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Review – Bladder Cancer

Critical Review of Outcomes from Radical Cystectomy: Can Complications from Radical Cystectomy Be Reduced by Surgical Volume and Robotic Surgery?

By: Marco Moschinia , Giuseppe Simoneb, Arnulf Stenzlc, Inderbir S. Gilld and James Cattoe

EU Focus, Volume 2 Issue 1, April 2016, Pages 19-29

Published online: 01 April 2016

Keywords: Bladder cancer, Radical cystectomy, Complications, Surgeon volume, Surgical volume, Perioperative outcomes, Robot-assisted radical cystectomy

Abstract Full Text Full Text PDF (639 KB)

Abstract

Context

Radical cystectomy (RC) is a highly complex procedure with multiple risks for perioperative complications.

Objective

We reviewed the literature to report perioperative outcomes and the incidence of complications in contemporary RC series. We focused on the potential impact of surgical approach and surgeon volume on these outcomes.

Evidence acquisition

A systematic literature search was performed in December 2015 using the Medline, Embase, and Web of Science databases for articles published in English between 2005 and 2015. The search strategy included the terms complications, cystectomy, robotic assisted radical cystectomy, and surgical volume, alone or in combination. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed.

Evidence synthesis

Our searches retrieved 49 papers. Open RC (ORC) and robot-assisted RC (RARC) are morbid procedures with consistent risk of perioperative complications (mean weighted incidence: 48.7%; range: 27.0–72.5%). Higher hospital and surgeon volumes were associated with reduced risks of perioperative complications. Prior robotic expertise in radical prostatectomy showed a beneficial protective risk on development of complications after RARC. Surgical volume appears to be a good predictor of safety in ORC and RARC. RARC is associated with reduced estimated blood loss and lower perioperative transfusion rates compared with ORC. Further evidence is needed to support the reproducibility of intracorporeal diversion during RARC, beyond large tertiary referral centers. Several strategies have been demonstrated to be effective for reducing the risk of incurring perioperative complications and should be pursued by physicians.

Conclusions

Despite improvements in quality of care, RC remains a challenging procedure with high morbidity, regardless of surgical approach. RARC is a safe procedure with potential advantages in terms of reduced blood loss and transfusion rates. Surgical volume appears to be related to the improvement of perioperative outcomes and complications.

Patient summary

Radical cystectomy is a challenging and morbid procedure. The robotic approach has gained popularity and proved to be safe and effective in tertiary referral centers, although further studies are needed to confirm its wide reproducibility. Centers with higher surgical volume have lower incidence of perioperative complications.

Take Home Message

Radical cystectomy is a challenging and morbid procedure. The robotic approach has gained popularity and proved to be safe and effective in tertiary referral centers, although further studies are needed to confirm its wide reproducibility. Centers with higher surgical volume have lower incidence of perioperative complications.

Keywords: Bladder cancer, Radical cystectomy, Complications, Surgeon volume, Surgical volume, Perioperative outcomes, Robot-assisted radical cystectomy.

1. Introduction

Radical cystectomy (RC) with pelvic lymph node dissection represents the current standard of care for the treatment of muscle-invasive and recurrent high-risk non–muscle-invasive bladder cancer [1]. RC is a morbid procedure [2] and [3] that has improved in recent years through changes in patient selection [4], anesthetic and surgical refinements [5], and perioperative care [6] and through the concentration of this surgery at larger volume centers [7]. Although open RC (ORC) remains the most common surgical approach, minimally invasive techniques, including robot-assisted RC (RARC), have gained in popularity [5] and [8].

ORC and RARC are complex procedures performed mostly in older patients with smoking-related comorbidities. As such, it is likely that surgeon and surgical team experience and hospital volume affect patient outcomes through the prevention and expeditious management of perioperative complications [9]. Given recent refinements in RC practice, there is a need to detail contemporary outcomes and to evaluate the impact of procedural volume and surgical route on these events. In this systematic review, we summarized contemporary rates of RC complications and discussed the impact of surgical volume and RC route on these risks.

