients in this series were recognized intraoperatively and repaired with 2-0 polyglactin suture in a two-layer fashion. In both series, no patient characteristics predicted rectal injury, and extended catheterization along with watertight urethrovesical anastomosis in cases of rectal injury were emphasized. In addition to a multilayered closure, several authors have reported using an omental flap to reinforce the rectal repair [68] and [69].

Many urologists have now moved away from full bowel prep given the rarity of bowel injury and the evidence of safety with less aggressive bowel prep [70] and [71]. Nonetheless, more aggressive bowel prep may be warranted in men at increased risk of rectal injury, such as men with a history of TURP [71] and [72]. When possible, patients should wait at least 4–6 wk after prostate biopsy before undergoing RARP because acute prostatic inflammation after biopsy may obliterate surgical planes and increase the risk of rectal injury [73].

Prevention point: Wait at least 4–6 wk after prostate biopsy before performing robot-assisted radical prostatectomy to allow time for postbiopsy inflammation to subside.

3.6.2. Postoperative complications
3.6.2.1. Small bowel obstruction

Rates of small bowel obstruction (SBO) ranged from 0.1% to 4.2% in the current review. The literature provides little insight into the various causes of SBO post RARP, yet SBOs are likely sequelae of unrecognized intraoperative bowel injury. In a rare instance of SBO 3 mo post RARP, an unhinged Hem-o-Lok vascular clip (Weck; Teleflex Medical, Durham, NC, USA) was the causal agent [74]. A high index of suspicion and early recognition of a possible bowel complication is crucial because laparoscopic bowel injuries may present in an atypical fashion [75]. In the absence of signs/symptoms of peritonitis or bowel strangulation, nonoperative management with tube decompression may be trialed; however, if there is no improvement by day 3–5 of conservative management, the patient should be simulated with a water-soluble contrast medium or evaluated for surgery [76] and [77].

3.6.2.2. Pelvic hematoma

In the current review, rates of hematoma ranged from 0.9% to 2.4%. Pelvic hematomas commonly develop in the prostatic resection bed between the rectum and bladder; when sizable, patients present with tenesmus, pelvic pain, hematuria, and in severe cases symptomatic hypovolemia secondary to acute blood loss anemia [78]. Large pelvic hematomas can result in disruption of the urethrovesical anastomosis (UVA) and result in delayed return of normal micturition. Prevention of hematoma primarily depends on meticulous dissection and hemostasis technique [79].

Kirby et al. have suggested several tips to minimize hematoma formation: clipping the prostatic pedicle to prevent internal iliac bleeding; utilizing the Rocco suture [80] to minimize the potential space for hematoma formation within the prostatic bed; and finally, spraying a fibrin sealant along the neurovascular bundles and anterior rectal wall prior to the Rocco suture can be considered in higher risk patients [78]. If the patient is hemodynamically unstable, operative exploration is essential to evacuate the hematoma and to identify and repair the origin of bleeding. Kirby et al. successfully managed this complication robotically by evacuating the hematoma and reconstructing the UVA [78]. In most cases, however, hematomas can be managed conservatively with prolonged catheterization and subsequent cystogram to ensure an intact anastomosis [78].

Prevention point: Pelvic hematoma is prevented by meticulous dissection and hemostasis but can be further minimized by clipping the prostatic pedicle, spraying fibrin sealant along neurovascular bundles, and utilizing the Rocco suture.

3.6.2.3. Lymphocele

The reported rate of lymphocele after RARP largely depends on the method of detection and ranges from 0.1% to 30.9%. A recent systematic review found a 0–8% incidence of symptomatic pelvic lymphocele after RARP with a subsequent 0–5% intervention rate [81]. Lymphoceles are thought to occur secondary to inadequate ligation of lymph channels after pelvic lymph node dissection (PLND) and the inability of collaterals to compensate adequately for the disrupted channels [82] and [83]. Despite meticulous dissection and ligation, lymphatic channels can often leak fluid for up to 48 h and result in a pelvic fluid collection with subsequent development of a hard fibrous pseudocapsule [84] and [85]. Lymphoceles become problematic when infection develops or when significant pressure is exerted on surrounding structures. Patients can present with abdominal and leg pain, lower extremity edema, urinary frequency, constipation, ileus, or fever and leukocytosis [86] and [87]. Although there is no clear threshold size at which a lymphocele becomes problematic, larger lymphoceles exert greater pressure on adjacent structures and thus increasing size results in increased potential morbidity [88]. Although there is clear oncologic benefit to an extended pelvic node dissection (ePLND) [89], [90], [91], and [92], it has not been fully elucidated if ePLND imposes a greater risk of lymphocele compared with standard PLND. Therefore, given similar rates of overall complications and interventions, ePLND should be performed given superior oncologic control [88]. No definitive link has been found between the extent of lymph node dissection and lymphocele formation, but it is likely that the etiology of increased lymphocele formation in node-positive patients is influenced by surgeon suspicion and consequent aggressive dissection rather than intrinsic factors related to malignant involvement of the nodes [88] and [93].

