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Systematic review of perioperative outcomes and complications after open, laparoscopic and robot-assisted radical cystectomy
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Actas Urol Esp. 2017;xxx(xx):xxx---xxx
Actas Urol´ ogicas Espa˜ nolas www.elsevier.es/actasuro
REVIEW ARTICLE
Systematic review of perioperative outcomes and complications after open, laparoscopic and robot-assisted radical cystectomy夽 A. Palazzetti, R. Sanchez-Salas ∗ , P. Capogrosso, E. Barret, N. Cathala, A. Mombet, D. Prapotnich, M. Galiano, F. Rozet, X. Cathelineau Departamento de Urología, L’Institute Mutualiste Montsouris, París, France Received 9 May 2016; accepted 12 May 2016
KEYWORDS Radical cystectomy; Robotic; Laparoscopy; Perioperative outcomes; Complications
PALABRAS CLAVE Cistectomía radical; Robótica; Laparoscopia; Resultados perioperatorios; Complicaciones
Abstract Radical cystectomy and regional lymph node dissection is the standard treatment for localized muscle-invasive and for high-risk non-muscle-invasive bladder cancer, and represents one of the main surgical urologic procedures. The open surgical approach is still widely adopted, even if in the last two decades efforts have been made in order to evaluate if minimally invasive procedures, either laparoscopic or robot-assisted, might show a benefit compared to the standard technique. Open radical cystectomy is associated with a high complication rate, but data from the laparoscopic and robotic surgical series failed to demonstrate a clear reduction in post-operative complication rates compared to the open surgical series. Laparoscopic and robotic radical cystectomy show a reduction in blood loss, in-hospital stay and transfusion rates but a longer operative time, while open radical cystectomy is typically associated with a shorter operative time but with a longer in-hospital admission and possibly a higher rate of high grade complications. © 2017 Published by Elsevier Espa˜ na, S.L.U. on behalf of AEU.
Revisión sistemática de resultados perioperatorios y complicaciones después de cistectomía radical abierta, laparoscópica y asistida por robot Resumen La cistectomía radical y disección de los ganglios linfáticos regionales es el tratamiento estándar para el cáncer vesical músculo invasivo localizado y no músculo-invasivo de alto riesgo, y representa uno de los principales procedimientos quirúrgicos urológicos. El abordaje quirúrgico abierto es todavía ampliamente adoptado, aunque en las últimas 2 décadas se han hecho esfuerzos con el fin de evaluar si los procedimientos mínimamente invasivos, ya
夽 Please cite this article as: Palazzetti A, Sanchez-Salas R, Capogrosso P, Barret E, Cathala N, Mombet A, et al. Revisión sistemática de resultados perioperatorios y complicaciones después de cistectomía radical abierta, laparoscópica y asistida por robot. Actas Urol Esp. 2017. http://dx.doi.org/10.1016/j.acuro.2016.05.009 ∗ Corresponding author. E-mail address: [email protected] (R. Sanchez-Salas).
2173-5786/© 2017 Published by Elsevier Espa˜ na, S.L.U. on behalf of AEU.
ACUROE-932; No. of Pages 10
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A. Palazzetti et al. sean laparoscópicos o asistidos por robot, podrían mostrar un beneficio en comparación con la técnica estándar. La cistectomía radical abierta se asocia con una alta tasa de complicaciones, pero los datos de la serie quirúrgica laparoscópica y robótica no lograron demostrar una clara reducción en las tasas de complicaciones postoperatorias en comparación con la serie quirúrgica abierta. La cistectomía radical laparocópica y robótica muestran una reducción en la pérdida de sangre, las tasas de estancia hospitalaria y de transfusión, pero un mayor tiempo operatorio, mientras que la cistectomía radical abierta se asocia típicamente con un tiempo operatorio más corto, pero con un ingreso más largo en el hospital y, posiblemente, una mayor tasa complicaciones de alto grado. © 2017 Publicado por Elsevier Espa˜ na, S.L.U. en nombre de AEU.
Introduction Radical cystectomy (RC) with regional lymph node dissection (LND) is the standard treatment for localized muscle-invasive and for high-risk non-muscle-invasive bladder cancer.1 Concerning the surgical technique adopted, open radical cystectomy (ORC) is still the most commonly used surgical approach worldwide.2 Nevertheless, in the last fifteen years, minimally invasive techniques such as laparoscopic RC (LRC) and robot-assisted RC (RARC) have gained popularity and have been widely performed in many international centers in order to possibly reduce the high percentage of complications that the procedure still harbors.3,4 To date, hundreds of single institutions surgical series evaluating peri-operative outcomes and complications of minimally invasive approaches are available. Their results are promising, and nowadays mid- and long-term oncologic results are becoming more and more available, allowing for a proper comparison between the three different surgical techniques.5,6 The retrospective nature of most papers published and the lack of randomized controlled trials and high level of evidence literature represent a main drawback. To date, only few RCTs are available.7,8 Among them, the Cystectomy Open Robotic and Laparoscopic (CORAL) trial is the only available comparing LRC to ORC and RARC in a single institution. In this wide and continuously changing scenario, the aim of the present systematic review is to report on complications and peri-operative outcomes of ORC, LRC and RARC in order to clarify the role and the possible pros and cons of minimally invasive surgery applied to RC.
Methods Evidence acquisition A systematic search of the literature was performed in February 2016 using Medline database and according to current methodological recommendation for systematic reviews.9 The search included a free-text protocol using the terms radical cystectomy in all the fields of the records. Limits were applied to only English literature. Two authors (A.P. and R.S.S.) reviewed the results records selecting the studies that compared RARC to LRC or to ORC and
RARC, LRC and ORC case series. Other significant studies cited in the reference list of the selected papers were evaluated. Studies reporting on salvage cystectomy, partial cystectomy, prostate-sparing cystectomy, single-case reports, single-site laparoscopic case series, natural-orifice trans-luminal endoscopic surgery, congress abstracts, book chapters, review papers, editorials, comments, letters to the editors, experimental models, surgical technique-only papers or animal series were not included in the present review. All papers reporting on peri-operative outcomes (operative time, blood loss, in-hospital stay, readmission rate, post-operative complication rate) of RARC, LRC and ORC were included in the qualitative analysis. All papers were categorized according to the 2011 LOEs for treatment benefits: LOE 1, systematic review of randomized trials or n-of-1 trials; LOE 2, randomized trials or observational study with dramatic effect; LOE 3, non-randomized controlled cohort/follow-up study; LOE 4, case-series, casecontrol studies, or historically controlled studies; LOE 5, mechanism-based reasoning.10 Methodological reporting of complications was evaluated according to the Martin criteria.11
Results Quality of the studies and level of evidence The flowchart of the systematic review of the literature performed is shown in Fig. 1. In total, 5771 records were identified in the PubMed database. After excluding duplicate or triplicate publications and non-relevant records, a total of 52 studies have been included in the final qualitative analysis reporting on complications and perioperative outcomes. The majority of the surgical series included are retrospective, single-center studies with the exception of some prospective studies, and multicenter collaboration papers. All of them are categorized as LOE 4. There were only two randomized compared studies available (LOE 2b) representing the highest level of evidence published to date. Table 1 describes the baseline characteristics of the patients included in the surgical series (median age, ASA score classification, pathologic stage distribution) of the three different techniques.