2. Evidence acquisition

A literature review was performed in December 2015 using the Medline, Embase, and Web of Science databases with the terms complications, cystectomy, robotic assisted radical cystectomy, and surgical volume. We limited our search to large population-based retrospective studies and prospective investigations published between January 2005 and December 2015 in an attempt to select contemporary and reproducible data sets. M.M and G.S. read and reviewed all abstracts and full-text articles in depth. All authors approved the selected articles that met the inclusion criteria indicated by the patient population, intervention and exposure, comparison, outcome, and study design (PICOS) approach. Cited references from selected articles were also used to identify manuscripts not found by the initial search. We selected articles published in the English language reporting outcomes in >100 patients. Case reports, meeting abstracts, editorials and letters, and series with <100 patients were excluded. The primary outcome was to report complications after RC. Secondary outcomes were to assess the potential impact of surgical approaches and volumes on the risk of developing complications in patients treated with RC. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines [10].

3. Evidence synthesis

A total of 49 studies met our inclusion criteria (Fig. 1). These studies confirmed that RC can be a morbid procedure, with complication rates ranging between 27% and 73% depending on the definition (Table 1 and Table 2). In general, except for transfusion and blood loss, the reported complication rates were broadly similar for ORC and RARC. The quality of the included data sets varied. One of the first steps in preventing complications is the accurate documentation of outcomes [3]. The best reports included those with prospectively collected outcomes using standardized reporting criteria. Although generic classifications (eg, Clavien-Dindo outcome [11]) may require adaptation for surgery [12], they are not fully applicable to RC. Shabsigh et al reported prospectively refined standardized reporting criteria specific to RC [13]. Given their specificity, these criteria could be seen as the current gold standard criteria for outcomes from this procedure.

gr1

Fig. 1 Flow diagram of the search results.

Table 1 Selected series of radical cystectomy with reported perioperative complications

Konety et al., 2006 [14]Novotny et al., 2007 [15]Nieuwenhuijzen et al., 2008 [16]Lowrance et al., 2008 [17]Shabsigh et al., 2009 [13]Novara et al., 2009 [18]Ramani et al., 2009 [19]Takada et al., 2012 [20]Roghmann et al., 2013 [21]Schiavina et al., 2013 [22]De Nunzio et al., 2013 [23]Lavallée et al., 2014 [24]Gandaglia et al., 2014 [25]Cantiello et al., 2014 [26]
Patients, n6577516281553114235884692853540446723033760346
Study period, yr1998–20021993–20051990–20052000–20051995–20052002–20061970–20051997–20102003–20121995–20092011–20122006–20122000–20092008–2012
CenterMulticentricDresden, GermanyThe Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The NetherlandsVanderbilt University Medical Center, Nashville, TN, USAMemorial Sloan Kettering Cancer Center, New York, NY, USAUrology Clinic, University of Padua, Padua, ItalyDepartment of Urology, The Christie, Manchester, UKHokkaido University Hospital- Sapporo, JapanMarienhospital Ruhr-University Bochum, Herne, GermanyDepartment of Urology, University of Bologna, Bologna, ItalyMulticentricMulticentricMulticentricMulticentric
Postoperative complications, %28.4274445.4644935.5685651.764.755.372.566.8
Operating time, min366384300393370272
Blood loss, ml120860010006001300750
Transfusion rate, %2.338661514.240.046.733.5
Mortality at 30 d, %2.60.82.81.71.53.02.98.2
Medical, %
DVT, PE0.54.7, 1.71.4, 2.52.5, 1.25.3, 3.244.1, 2.80.1, 0.22.2, 2.11.2, 1.90.24.00.3
Septicemia1.49.60.96.61.51.32.20.49.7
Respiratory3.81.68.92.87.45215.92.644.12.3
Cardiac4.10.42.142.342.50.68.27.60.82.65.62.6
Gastrointestinal16.11.73.431510.715
UTI12.8109.98.421.613.49.539.49.5
Pyelonephritis2.512.40.6
Metabolic0.70.720.315.63.7
Neurologic1.40.50.522.70.60.3
Surgical, %
Reintervention6.2231018.2
Enteroanastomosis leak0.70.90.920.7
Subileus (paralytic)3.92.8221685.43.2
Wound infection87.59.34.518.73.08.44.0
Wound dehiscence4.350.54.654.34.17.74.73.2
Pelvic lymphocele5.40.51.30.72.70.61.4
Urine leak2.91.12.613.93.65.04.73.5
Fistula0.50.40.52.2

DVT = deep venous thrombosis; PE = pulmonary embolism; UTI = urinary tract infection.