Pharmacologic prophylaxis for deep venous thrombosis (DVT) was previously implicated in lymphocele formation due to possible impairment of lymph coagulative properties; however, no definitive consensus exists, and the benefit of treatment appears to outweigh the possible harms [88], [94], and [95]. Similarly, routine pelvic drain placement has not demonstrated decreased lymphocele formation in RARP plus PLND patients [88], [96], [97], and [98].

Several authors have examined the effect of energy source on subsequent lymphocele formation, and although the overall quality of the evidence is low, bipolar energy and the judicious use of clips has been associated with lower lymphocele rates [88], [99], and [100].

Both symptomatic and asymptomatic lymphoceles are likely to resolve without intervention; however, several treatment options exist if intervention is required [88]. Percutaneous drain placement is the most common initial treatment, but in situations where high output persists despite drainage, a sclerosing agent can be administered. Percutaneous drainage, with optional sclerosis, has been used successfully to resolve 70–100% of symptomatic lymphoceles [101], [102], [103], [104], [105], [106], and [107]. In lymphoceles refractory to percutaneous drainage, minimally invasive marsupialization of the lymphocele cavity was shown to be a safe and definitive intervention [108].

Prevention point: Consider the use of bipolar energy and judicious use of clips when performing lymph node dissection to minimize lymphocele formation.

3.6.2.4. Deep venous thrombosis and pulmonary embolism

Rates of thromboembolic complication were low in our systematic review ranging from 0.2% to 2.5% [26], [94], [109], and [110]. Nonetheless, similar to lymphocele, the rate of venous thromboembolism (VTE) largely depends on the mechanism of detection. In a recent Chinese study, 109 consecutive patients underwent RARP (utilizing intermittent pneumatic compression devices) and bilateral lower limb Doppler ultrasonographic examination on postoperative day 3, and a high (16.9%) incidence of DVT was found [111]. Only one patient developed an above-knee DVT, and no patient developed a DVT-associated complication [111].

Risk factors of VTE include older age, elevated BMI, history of prior DVT, current tobacco smoking, and larger prostate volume [26], [110], [111], and [112]. Surgical factors predictive of thromboembolic complications included lymph node dissection, prolonged operative time, need for blood transfusion, longer hospital stay, and reexploration [26], [110], [111], and [112]. Routine use of subcutaneous heparin for VTE prophylaxis has not been shown effective in preventing thromboembolic or increasing bleeding events [94], [109], and [110]. Although all patients should receive intermittent pneumatic compression and be encouraged to ambulate early, current evidence only supports use of perioperative prophylactic anticoagulation in patients at high risk of a thromboembolic event [94], [109], [110], and [113]. For these RARP patients at high risk of VTE and without a major bleeding risk, the guidelines recommend extended-duration postoperative low-molecular-weight heparin prophylaxis for a total of 4 wk [111].

Lower extremity DVT may be suspected based on unilateral lower extremity swelling or pain; however, objective testing is recommended given the inability to make a reliable clinical diagnosis [114]. For patients with low or moderate pretest probability, a highly sensitive D-dimer should be followed by compression ultrasound of the proximal veins; patients with high pretest probability should proceed directly to proximal compression ultrasound [114]. Parenteral anticoagulation should commence once diagnosis of an acute DVT of the lower extremity has been made or immediately if there is high clinical suspicion [115].

Prevention point: Use of pneumatic compression devices and early ambulation should be encouraged for all robot-assisted radical prostatectomy patients to prevent deep venous thrombosis.

3.6.2.5. Urine leak

Consistent with prior reports, rates of urethrovesical anastomotic leak (UVAL) ranged from 0.5% to 5% in our review [116] and [117]. Prior research has demonstrated that rates of UVAL are highest in the first 7–10 d postoperatively and decreases thereafter [116], [118], and [119]. Both patient factors (obesity, large prostate, and prior prostatic surgery) and technical factors (excessive bleeding, surgeon learning curve, urethral stump length, and integrity of anastomosis during bladder distention) have been implicated as possible risk factors for UVAL [116]. Diagnosis is often based on high drain output, elevated drain creatinine, and symptoms of uroperitoneum. Conventional cystography, computed tomography (CT) cystography, transrectal ultrasound, and a technetium-mercaptoacetyltriglycine-3 renogram have been utilized to diagnose and evaluate UVAL [116], [120], and [121].