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Open laparoscopic and robot-assisted radical cystectomy
3
Records identified through pubmed database searching (n=5771)
Screening
Records after duplicates or not relevant removed (n=188)
Eligibility
Records screened (n=150)
Included
Full-text articles assessed for eligibility (n=112)
Studies included in qualitative synthesis (n=35)
Figure 1
Full-text articles excluded, because included in multicentric studies or systematic reviews (n=77)
Flowchart of the systematic review performed.
Peri-operative outcomes after ORC, LRC and RARC Open radical cystectomy Table 2 summarizes mean operative time, mean blood loss, transfusion rate, overall 90-days complication rate, Table 1 Baseline patient’s characteristics in the ORC, LRC and RARC surgical series. Open
Laparoscopic
Robotic
Baseline Median age (years)
67
64
67
ASA score % 1 2 3 4
14.4 35.1 50.2 4.7
16.4 49.7 21.6 0.5
6 54.9 38.5 0.5
Pathologic stage % Tis
9.5 8.1 21.6 25.7 22.6 14.9
0.2 1.2 23 33.7 32.8 4.9
7.2 9.5 15.3 35.9 23.4 9.2
ASA, American Society of Anesthesiologists.
Records excluded because not respected the inclusion criteria (n=38)
in-hospital stay, and re-admission rate in the ORC surgical series.12---28 Despite the large number of papers reporting on peri-operative outcomes, only a few of them used standardized criteria allowing for a proper comparison of the abovementioned outcomes. All the surgical series revised retrospectively collected their data. Once duplicate publications and collaborative studies were excluded, mean operative time was 329 min (range: 100---862 min), overall mean blood loss was 918 ml (range: 100---4200 ml), transfusion rate ranged between 31 and 82.4%. Mean in-hospital stay was 13.5 days (range: 6---39 days); readmission rate, when reported, ranged between 18 and 26%. The overall complication rate ranged between 22 and 68%.
Laparoscopic radical cystectomy Table 3 summarizes mean operative time, mean blood loss, transfusion rate, overall 90-days complication rate, in-hospital stay, and re-admission rate in the LRC surgical series. Fifty percent of the series revised collected their data prospectively. Again, once duplicate publications and collaborative studies were excluded, mean operative time was 379 min (range: 260---600 min), overall mean blood loss was 432 ml (range: 270---720 ml), transfusion rate ranged between 0 and 32.5%. Mean in-hospital stay was 11 days (range: 9---14 days); readmission rate was reported in only
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Table 2
Perioperative outcomes reported in open radical cystectomy series. Year
Article type
Type of diversion: 1. Ileal conduit 2. Neobladder 3. Other 4. Not reported
No. cases
Mean operative time (min)
Mean blood loss (ml)
Transfusion rate (%)
Mean in-hospital stay (days)
Readmission rate (%)
Overall complication rate (%)
Study period
Takada N. Shabsigh A. Novara G. Ramani V. Lavallée L. Novotny V. Isbarn H. Stimons C.J. Schiavina R. De Nunzio C. Chang S.S. Studer U. Lowrance W.T. Konety B.R. Rosario D.J. Madersbacher S. Hautmann R.E.
2012 2009 2009 2009 2014 2007 2009 2010 2013 2013 2002 2006 2008 2006 2000 2003 2010
Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective
1,2 1,2 1,2 4 1,2 1,2 4 4 1,2 1,2 1,2 2 1,2 1,2 1,2 1 2
928 1142 358 846 2303 516 8263 753 404 467 304 482 557 6577 101 382 1540
393 360 300 ----360 ----370 270 292 --287 ---------
1300 1000 600 ----1208 ----750 1290 600 --600 ---------
--66% 67% --38% 82.4% ----40.8% 39% 31.5% --38% ---------
39 9 17 --8 19 --6 15 13 7 --6.8 9 -------
--26% ----------26.6% --------18% ---------
68% 64% 49% --55% 27.3% ----39.9% 65% 36.1% 33% 41% 28.4% 22% 66% 57.9%
------1970---2005 2006---2012 1993---2005 --2001---2007 1995---2009 2011---2012 1995---2000 1985---2005 2000---2005 --1992---1997 1971---1995 1986---2008
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Year
Article type
Type of diversion: 1. Ileal conduit 2. Neobladder 3. Other 4. Not reported
Cases Mean operative time (min)
Blood loss (ml)
Transfusion rate (%)
In-hospital stay (days)
Readmission Overall rate (%) complication rate (%)
Follow-up (days) --or study period when follow-up not available
Moinzareh A.
2005
Prospective
Cathelineau X. Castillo O.A. Hemal A.K. Haber G.P. Park B. Albissini S. Huang J. Fontana P.P. Springer C. Gillion N. Aboumarzouk O.M.
2005 2006 2008 2007 2013 2015 2010 2015 2014 2010 2012
Retrospective Retrospective Retrospective Retrospective Retrospective Prospective Prospective Retrospective Prospective Prospective Prospective
1 2 1,2 1,2,3 1,2 1,2 1 1,2 2 1,2 2 1,2 1,2
8 3 84 59 48 37 30 503 171 102 37 40 65
300 600 550 488 456 378 275 500 270 432 410 720 249
12.5 0 5 20 44 3 13.3 --17 14.5 5.4 32.5 ---
----12 --10.2 --12 14 13.1 13 12 10.2 9
0 33.3 -----------------------
244 218 --------16 (0.8---42.6) 50 (19---90) 1110 (90---2490) 2005---2012 2009---2011 2004---2008 2006---2011
480 600 260 337 310 380 528 325 325 355 330 407 294
36% 8% 42% --11% 43.3% ----51.5% --32.5% 44.6%
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Perioperative outcomes reported in laparoscopic radical cystectomy series.