Table 2 Selected series of radical cystectomy in elderly patients with reported perioperative complications

ReferenceCasesOutcomesResultsConclusion
Clark et al., 2005 [34]1054, ORCEarly and late complicationsAge 60 yr: early 24.0%, late 36.0%
Age 60–69 yr: early 25.0%, late 30.0%
Age 70–79 yr: early 37.0%, late 22.0%
Age ≥80 yr: early 30.0%, late 14.0%
Elderly patients had similar complication rates.
Fairey et al., 2008 [35]314, ORCEarly and major postoperative complicationsAge <60 yr: early 38.4%, major 25.6%
Age 60–69 yr: early 47.5%, major 20.8%
Age 70–79 yr: early 51.8%, major 29.1%
Age ≥80 yr: early 41.2%, major 17.6%
Elderly patients had similar complication rates.
Shabsigh et al., 2009 [13]1142, ORCMultivariable logistic regression predicting any and grade 3–5 complicationsAny complication: OR 1.07 (p = 0.08)
Grade 3–5: OR 1.12 (p ≤ 0.04)
Age is an independent predictor of grade 3–5 complications.
Boström et al., 2009 [36]258, ORCIn-hospital, early and total major complicationsAge <65 yr: 4%, 4%, 8%
Age ≥65 yr: 11%, 3%, 14%
Increased age was related to increase in in-hospital but not early or total major complications.
Johar et al., 2013 [37]939, RARCAny and
grade 3–5 complications
Univariable analyses:
Age: any grade, OR 1.27 (p = 0.001); grade 3–5, OR 1.23 (p = 0.02)

Multivariable analyses
Age: any grade, OR 1.34 (p < 0.001); grade 3–5, OR 1.39 (p = 0.002)
Increased age was related to increase in overall and high-grade complications.

OR = odds ratio; ORC = open radical cystectomy; RARC = robotic assisted radical cystectomy.

3.1. Complications and open radical cystectomy

Table 1 summarizes postoperative complications, operative time, estimated blood loss, transfusion rate, and mortality at 30 d for ORC. Perioperative complications are stratified as medical and surgical, according to impact. We included a selection of ORC surgical series published in the past 10 yr [2], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], and [26]. Weighted mean operative time was 363 min (range: 272–393 min) for patients treated with ORC. Overall mean blood loss was 980 ml (range: 600–1208 ml), and transfusion rates ranged from 2.3% to 66% (median weighted transfusion rate: 40.0%). The average 30-d mortality rate was 3.8% (range: 0.8–8.2%), and the postoperative weighted complication rate was 48.7% (range: 27.0–72.5%). Similar complication rates were observed in patients treated with low anterior resection for rectal cancer (range: 31–40%). Deep vein thrombosis and pulmonary embolism occurred in 1.9% (range: 0.2–4.7%) and 2.0% (range: 0.2–3.2%) of patients, respectively. These rates are comparable to those for other major surgeries [27] and [28] and can be successfully reduced with a combination of strategies included in the UK National Institute for Health and Care Excellence guidelines: low-molecular-weight heparin, compression stockings, pneumatic compression stockings, early mobilization, and fluid resuscitation [29]. Overall, 13.2% (range 1–44.1%), 3.8% (range: 0.4–8.2%), and 13.1% (range: 3–16.1%) of patients experienced respiratory, cardiac, and gastrointestinal complications, respectively. Preoperative anesthetic assessment with the correction of modifiable medical disease should be pursued by physicians to reduce these complications [30].