In many situations, UVAL is discovered during cystography prior to catheter removal [117]. For most of these leaks, replacement of the catheter alleviates the acute abdominal symptoms, and prolonged catheterization allows for complete resolution of the UVAL. At 3 wk, most leaks will have closed; however, repeat cystography prior to catheter removal is recommended [116], [122], [123], [124], and [125]. Surgical drains should also be taken off suction, and if no drain was placed intraoperatively or if a urinoma collects, a percutaneous drain can be placed. If these measures fail, nephrostomy placement or reoperation should be considered to repair the UVA [116]. Prevention relies on proper training and execution of anastomotic principles; however, utilization of a fenestrated catheter, fibrin sealants, and oxidized cellulose sponges facilitate a watertight UVA [126], [127], and [128]. Fortunately, although UVAL can be troublesome to manage, two retrospective analyses found no long-term impact on erectile function, bladder neck contracture (BNC), or continence [129] and [130].

3.6.2.6. Port-site hernia

In our current review, incidence of port-site hernia ranged from 0% to 7% in some specific cohorts; prior reports reported an incidence ranging from 0.4% to 16.7% [12], [131], [132], [133], and [134]. Port-site hernias may be difficult to detect clinically, but a single-institution retrospective review of 104 patients undergoing robot-assisted urologic surgery (38 RARP patients) found a 6.7% incidence rate of CT-detected clinically occult hernias [133]. Most of them were located at extraction sites or larger port-site locations; thus increased vigilance is required when closing the fascia at these sites [133].

Concordantly, multiple studies have consistently identified larger prostate size as a primary predictor of incisional hernia [131], [132], and [133]. Proposed methods to diminish the incidence of port-site hernia include closing fascia with nonabsorbable suture in an interrupted fashion rather than a running suture line and making transverse port-site incisions rather than traditional vertical incisions [131] and [134]. After controlling for baseline factors, Beck et al. found that vertical incision resulted in an 11-fold increased hazard of incisional hernia compared with a transverse incision [131].

Prevention point: In patients with larger prostates, consider utilizing transverse incisions and interrupted closure of the midline fascia to reduce incidence of incisional hernia.

3.6.2.7. Bladder neck contracture

BNC following prostatectomy often presents with obstructive voiding symptoms such as a weak urinary stream and incontinence [135]. Consistent with prior reports, our current review demonstrates an incidence of BNC ranging from 0.3% to 3.2% [135], [136], [137], [138], [139], and [140]. Symptoms of BNC often appear early, with many patients reporting symptoms around the fifth month postoperatively [135], [136], and [139]. Although the exact etiology of BNC is unknown, several inciting factors have been demonstrated including increased blood loss [135], Hem-o-Lok clip migration [135] and [141], length of time before drain removal [137] and [140], and increased operative time [139]. Several authors have implicated Hem-o-Lok clip migration as a cause of BNC, and thus surgeons should minimize clip usage on tissues surrounding the UVA and should take care to remove any loose clips [135], [141], [142], [143], and [144].

A recent prospective randomized controlled trial of 62 patients equally randomized to urethral catheterization versus suprapubic catheter (SPT) drainage found a reduced incidence of BNC in the SPT cohort [145]. Thus BNC can be limited with prudent Hem-o-Lok clip utilization and SPT drainage, and notably, most BNCs can been managed successfully with endoscopic interventions [135].

Prevention point: Avoid Hem-o-Lok clip use on tissues surrounding the urethrovesical anastomosis and consider suprapubic catheter bladder drainage to minimize risk for bladder neck contracture.

4. Conclusions

The RARP technique has continued to gain in popularity and utilization. Despite the rapid adoption of this technique by surgeons globally, overall complication rates remain low and have been demonstrated to decrease as surgeons move along the learning curve. RARP is a successful operation in that it is reproducible and safe. Many of the complications experienced during and after RARP can be mitigated and prevented by experience and the implementation of particular protocols, as described in this review (Supplementary Table 1). Future efforts should focus on prospective studies and randomized studies attempting to better elucidate methods of avoiding perioperative RARP complications.


Author contributions: Daniel Pucheril 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: Schlomm, Sammon, Montorsi, Bauer.

Acquisition of data: Pucheril, Campbell.

Analysis and interpretation of data: Sammon, Pucheril, Campbell.

Drafting of the manuscript: Pucheril, Campbell, Bauer, Montorsi, Sammon, Schlomm.

Critical revision of the manuscript for important intellectual content: Bauer, Montorsi, Schlomm.

Statistical analysis: Pucheril, Campbell.

Obtaining funding: None.

Administrative, technical, or material support: None.

Supervision: Bauer, Montorsi, Sammon, Schlomm.

Other (specify): None.

Financial disclosures: Daniel Pucheril 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.

Appendix A. Supplementary data

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Footnotes

a VUI Center for Outcomes Research, Analytics and Evaluation, Detroit, MI, USA

b Department of Urology, Ludwig Maximilian University, Munich, Germany

c Department of Urology, University Vita-Salute San Raffaele, Milan, Italy

d Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Corresponding author. Vattikuti Urology Institute, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48128, USA. Tel. +1 313 916 2062.

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