Open laparoscopic and robot-assisted radical cystectomy
Table 3
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62 55 59 50 31 50.5 ----38 ------8 11.9 8.6 16.73 --17.1 ----19.4 --19 --516 585 378.7 385 --345.3
Transfusion rate (%) Blood loss (ml) Cases Median, mean operative time (min) Type of diversion: 1. Ileal conduit 2. Neobladder 3. Other 4. Not reported
2015 2015 2015 2015 2015 2015 Bochner B.H. Khan M.S. Novara G. Swentner C. Koupparis A. Sim A.
Article type Year Reference
Radical cystectomy and lymph node dissection for the treatment of bladder neoplasm is one of the main urologic surgical procedures and is associated with a reported rate of peri-operative complications as high as 68% in large surgical series.12 This rate is now reducing over time because of more sophisticated postoperative care as well as improved anaesthesiologic and surgical techniques, but it still remains higher than 30% in the early postoperative period.45,46 Since its overwhelming success with renal and prostatic surgery, minimally invasive approaches, either robot-assisted or laparoscopic, have been more and more used with the aim of reducing complication rates and enhancing peri-operative outcomes, maintaining non-inferior oncologic results as the gold standard ORC. Robot-assisted radical cystectomy is nowadays performed in the United States in 20% of all cases.2 In the last two decades, many surgical series and comparative studies have been published, which compared minimally invasive techniques to ORC. The present review
Perioperative outcomes reported in robot-assisted radical cystectomy series.
Discussion
Table 4
Table 5 reports the summary of the 90-day complication rates according to modified Clavien classification whenever possible and the 90-day mortality rates after ORC, LRC, and RARC. Only few papers reported strictly grade one-tofive complication rates for their patients. In the majority of the studies, the author divided low-grade (Clavien 1---2) and high-grade (Clavien 3---5) complications. In the ORC series, low-grade complication rates ranged between 34 and 51%, while high-grade complications ranged between 5.2 and 21.8%. Ninety-days mortality rate ranged between 0.3 and 6.9%. In the LRC series assessing the percentage of complications, it was not possible because the majority of authors described the single events without giving data on their relative percentage. What is underlined from the data collected is the relatively low proportion of highgrade events. Ninety-days mortality rate ranged between 0 and 16.6%. Concerning the RARC surgical series, Clavien 1---2 complications ranged between 23 and 44% while highgrade between 9 and 36%. Ninety-days mortality rate ranged between 0 and 2.4%.
In-hospital stay (days)
Complications and mortality after ORC, LRC and RARC
456 389 385 476.9 --402.3
Readmission Overall rate (%) complication rate (%)
Robot-assisted radical cystectomy Table 4 summarizes mean operative time, mean blood loss, transfusion rate, overall 90-days complication rate, inhospital stay, and re-admission rate in the RARC surgical series. The results of two randomized controlled trials and of a large systematic review and cumulative analysis are available for RARC outcomes and therefore reported. Mean operative time was 421.8 min (range: 385---476 min), overall mean blood loss was 442 ml (range: 345---585 ml), and the transfusion rate reported is 19%. Mean in-hospital stay was 12.4 days (range: 8---17 days); readmission rate was reported in only one study and was 38%. Overall complication rate ranged between 30 and 62%.5,7,41---44
60 20 5456 62 102 101
Follow-up (days) --or study period when follow-up not available
one study and was 33.3%. The overall complication rate ranged between 11 and 51.5%.29---40
--365 --1119 --2009---2014
A. Palazzetti et al.
1,2 1,2 1,2 2 1,2 2
6
RCT RCT Syst. review Retrospective Prospective Retrospective
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7
Complications according to Clavien classification and 90-days mortality rates following ORC, LRC and RARC.
Reference
Year
90-days complication rate Clavien (%) Grade 1
Open RC series: Takada N. Shabsigh A. Novara G. Ramani V. Lavallée L. Novotny V. Isbarn H. Stimons C.J. Schiavina R. De Nunzio C. Chang S. S. Studer U. Lowrance W.T. Konety B.R. Rosario D.J. Madersbacher S. Hautmann R.E.
2012 2009 2009 2009 2014 2007 2009 2010 2013 2013 2002 2006 2008 2006 2000 2003 2010
23% 11% 6% ----------14.3% ---
Laparoscopic RC series: Moinzareh A.
2005
-----
Cathelineau X. Castillo P. Hemal A.K. Haber G.P. Park B. Albissini S. Huang J. Fontana P.P. Springer C. Gillion N. Aboumarzouk O.M.
2005 2006 2008 2007 2013 2015 2010 2015 2014 2010 2012
Robot-assisted RC series: Bochner B.H. 2015 Khan M.S. 2015 Novara G. 2015 Swentner C. 2015 Koupparis A. 2015 Sim A. 2015
---------
Grade 2 28% 40% 28% ----------20% --30.9% --38% ------36.1%
----14 events ----16.6% ----0 5 events 71 events 140 events 11 events 33 events 37.7% 49.1% 0 21.6% ----33.8% 6.1%
9% 11.9%
--25% 44.5% 24.2% 14% 15.8%
summarizes the results of these studies regarding perioperative outcomes and complications rates. Concerning perioperative outcomes, the data reported show how either LRC or RARC can offer a reduced expected blood loss and transfusion rates compared to ORC. Among minimally invasive approaches, RARC is associated with a higher blood loss compared to LRC but with an inferior transfusion rate. These data are in accordance with previous results from a large systematic review and meta-analysis of perioperative outcomes of RARC conducted by Novara et al., based on the revision of 70 surgical robotic case series and 23 comparative studies.5 When considering operative time, both RARC and LRC have longer operative times compared to ORC and between minimally invasive approaches RARC has the
90-days mortality rate
Grade 3
Grade 4
Grade 5
15% 12% 8% ----------9.1% ---
0.8% 0.2% 3% ----------1.2% ---
2% 2.7% 3% ----------4.4% --0.3% 1.7% 1.7% -------
4.9% ---
--7.4%
-------
------21.8%
-----
----1 event ----10.4% ----4 events 0 89 events 6 events 20 events --13.2% 0 0 0 ----0 0
6% 27.7%
13% 30% 15% 25.8% 1% 8.9%
------------0 10 events --1.9% 0 --4.6%
2% 2.7% 3% 0.4---13.5% 2.9% 0.8% 3.9% 6.9% 4.4% 1.7% 0.3% 1.7% 1.7% 2.57% 1.98% --2.3% 0 33.3% --3.3% 2% --0 2% 16.6% 1.9% ----4.6% --0 2.4%
2% 0
0.9% 0
longest. Even in high-volume centers with the most experienced surgeons in laparoscopy and robotic surgery, operative time remains higher than ORC. Overall mean in-hospital stay was 13.5 days in ORC, 11 in LRC, and 12.4 in RARC thus reflecting a somehow comparable time-lapse among the three approaches. This parameter, however, is full of possible misinterpretations as long as it is influenced by single hospital regulations. Some institutions, in fact, as a standard policy, admit patients one or two days before surgery, thus, modifying the interpretation of the in-hospital stay data. The re-admission rate was relatively under-reported in the analyzed papers, but its values were almost always >20%, thus reflecting a very high rate of second hospitalizations due to RC complications even in high-volume centers.