Urinary tract infection (UTI) and pyelonephritis were recorded in 21.3% (range: 8.4–39.4%) and 3.8% (range: 0.6–2.5%), respectively. Increased body mass index is associated with an increase in the risk of infection and dehiscence after surgery [31]. Consequently, only experienced urologists should perform RC in obese patients due to the increased risk of bleeding, UTI, and other types of infections [3]. The average reintervention rate was 7.8% (range: 2–18.2%). Interventions included surgical wound dehiscence with resuture of incision, small bowel obstruction, refashioned stoma, and laparotomy due to bowel, urinary, or vessels leaks. Wound infection, wound dehiscence, and pelvic lymphocele were recorded in 7.2% (range: 3–18.7%), 4.1% (range: 0.5–7.7%), and 1.7% (range: 0.5–5.4%), respectively. The wound infection rate is comparable to that for open colorectal surgery and may be improved by the application of multiple steps [32]. The incidence of pelvic lymphocele in radical prostatectomy patients is similar to that in RC patients but is strongly related to the number of nodes removed and the administration of low-molecular-weight heparin [33]. A selection of reports assessing complications after RC in elderly patients is reported in Table 2. In context, although in some series, no differences were found in the prediction of complications considering age at surgery [34] and [35], some authors found that older patients were more inclined to have higher grade complications [2] or in-hospital complications [36]. Moreover, Johar et al described an increased risk for older patients of both overall and high-grade (grade 3–5) complications for patients treated with RARC [37]. Previous reports found similar outcomes, especially in high-volume centers [38]. Some authors suggested that perioperative [39] and, specifically, intraoperative [40] and [41] transfusion may be associated with worse survival outcomes after RC. This effect could be explained as an indirect marker of advanced pathologic stage or as a direct effect of immunologic suppression mediated by the transfusion itself [40].

3.2. Complications and robotic assisted radical cystectomy

Table 3 summarizes the postoperative complications, operative time, estimated blood loss, transfusion rate, and mortality at 30 d in patients treated with RARC. The weighted mean operative time was 393 min (range: 276–577 min) for patients undergoing RARC with extracorporeal conduct diversion [37], [42], [43], [44], [45], [46], and [47], The mean estimated blood loss was 460 ml (range: 200–526 ml), and 15% of patients (range: 15–17%) underwent intraoperative transfusion. Intraoperative and overall complications were reported in 3.0% (range: 2–4%) and 38.4% (range: 27–42%), respectively. Median length of stay was 7.9 d (range: 4.9–18.4 d), and 19.4% of patients (range: 11–21%) experienced readmission at 30 d after discharge.

Table 3 Selected series of robotic assisted radical cystectomy series with reported perioperative complications stratified according urinary diversion type

StudyInstitutionCasesOperative time, medianBlood loss, mlTransfusion, %Intraoperative complications, %Overall, complications, %Length of stay, dReadmission, %Clavien 3b–4, %
Mainly extracorporeal conduit diversion
Pruthi et al., 2010 [42]University of North Carolina, Chapel Hill, NC, USA1002762502364.9118
Kang et al., 2010 [43]Multicenter10455452642718.42
Hayn et al., 2010 [44]Multicenter482385408
Hayn et al., 2011 [45]Roswell Park Cancer Institute, Buffalo, NY, USA15657740016408212
Smith et al., 2012 [46]Multicenter2272912003050
Johar et al., 2013 [37]Multicenter93958015418201.3
Xylinas et al., 2013 [47]Weill Cornell Medical Center, New York, NY, USA175360400174275
Mainly extracorporeal continent diversion
Yuh et al., 2012 [48]City of Hope Comprehensive Cancer Center, Duarte, CA, USA196432400448094
Nazmy et al., 2014 [49]City of Hope Comprehensive Cancer Center, Duarte, CA, USA209775
Mainly intracorporeal conduit diversion
Azzouni et al., 2013 [50]Roswell Park Cancer Institute, Buffalo, NY, USA100352300106391613
Koupparis et al., 2015 [51]North Bristol NHS Trust, Southmead Hospital, Bristol, UK10219313
Mainly intracorporeal continent diversion
Desai et al., 2014 [52]Multicenter1324564604.5478
Extracorporeal vs intracorporeal
Ahmed et al., 2014 [53]589 EIC
198 C
87 IIC
91 C
49

41
8

9
15

5
ORC vs RARC
Ng et al., 2010 [54]Weill Cornell Medical College, Department of Urology, New York, NY, USA83 RARC
104 ORC
375
357
460
1,170
41
59
5.5
8
Khan et al., 2012 [55]Multicentric48 RARC
52 ORC
386
320
337
1,351
4
58
42
71
9.9
19.2
Styn et al., 2012 [56]University of Michigan, Ann Arbor, MI, USA50 RARC
100 ORC
455
349
350
475
4
24
66
62
9.5
10.2
Sung et al., 2012 [57]Sungkyunkwan University School of Medicine, Seoul, Korea35 RARC
104 ORC
578
501
448
1063
11
57
1
0
63
74
Kader et al., 2013 [58]Wake Forest University, Winston-Salem, NC, USA100 RARC
100 ORC
451
393
420
983
15
47
35
57
7.8
12.2
Knox et al., 2013 [59]University of Alabama-Birmingham, Birmingham, AL, USA58 RARC
84 ORC
468
396
276
1,522
5
80
24
58
6.3
10.8
Musch et al., 2014 [60]Kliniken Essen-Mitte, Germany100 RARC
42 ORC
410
351
351
810
27
60
3
5
59
93
17.1
19.9
Bochner et al., 2015 [61]Memorial Sloan Kettering Cancer Center, New York, NY, USA60 RARC
58 ORC
456
329
500
681
5.4
4.8
8
8

C = continent; EIC = extracorporeal ileal conduit; IIC = intracorporeal ileal conduit; ORC = open radical cystectomy; RARC = robotic assisted radical cystectomy.

Weighted incidence of severe complications (Clavien 4 and 5) was quoted to be about 2.0% (range: 0–8%). Overall complications were reported for patients that underwent RARC and extracorporeal continent diversion [48] and [49], with a median rate of 78.4% (range: 77–80%). Severe complications classified as Clavien 3b and 4 were reported in 4.5% of patients (range: 4–5%). Two studies reported RARC and intracorporeal conduit diversion [50] and [51] and a weighted overall complication rate of 46.8% (range: 31–63%). Moreover, only one multicentric study reported perioperative outcomes for patients treated with RARC and intracorporeal continent diversion [52]. Desai et al found an overall complication rate of 47%, with a median operative time of 456 min and 460 ml of blood loss during surgery. Only one study assessed severe complications (Clavien 4 and 5) in this population subgroup, reporting a rate of 13%. A comparison of extracorporeal and intracorporeal diversion was conducted by Ahmed et al [53], who found similar rates of overall complications (49% vs 41%) and length of stay (median: 8 vs 9 d) for patients with extracorporeal versus intracorporeal diversion, respectively.

Several reports compared outcomes and complications after ORC and RARC [54], [55], [56], [57], [58], [59], [60], and [61]. Differences were recorded with regard to operative time (median weighted: 436 vs 383 min), blood loss (median weighted: 394 vs 1008 ml), transfusion rate (13.5% vs 52.5%), and overall complications (45.8% vs 65.2%) for patients treated with RARC and ORC, respectively. Length of stay was 9.5 and 11.6 d and intraoperative complication rates were 3.4% and 4.0% for RARC and ORC, respectively.

3.3. Complications and surgical volume

Table 4 summarizes the studies assessing the effect of surgical volume (ie, surgeon or hospital volumes) on the prediction of perioperative outcomes and complications. Better results in terms of perioperative complications after RC were reported in higher volume centers, according to the majority of studies [62], [63], [64], [65], and [66]. A decreased trend of perioperative complications was reported by Kim et al [62], who observed fewer complications in high-volume centers if compared with medium- and low-volume centers. Sun et al [64] assessed, for the first time, the role of the Leapfrog volume thresholds (Leapfrog Group, Washington, DC, USA) for patient safety [67] as a definition of hospital volume. Transfusion rate, median length of stay, and intraoperative and postoperative complications were significantly associated with Leapfrog volume thresholds. These parameters were created by the Leapfrog Group in the evaluation of hospital volume [67] and applied for the first time in RC patients. Barbieri et al [63], using the University Health System Consortium Clinical Database, confirmed these findings only in academic medical centers. Moreover, patients treated at residency and cancer teaching center institutions showed better results in terms of perioperative complications after RC [68] in comparison to patients treated in nonteaching institutions.