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8 Concerning post-operative complications, since 2002, recommendations exist on how to properly report on them. An ideal methodology for reporting adverse events related to surgical therapy should include 10 established basic reporting criteria11 : (1) a clear description of the method of data acquisition, (2) an indication of the duration of follow-up, (3) an indication of whether or not outpatient complication data are included, (4) definitions/inclusion criteria of at least one complication, (5) an indication of the mortality rate and cause of death, (6) an indication of the morbidity rate (number of patients and the total number of complications recorded), (7) an indication of procedurespecific complications, (8) the utilization of a grading system to clarify severity of complications, (9) an indication of the median or mean length of stay, and (10) an indication of the methodology utilized to assess patient risk stratification (e.g., Charlson-Romano index, ASA scoring). Despite that, many inhomogeneous reporting methods are still used in the literature, with a huge lack in information, which make comparison between the outcomes of different institutions, surgeons or surgical techniques almost impossible. Furthermore, as long as post-operative complications are also used as a surrogate of quality of surgery and care, other than surgical competency, the importance of standardizing the reporting method must be stressed and underlined. Shabsigh et al.12 in a large retrospective study defining early morbidity of RC found a 64% complication rate, which is much higher compared to other similar series.25 This difference is most probably due to differences in reporting data and in defining the type of complications rather than to a difference in surgical experience or technique. Few studies evaluated independent predictors of postoperative complications including multivariable analysis, and those are mainly in the ORC series. Chang et al.22 found ASA score, transfusion need, and intensive-care unit admission as predictive factors for high-grade complications. The same results regarding ASA score classification were also found in a large retrospective analysis from the Memorial Sloan Kettering Cancer Centre where Shabsigh et al.12 found as general predictors of post-operative mortality gender, ASA score, and the type of urinary diversion. Other predictive factors of mortality described are pathologic stage, histologic subtype, low pre-operative albumin level, operative time >6 h, and previous abdominal surgery.29---40 In the LRC series, there are no studies specifically analyzing independent predictors of perioperative outcomes and complications but both Castillo et al.31 and Haber et al.33 found a progressive reduction in complications and operative time with progressive case-load increase. On the other hand, Aboumarzouk et al.40 found no link with increased case-load and perioperative outcomes. In the RARC series, more interesting data come from three RCTs.7,41,42 In the first one, Bochner et al. randomized 58 patients to ORC vs 60 to RARC. The results of this randomized trial showed complication rates of 90 days after surgery, of 62% and 66% in the RARC and ORC arms, respectively, using an ITT analysis. At the mandated interim analysis of this protocol, the similarity in complication rates met the trial’s predetermined futility criteria and led to the early closure of the trial. This trial thus failed to demonstrate any significant beneficial effect on complications of RARC vs ORC. The second RCT is the CORAL trial where Khan et al.
A. Palazzetti et al. randomized patients into three arms: ORC, LRC, and RARC for the first time in the literature. The results of the CORAL trial are biased by the poor number of patients randomized, but nevertheless they fail to find a benefit in complication rate between ORC and RARC while, on the other hand, finding a significant advantage in the LRC arm. The third one, by Parekh et al.,42 randomizing 20 patients in the open arm and 20 in the robotic one also confirmed the same concepts. The results of a multicentric large phase three randomized controlled trial, the RAndomiZed Open vs Robotic cystectomy trial (RAZOR)8 are not awaited before 2016---2017. Finally, we can consider that major complications occur in the reconstructive part of radical cystectomy, which is performed extracorporally in the majority of the studies included. This data might explain why minimally invasive techniques show a benefit in terms of blood loss, which is prevalent in the demolition part of surgery, but not in terms of post-operative complications, which are mainly related to the diversion itself. Only a few institutions are now performing totally intracorporeal urinary diversion, and more comparative studies are needed to better conclude on this topic.
Conclusions Despite the efforts to reduce morbidity of RC, complication rates of minimally invasive approaches remain high. A trend toward high-grade complication rates of less than 90 days is seen with LRC and RARC. Laparoscopic radical cystectomy and RARC, moreover, offer less blood loss and transfusion rates compared to ORC. Operative time, however, remains longer even in high-volume centers compared to the standard open approach. Further studies are needed to clarify if minimally invasive surgery, either LRC or RARC, might show a real benefit over ORC and not just non-inferiority results.
Conflict of interest The authors declare that they have no conflict of interest.