Table 4 Impact of surgical volume (hospital and surgeon) on perioperative outcomes in open radical cystectomy and robot assisted radical cystectomy

Barbieri et al., 2007 [63]Kim et al., 2012 [62]Sun et al., 2014 [64]Mayer et al., 2011 [66]Santos et al., 2015 [65]Leow et al., 2015 [69]Hayn et al., 2011 [71]Azzouni et al., 2013 [72]Hayn et al., 2010 [73]
InstitutionMulticentricMulticentricMulticentricMulticentricMulticentricMulticentricRoswell Park
Cancer Institute,
Buffalo, NY, USA
Roswell Park
Cancer Institute,
Buffalo, NY, USA
Multicentric
No. of cases672850 62545 3548596277849 792164100482
Hospital volume definitionRC/year: ≤3, 3–10, 11–25, 26–50, ≥50RC/year: overall, <1.5, 1.5–5.0, >5.0LVT: 0,1,2,3,4,5RC/year: 2–9, 10–15, ≥16Hospital: quartiles 1–4
Surgeon volume definitionRC/year: 6<, 6–8, >8Surgeon: quartiles 1–4Surgeon: quintiles 1–51–50, 51–100, 101–164Overall, 1–25, 26–50, 51–75, 76–100Overall, previous RARP experience: ≥50, 51–100, 101–150, >150
Operative time, min180, 165, 16352, 366, 349, 373, 44385, 421, 338,401, 444
Blood loss, ml566, 631, 521300, 400, 350, 300, 200408, 418, 286, 575, 188
Transfusion, %34.7, 25.9, 30.2, 33.7, 22.6, 19.810, 0, 12, 4, 24
Length of stay, d12.1, 12.0, 11.0, 11.2, 8.99, 9, 8, 9, 8, 99, 7, 9, 10, 9
Intraoperative complications, %3.1, 3.2, 2.7, 1.8, 2.0, 3.1
Postoperative complications, %32.3, 33.1, 28.7, 28.6, 27.1, 34.6Hospital: 28.9, 35.0, 28.8, 30.4
Surgeon: 33.7, 27.5, 28.9, 32.5
68, 62, 40
Overall complications,%37.7, 37.8, 36.0, 36.5, 37.429.3, 31.7, 30.1, 24.7Hospital: 19, 18, 23. Surgeon: 17, 18, 2318.3, 17.1, 14.8, 14.1, 11.4
Readmission, %Hospital: 15, 16, 14. Surgeon: 14, 12, 1421.8, 21.4, 18.7, 18.2, 19.716, 12, 20, 20, 16

LVT = Leapfrog volume thresholds; RARP = robot-assisted radical prostatectomy; RC = radical cystectomy.

Surgeon volume was investigated as a predictor in the evaluation of perioperative outcomes after RC by many reports [65], [66], and [69]. Recently, Santos et al [65] assessed the importance of receiving an RC in a high-volume hospital or by a high-volume surgeon to improve overall survival and to minimize the risk of incurring postoperative complications after surgery. These results were confirmed by Leow et al [69] with the Premier Hospital Database (Premier Inc, Charlotte, NC, USA). They found an inverse relationship between surgeon volume and the development of postoperative major complication rates and readmission after discharge. Moreover, Mayer et al [66] were not able to find any association between hospital or surgeon volumes and complication or readmission rates; however, this study reported only short-term outcomes after RC, and further high-quality data are needed to confirm these findings [70].

With regard to robotic surgery, only two studies assessed the impact of surgical volume on perioperative outcomes [71] and [72]. Hayn et al [71] found longer operative time but no differences in operative and postoperative complications in the first 100 RARCs performed at a single institution compared with the subsequent 64 RARCs performed at the same center. From the same institution, Azzouni et al [72] evaluated the first 100 consecutive patients treated with RARC and robot-assisted intracorporeal ileal conduits (RICICs) at a single institution (Roswell Park Cancer Institute, Buffalo, NY, USA). Patients were stratified in quartiles, and no differences were recorded in terms of readmission at 30 d, readmission at 90 d, or perioperative complications. Nevertheless, considering that only 100 patients from a single institution were included in this study, further evaluation is needed to assess the impact of surgical volume on perioperative complications after RICIC. One study assessed the impact of prior robotic assisted radical prostatectomy (RARP) experience on outcomes at RARC and found better results in terms of operative time and blood loss for surgeons with previous RARP experience [73].