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9 23. Studer UE, Burkhard FC, Schumacher M, Kessler TM, Thoeny H, Fleischmann A, et al. Twenty years experience with an orthotopic low pressure bladder substitute-lessons to be learned. J Urol. 2006;176:161---6. 24. Lowrance WT, Rumohr JA, Chang SS, Clark PE, Smith JA Jr, Cookson MS. Contemporary open radical cystectomy: analysis of perioperative outcomes. J Urol. 2008;179:1313---8. 25. Konety B, Allareddy V, Herr H. Complications after radical cystectomy: analysis of population-based data. Urology. 2006;68:58---64. 26. Rosario DJ, Becker M, Anderson JB. The changing pattern of mortality and morbidity from radical cystectomy. BJU Int. 2000;85:427---30. 27. Madersbacher S, Schmidt J, Eberle JM, Thoeny HC, Burkhard F, Hochreiter W, et al. Long-term outcome of ileal conduit diversion. J Urol. 2003;169:985---90. 28. Hautmann R, Petriconi R, Volkmer B. Lessons learned from 1,000 neobladders: the 90-days complication rate. J Urol. 2010;184:990. 29. Moinzadeh A, Gill IS, Desai M, Finelli A, Falcone T, Kaouk J. Laparoscopic radical cystectomy in the female. J Urol. 2005;173:1912---7. 30. Cathelineau X, Arroyo C, Rozet F, Barret E, Vallancien G. Laparoscopic assisted radical cystectomy: the montsouris experience after 84 cases. Eur Urol. 2005;47:780---4. 31. Castillo OA, Abreu SC, Mariano MB, Tefilli MV, Hoyos J, Pinto I, et al. Complications in laparoscopic radical cystectomy. the South American experience with 59 cases. Int Braz J Urol. 2006;32:300---5. 32. Hemal AK, Kolla SB, Wadhwa P, Dogra PN, Gupta NP. Laparoscopic radical cystectomy and extracorporeal urinary diversion: a single centre experience of 48 cases with three years of follow-up. Urology. 2008;71:41---6. 33. Haber GP, Campbell SC, Colombo JR, Fergany AF, Aron M, Kaouk J, et al. Perioperative outcomes of laparoscopic radical cystectomy: ‘‘pure laparoscopic’’ and ‘‘open assisted’’ approaches. Urology. 2007;70:910---5. 34. Park B, Jeong BC, Jeon SS, Lee HM, Choi HY, Seo SI, et al. Pure laparoscopic radical cystectomy with ileal conduit: a single surgeon’s mid-term outcomes. Yonsei Med J. 2013;54:912---20. 35. Albissini S, Rassweiler J, Abbou CC, Cathelineau X, Chlosta P, Fossion L, et al. Long-term analysis of oncological outcomes after laparoscopic radical cystectomy in Europe: results from a multicentre study by the European Association of Urology (EAU) section of uro-technology. BJU Int. 2015;115:937---45. 36. Huang J, Lin T, Liu H, Xu K, Zhang C, Jiang C, et al. Laparoscopic radical cystectomy with orthotopic ileal neobladder for bladder cancer: oncologic results of 171 cases with a median three years follow-up. Eur Urol. 2010;58:442---9. 37. Fontana PP, Gregorio SA, Rivas JG, Sánchez LC, Ledo JC, Gómez ÁT, et al. Perioperative and survival outcomes of laparoscopic radical cystectomy for bladder cancer in patients over 70 years. Cent European J Urol. 2015;68:24---9. 38. Springer C, Mohammed N, Alba S, Theil G, Altieri VM, Fornara P, et al. Laparoscopic radical cystectomy with extracorporeal ileal neobladder for muscle-invasive urothelial carcinoma of the bladder: technique and short-term outcomes. World J Urol. 2014;32:407---12. 39. Gillion N, Xylinas E, Durand X, Ploussard G, Vordos D, Allory Y, et al. Mid-term oncological control after laparoscopic radical cystectomy in men: a single-centre experience. BJU Int. 2011;108:1180---4. 40. Aboumarzouk OM, Drewa T, Olejniczak P, Chlosta PL. Laparoscopic radical cystectomy: a 5 year review of a single institute’s operative data and complications and a systematic review of the literature. Int Braz J Urol. 2012;38:330---40. 41. Bochner BH, Dalbagni G, Sjoberg DD, Silberstein J, Keren Paz GE, Donat SM, et al. Comparing open radical cystectomy and
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10 robot-assisted laparoscopic radical cystectomy: a randomized clinical trial. Eur Urol. 2015;67:1042---50. 42. Parekh DJ, Messer J, Fitzgerald J, Ercole B, Svatek R. Perioperative outcomes and oncologic efficacy from a pilot prospective randomized clinical trial of open versus robot assisted radical cystectomy. J Urol. 2013;189:474---9. 43. Schwentner C, Sim A, Balbay MD, Todenhöfer T, Aufderklamm S, Halalsheh O, et al. Robot-assisted radical cystectomy and intracorporeal neobladder formation: on the way to a standardized procedure. World J Surg Oncol. 2015;13:3---6. 44. Koupparis A, Villeda-Sandoval C, Weale N, El-Mahdy M, Gillatt D, Rowe E. Robot-assisted radical cystectomy with intracorporeal
A. Palazzetti et al. urinary diversion: impact on an established enhanced recovery protocol. BJU Int. 2015;116:924---31. 45. Sim A, Balbay D, Todenhöfer T, Aufderklamm S, Halalsheh O, Mischinger J, et al. Robot-assisted radical cystectomy and intracorporeal urinary diversion --- safe and reproducible? Cent European J Urol. 2015;68:18---23. 46. Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol. 2001;19:666---75.
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Actas Urol Esp. 2017;xxx(xx):xxx---xxx
Actas Urol´ ogicas Espa˜ nolas www.elsevier.es/actasuro
REVIEW ARTICLE
Systematic review of perioperative outcomes and complications after open, laparoscopic and robot-assisted radical cystectomy夽 A. Palazzetti, R. Sanchez-Salas ∗ , P. Capogrosso, E. Barret, N. Cathala, A. Mombet, D. Prapotnich, M. Galiano, F. Rozet, X. Cathelineau Departamento de Urología, L’Institute Mutualiste Montsouris, París, France Received 9 May 2016; accepted 12 May 2016
KEYWORDS Radical cystectomy; Robotic; Laparoscopy; Perioperative outcomes; Complications
PALABRAS CLAVE Cistectomía radical; Robótica; Laparoscopia; Resultados perioperatorios; Complicaciones
Abstract Radical cystectomy and regional lymph node dissection is the standard treatment for localized muscle-invasive and for high-risk non-muscle-invasive bladder cancer, and represents one of the main surgical urologic procedures. The open surgical approach is still widely adopted, even if in the last two decades efforts have been made in order to evaluate if minimally invasive procedures, either laparoscopic or robot-assisted, might show a benefit compared to the standard technique. Open radical cystectomy is associated with a high complication rate, but data from the laparoscopic and robotic surgical series failed to demonstrate a clear reduction in post-operative complication rates compared to the open surgical series. Laparoscopic and robotic radical cystectomy show a reduction in blood loss, in-hospital stay and transfusion rates but a longer operative time, while open radical cystectomy is typically associated with a shorter operative time but with a longer in-hospital admission and possibly a higher rate of high grade complications. © 2017 Published by Elsevier Espa˜ na, S.L.U. on behalf of AEU.
Revisión sistemática de resultados perioperatorios y complicaciones después de cistectomía radical abierta, laparoscópica y asistida por robot Resumen La cistectomía radical y disección de los ganglios linfáticos regionales es el tratamiento estándar para el cáncer vesical músculo invasivo localizado y no músculo-invasivo de alto riesgo, y representa uno de los principales procedimientos quirúrgicos urológicos. El abordaje quirúrgico abierto es todavía ampliamente adoptado, aunque en las últimas 2 décadas se han hecho esfuerzos con el fin de evaluar si los procedimientos mínimamente invasivos, ya
夽 Please cite this article as: Palazzetti A, Sanchez-Salas R, Capogrosso P, Barret E, Cathala N, Mombet A, et al. Revisión sistemática de resultados perioperatorios y complicaciones después de cistectomía radical abierta, laparoscópica y asistida por robot. Actas Urol Esp. 2017. http://dx.doi.org/10.1016/j.acuro.2016.05.009 ∗ Corresponding author. E-mail address: [email protected] (R. Sanchez-Salas).
2173-5786/© 2017 Published by Elsevier Espa˜ na, S.L.U. on behalf of AEU.
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A. Palazzetti et al. sean laparoscópicos o asistidos por robot, podrían mostrar un beneficio en comparación con la técnica estándar. La cistectomía radical abierta se asocia con una alta tasa de complicaciones, pero los datos de la serie quirúrgica laparoscópica y robótica no lograron demostrar una clara reducción en las tasas de complicaciones postoperatorias en comparación con la serie quirúrgica abierta. La cistectomía radical laparocópica y robótica muestran una reducción en la pérdida de sangre, las tasas de estancia hospitalaria y de transfusión, pero un mayor tiempo operatorio, mientras que la cistectomía radical abierta se asocia típicamente con un tiempo operatorio más corto, pero con un ingreso más largo en el hospital y, posiblemente, una mayor tasa complicaciones de alto grado. © 2017 Publicado por Elsevier Espa˜ na, S.L.U. en nombre de AEU.
Introduction Radical cystectomy (RC) with regional lymph node dissection (LND) is the standard treatment for localized muscle-invasive and for high-risk non-muscle-invasive bladder cancer.1 Concerning the surgical technique adopted, open radical cystectomy (ORC) is still the most commonly used surgical approach worldwide.2 Nevertheless, in the last fifteen years, minimally invasive techniques such as laparoscopic RC (LRC) and robot-assisted RC (RARC) have gained popularity and have been widely performed in many international centers in order to possibly reduce the high percentage of complications that the procedure still harbors.3,4 To date, hundreds of single institutions surgical series evaluating peri-operative outcomes and complications of minimally invasive approaches are available. Their results are promising, and nowadays mid- and long-term oncologic results are becoming more and more available, allowing for a proper comparison between the three different surgical techniques.5,6 The retrospective nature of most papers published and the lack of randomized controlled trials and high level of evidence literature represent a main drawback. To date, only few RCTs are available.7,8 Among them, the Cystectomy Open Robotic and Laparoscopic (CORAL) trial is the only available comparing LRC to ORC and RARC in a single institution. In this wide and continuously changing scenario, the aim of the present systematic review is to report on complications and peri-operative outcomes of ORC, LRC and RARC in order to clarify the role and the possible pros and cons of minimally invasive surgery applied to RC.
Methods Evidence acquisition A systematic search of the literature was performed in February 2016 using Medline database and according to current methodological recommendation for systematic reviews.9 The search included a free-text protocol using the terms radical cystectomy in all the fields of the records. Limits were applied to only English literature. Two authors (A.P. and R.S.S.) reviewed the results records selecting the studies that compared RARC to LRC or to ORC and
RARC, LRC and ORC case series. Other significant studies cited in the reference list of the selected papers were evaluated. Studies reporting on salvage cystectomy, partial cystectomy, prostate-sparing cystectomy, single-case reports, single-site laparoscopic case series, natural-orifice trans-luminal endoscopic surgery, congress abstracts, book chapters, review papers, editorials, comments, letters to the editors, experimental models, surgical technique-only papers or animal series were not included in the present review. All papers reporting on peri-operative outcomes (operative time, blood loss, in-hospital stay, readmission rate, post-operative complication rate) of RARC, LRC and ORC were included in the qualitative analysis. All papers were categorized according to the 2011 LOEs for treatment benefits: LOE 1, systematic review of randomized trials or n-of-1 trials; LOE 2, randomized trials or observational study with dramatic effect; LOE 3, non-randomized controlled cohort/follow-up study; LOE 4, case-series, casecontrol studies, or historically controlled studies; LOE 5, mechanism-based reasoning.10 Methodological reporting of complications was evaluated according to the Martin criteria.11
Results Quality of the studies and level of evidence The flowchart of the systematic review of the literature performed is shown in Fig. 1. In total, 5771 records were identified in the PubMed database. After excluding duplicate or triplicate publications and non-relevant records, a total of 52 studies have been included in the final qualitative analysis reporting on complications and perioperative outcomes. The majority of the surgical series included are retrospective, single-center studies with the exception of some prospective studies, and multicenter collaboration papers. All of them are categorized as LOE 4. There were only two randomized compared studies available (LOE 2b) representing the highest level of evidence published to date. Table 1 describes the baseline characteristics of the patients included in the surgical series (median age, ASA score classification, pathologic stage distribution) of the three different techniques.
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Open laparoscopic and robot-assisted radical cystectomy
3
Records identified through pubmed database searching (n=5771)
Screening
Records after duplicates or not relevant removed (n=188)
Eligibility
Records screened (n=150)
Included
Full-text articles assessed for eligibility (n=112)
Studies included in qualitative synthesis (n=35)
Figure 1
Full-text articles excluded, because included in multicentric studies or systematic reviews (n=77)
Flowchart of the systematic review performed.
Peri-operative outcomes after ORC, LRC and RARC Open radical cystectomy Table 2 summarizes mean operative time, mean blood loss, transfusion rate, overall 90-days complication rate, Table 1 Baseline patient’s characteristics in the ORC, LRC and RARC surgical series. Open
Laparoscopic
Robotic
Baseline Median age (years)
67
64
67
ASA score % 1 2 3 4
14.4 35.1 50.2 4.7
16.4 49.7 21.6 0.5
6 54.9 38.5 0.5
Pathologic stage % Tis
9.5 8.1 21.6 25.7 22.6 14.9
0.2 1.2 23 33.7 32.8 4.9
7.2 9.5 15.3 35.9 23.4 9.2
ASA, American Society of Anesthesiologists.
Records excluded because not respected the inclusion criteria (n=38)
in-hospital stay, and re-admission rate in the ORC surgical series.12---28 Despite the large number of papers reporting on peri-operative outcomes, only a few of them used standardized criteria allowing for a proper comparison of the abovementioned outcomes. All the surgical series revised retrospectively collected their data. Once duplicate publications and collaborative studies were excluded, mean operative time was 329 min (range: 100---862 min), overall mean blood loss was 918 ml (range: 100---4200 ml), transfusion rate ranged between 31 and 82.4%. Mean in-hospital stay was 13.5 days (range: 6---39 days); readmission rate, when reported, ranged between 18 and 26%. The overall complication rate ranged between 22 and 68%.