3.4. Perioperative strategies to reduce the risk of complications

As noted, perioperative complications are common in RC patients; therefore, strategies to reduce them should be pursued by urologists. Accurate preoperative patient selection is fundamental to reducing 90-d mortality and high-grade complications [74]. In context, age and preoperative albumin levels should be taken in account by physicians [74] and [75]. In contrast, several frailty indexes have been developed in general surgery and have shown promising results for preoperative patient selection but need further evaluation in the field of RC [76].

Regardless of chronologic age, preoperative nutritional deficiency has been related to poor surgical and oncologic outcomes [77]. Preoperative parameters such as albumin levels can be helpful for evaluating preoperative nutritional status. Supplementation with enteral arginine-based solutions in pre- and postoperative settings seems effective in high-risk elective surgical patients for the reduction of infectious complications and hospital length of stay [78]. In recent prospective trials comparing total parenteral nutrition plus oral nutrition and oral nutrition alone following RC, patients treated with total parenteral nutrition recorded higher cost and higher postoperative complications than patients treated with oral nutrition [79]. Bowel preparation has historically been considered the standard of care for major abdominal surgeries; however, recent data suggest that mechanical bowel preparation does not affect the reported rates of perioperative infectious, wound, or bowel complications. Consequently, if only small bowel is used, no evidence supports benefits with bowel preparation [80].

A moderately restrictive fluid regimen has shown significant reduction of 25% of complications in patients treated with pancreaticoduodenectomy [81]. Restriction of fluid has shown promising results in achieving an earlier return of bowel function and reducing blood transfusion and rates of cardiopulmonary, wound, and anastomotic complications [81]. In RC patients, this strategy has been shown to be effective in reducing postoperative ileus and nausea [82]. Enhanced Recovery After Surgery (ERAS) is a multifaceted approach involving intervention in preoperative, intraoperative, and postoperative settings. It has been developed for colorectal surgery, but its application is rapidly increasing in RC patients. A recent meta-analysis estimated a reduction of 30% in complications within 30 d after surgery in several surgical interventions [83]. The ERAS Society created a group focused on major urologic procedures and released a protocol for RC patients [84]; however, the real benefits of ERAS remain understudied in RC patients and need to be validated prospectively to assess benefits in terms of complications and costs [85]. Finally, a recent multi-institution randomized placebo-controlled trial demonstrated the positive effect of alvimopan in the reduction of postoperative ileus and length of stay [86].

4. Conclusions

RC is a highly complex procedure with a recognized high risk of perioperative complications and adverse outcomes. RARC is feasible, and several reports demonstrated consistent reduction in blood loss during surgery and, consequently, in perioperative transfusion rates; however, the incidence of perioperative complications seems comparable to that of ORC series. Hospital and surgeon volumes appear to be related to a reduction of complications after surgery, suggesting the need to centralize treatment to dedicated surgeons in tertiary referral centers. Further studies are warranted to standardize the definition of complications and to develop appropriate strategies aimed at minimizing complications.


Author contributions: Marco Moschini 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: Moschini, Simone, Stenzl, Gill, Catto.

Acquisition of data: Moschini, Simone.

Analysis and interpretation of data: Moschini, Simone, Catto.

Drafting of the manuscript: Moschini, Simone, Stenzl, Gill, Catto.

Critical revision of the manuscript for important intellectual content: Stenzl, Gill, Catto.

Statistical analysis: Moschini.

Obtaining funding: Moschini, Simone, Stenzl, Gill, Catto.

Administrative, technical, or material support: Moschini, Simone, Stenzl, Gill, Catto.

Supervision: Stenzl, Gill, Catto.

Other (specify): None.

Financial disclosures: Marco Moschini 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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Footnotes

a Unit of Urology/Division of Oncology, IRCCS Ospedale San Raffaele, URI Milan, Milan, Italy

b Department of Urology, “Regina Elena” National Cancer Institute, Rome, Italy

c Department of Urology, University Hospital Tübingen, Tübingen, Germany

d University of Southern California Institute of Urology, Keck School of Medicine, Catherine and Joseph Aresty Department of Urology, Los Angeles, CA, USA

e Academic Urology Unit, University of Sheffield, Sheffield, UK

Corresponding author. Department of Urology, Urological Research Institute, Vita-Salute University, San Raffaele Scientific Institute, Magna Græcia University of Catanzaro, Via Olgettina, 58, Milan, 20132, Italy. Tel. +39 3471857321; Fax: +39 26435664.

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