Laparoscopic radical cystectomy Table 3 summarizes mean operative time, mean blood loss, transfusion rate, overall 90-days complication rate, in-hospital stay, and re-admission rate in the LRC surgical series. Fifty percent of the series revised collected their data prospectively. Again, once duplicate publications and collaborative studies were excluded, mean operative time was 379 min (range: 260---600 min), overall mean blood loss was 432 ml (range: 270---720 ml), transfusion rate ranged between 0 and 32.5%. Mean in-hospital stay was 11 days (range: 9---14 days); readmission rate was reported in only
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Table 2
Perioperative outcomes reported in open radical cystectomy series. Year
Article type
Type of diversion: 1. Ileal conduit 2. Neobladder 3. Other 4. Not reported
No. cases
Mean operative time (min)
Mean blood loss (ml)
Transfusion rate (%)
Mean in-hospital stay (days)
Readmission rate (%)
Overall complication rate (%)
Study period
Takada N. Shabsigh A. Novara G. Ramani V. Lavallée L. Novotny V. Isbarn H. Stimons C.J. Schiavina R. De Nunzio C. Chang S.S. Studer U. Lowrance W.T. Konety B.R. Rosario D.J. Madersbacher S. Hautmann R.E.
2012 2009 2009 2009 2014 2007 2009 2010 2013 2013 2002 2006 2008 2006 2000 2003 2010
Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective Retrospective
1,2 1,2 1,2 4 1,2 1,2 4 4 1,2 1,2 1,2 2 1,2 1,2 1,2 1 2
928 1142 358 846 2303 516 8263 753 404 467 304 482 557 6577 101 382 1540
393 360 300 ----360 ----370 270 292 --287 ---------
1300 1000 600 ----1208 ----750 1290 600 --600 ---------
--66% 67% --38% 82.4% ----40.8% 39% 31.5% --38% ---------
39 9 17 --8 19 --6 15 13 7 --6.8 9 -------
--26% ----------26.6% --------18% ---------
68% 64% 49% --55% 27.3% ----39.9% 65% 36.1% 33% 41% 28.4% 22% 66% 57.9%
------1970---2005 2006---2012 1993---2005 --2001---2007 1995---2009 2011---2012 1995---2000 1985---2005 2000---2005 --1992---1997 1971---1995 1986---2008
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A. Palazzetti et al.
Year
Article type
Type of diversion: 1. Ileal conduit 2. Neobladder 3. Other 4. Not reported
Cases Mean operative time (min)
Blood loss (ml)
Transfusion rate (%)
In-hospital stay (days)
Readmission Overall rate (%) complication rate (%)
Follow-up (days) --or study period when follow-up not available
Moinzareh A.
2005
Prospective
Cathelineau X. Castillo O.A. Hemal A.K. Haber G.P. Park B. Albissini S. Huang J. Fontana P.P. Springer C. Gillion N. Aboumarzouk O.M.
2005 2006 2008 2007 2013 2015 2010 2015 2014 2010 2012
Retrospective Retrospective Retrospective Retrospective Retrospective Prospective Prospective Retrospective Prospective Prospective Prospective
1 2 1,2 1,2,3 1,2 1,2 1 1,2 2 1,2 2 1,2 1,2
8 3 84 59 48 37 30 503 171 102 37 40 65
300 600 550 488 456 378 275 500 270 432 410 720 249
12.5 0 5 20 44 3 13.3 --17 14.5 5.4 32.5 ---
----12 --10.2 --12 14 13.1 13 12 10.2 9
0 33.3 -----------------------
244 218 --------16 (0.8---42.6) 50 (19---90) 1110 (90---2490) 2005---2012 2009---2011 2004---2008 2006---2011
480 600 260 337 310 380 528 325 325 355 330 407 294
36% 8% 42% --11% 43.3% ----51.5% --32.5% 44.6%
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Perioperative outcomes reported in laparoscopic radical cystectomy series.
Open laparoscopic and robot-assisted radical cystectomy
Table 3
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62 55 59 50 31 50.5 ----38 ------8 11.9 8.6 16.73 --17.1 ----19.4 --19 --516 585 378.7 385 --345.3
Transfusion rate (%) Blood loss (ml) Cases Median, mean operative time (min) Type of diversion: 1. Ileal conduit 2. Neobladder 3. Other 4. Not reported
2015 2015 2015 2015 2015 2015 Bochner B.H. Khan M.S. Novara G. Swentner C. Koupparis A. Sim A.
Article type Year Reference
Radical cystectomy and lymph node dissection for the treatment of bladder neoplasm is one of the main urologic surgical procedures and is associated with a reported rate of peri-operative complications as high as 68% in large surgical series.12 This rate is now reducing over time because of more sophisticated postoperative care as well as improved anaesthesiologic and surgical techniques, but it still remains higher than 30% in the early postoperative period.45,46 Since its overwhelming success with renal and prostatic surgery, minimally invasive approaches, either robot-assisted or laparoscopic, have been more and more used with the aim of reducing complication rates and enhancing peri-operative outcomes, maintaining non-inferior oncologic results as the gold standard ORC. Robot-assisted radical cystectomy is nowadays performed in the United States in 20% of all cases.2 In the last two decades, many surgical series and comparative studies have been published, which compared minimally invasive techniques to ORC. The present review
Perioperative outcomes reported in robot-assisted radical cystectomy series.
Discussion
Table 4
Table 5 reports the summary of the 90-day complication rates according to modified Clavien classification whenever possible and the 90-day mortality rates after ORC, LRC, and RARC. Only few papers reported strictly grade one-tofive complication rates for their patients. In the majority of the studies, the author divided low-grade (Clavien 1---2) and high-grade (Clavien 3---5) complications. In the ORC series, low-grade complication rates ranged between 34 and 51%, while high-grade complications ranged between 5.2 and 21.8%. Ninety-days mortality rate ranged between 0.3 and 6.9%. In the LRC series assessing the percentage of complications, it was not possible because the majority of authors described the single events without giving data on their relative percentage. What is underlined from the data collected is the relatively low proportion of highgrade events. Ninety-days mortality rate ranged between 0 and 16.6%. Concerning the RARC surgical series, Clavien 1---2 complications ranged between 23 and 44% while highgrade between 9 and 36%. Ninety-days mortality rate ranged between 0 and 2.4%.
In-hospital stay (days)
Complications and mortality after ORC, LRC and RARC
456 389 385 476.9 --402.3
Readmission Overall rate (%) complication rate (%)
Robot-assisted radical cystectomy Table 4 summarizes mean operative time, mean blood loss, transfusion rate, overall 90-days complication rate, inhospital stay, and re-admission rate in the RARC surgical series. The results of two randomized controlled trials and of a large systematic review and cumulative analysis are available for RARC outcomes and therefore reported. Mean operative time was 421.8 min (range: 385---476 min), overall mean blood loss was 442 ml (range: 345---585 ml), and the transfusion rate reported is 19%. Mean in-hospital stay was 12.4 days (range: 8---17 days); readmission rate was reported in only one study and was 38%. Overall complication rate ranged between 30 and 62%.5,7,41---44
60 20 5456 62 102 101
Follow-up (days) --or study period when follow-up not available
one study and was 33.3%. The overall complication rate ranged between 11 and 51.5%.29---40
--365 --1119 --2009---2014
A. Palazzetti et al.
1,2 1,2 1,2 2 1,2 2
6
RCT RCT Syst. review Retrospective Prospective Retrospective
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7
Complications according to Clavien classification and 90-days mortality rates following ORC, LRC and RARC.
Reference
Year
90-days complication rate Clavien (%) Grade 1
Open RC series: Takada N. Shabsigh A. Novara G. Ramani V. Lavallée L. Novotny V. Isbarn H. Stimons C.J. Schiavina R. De Nunzio C. Chang S. S. Studer U. Lowrance W.T. Konety B.R. Rosario D.J. Madersbacher S. Hautmann R.E.
2012 2009 2009 2009 2014 2007 2009 2010 2013 2013 2002 2006 2008 2006 2000 2003 2010
23% 11% 6% ----------14.3% ---
Laparoscopic RC series: Moinzareh A.
2005
-----
Cathelineau X. Castillo P. Hemal A.K. Haber G.P. Park B. Albissini S. Huang J. Fontana P.P. Springer C. Gillion N. Aboumarzouk O.M.
2005 2006 2008 2007 2013 2015 2010 2015 2014 2010 2012
Robot-assisted RC series: Bochner B.H. 2015 Khan M.S. 2015 Novara G. 2015 Swentner C. 2015 Koupparis A. 2015 Sim A. 2015
---------
Grade 2 28% 40% 28% ----------20% --30.9% --38% ------36.1%
----14 events ----16.6% ----0 5 events 71 events 140 events 11 events 33 events 37.7% 49.1% 0 21.6% ----33.8% 6.1%
9% 11.9%
--25% 44.5% 24.2% 14% 15.8%
summarizes the results of these studies regarding perioperative outcomes and complications rates. Concerning perioperative outcomes, the data reported show how either LRC or RARC can offer a reduced expected blood loss and transfusion rates compared to ORC. Among minimally invasive approaches, RARC is associated with a higher blood loss compared to LRC but with an inferior transfusion rate. These data are in accordance with previous results from a large systematic review and meta-analysis of perioperative outcomes of RARC conducted by Novara et al., based on the revision of 70 surgical robotic case series and 23 comparative studies.5 When considering operative time, both RARC and LRC have longer operative times compared to ORC and between minimally invasive approaches RARC has the
90-days mortality rate
Grade 3
Grade 4
Grade 5
15% 12% 8% ----------9.1% ---
0.8% 0.2% 3% ----------1.2% ---
2% 2.7% 3% ----------4.4% --0.3% 1.7% 1.7% -------
4.9% ---
--7.4%
-------
------21.8%
-----
----1 event ----10.4% ----4 events 0 89 events 6 events 20 events --13.2% 0 0 0 ----0 0
6% 27.7%
13% 30% 15% 25.8% 1% 8.9%
------------0 10 events --1.9% 0 --4.6%
2% 2.7% 3% 0.4---13.5% 2.9% 0.8% 3.9% 6.9% 4.4% 1.7% 0.3% 1.7% 1.7% 2.57% 1.98% --2.3% 0 33.3% --3.3% 2% --0 2% 16.6% 1.9% ----4.6% --0 2.4%
2% 0
0.9% 0
longest. Even in high-volume centers with the most experienced surgeons in laparoscopy and robotic surgery, operative time remains higher than ORC. Overall mean in-hospital stay was 13.5 days in ORC, 11 in LRC, and 12.4 in RARC thus reflecting a somehow comparable time-lapse among the three approaches. This parameter, however, is full of possible misinterpretations as long as it is influenced by single hospital regulations. Some institutions, in fact, as a standard policy, admit patients one or two days before surgery, thus, modifying the interpretation of the in-hospital stay data. The re-admission rate was relatively under-reported in the analyzed papers, but its values were almost always >20%, thus reflecting a very high rate of second hospitalizations due to RC complications even in high-volume centers.
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8 Concerning post-operative complications, since 2002, recommendations exist on how to properly report on them. An ideal methodology for reporting adverse events related to surgical therapy should include 10 established basic reporting criteria11 : (1) a clear description of the method of data acquisition, (2) an indication of the duration of follow-up, (3) an indication of whether or not outpatient complication data are included, (4) definitions/inclusion criteria of at least one complication, (5) an indication of the mortality rate and cause of death, (6) an indication of the morbidity rate (number of patients and the total number of complications recorded), (7) an indication of procedurespecific complications, (8) the utilization of a grading system to clarify severity of complications, (9) an indication of the median or mean length of stay, and (10) an indication of the methodology utilized to assess patient risk stratification (e.g., Charlson-Romano index, ASA scoring). Despite that, many inhomogeneous reporting methods are still used in the literature, with a huge lack in information, which make comparison between the outcomes of different institutions, surgeons or surgical techniques almost impossible. Furthermore, as long as post-operative complications are also used as a surrogate of quality of surgery and care, other than surgical competency, the importance of standardizing the reporting method must be stressed and underlined. Shabsigh et al.12 in a large retrospective study defining early morbidity of RC found a 64% complication rate, which is much higher compared to other similar series.25 This difference is most probably due to differences in reporting data and in defining the type of complications rather than to a difference in surgical experience or technique. Few studies evaluated independent predictors of postoperative complications including multivariable analysis, and those are mainly in the ORC series. Chang et al.22 found ASA score, transfusion need, and intensive-care unit admission as predictive factors for high-grade complications. The same results regarding ASA score classification were also found in a large retrospective analysis from the Memorial Sloan Kettering Cancer Centre where Shabsigh et al.12 found as general predictors of post-operative mortality gender, ASA score, and the type of urinary diversion. Other predictive factors of mortality described are pathologic stage, histologic subtype, low pre-operative albumin level, operative time >6 h, and previous abdominal surgery.29---40 In the LRC series, there are no studies specifically analyzing independent predictors of perioperative outcomes and complications but both Castillo et al.31 and Haber et al.33 found a progressive reduction in complications and operative time with progressive case-load increase. On the other hand, Aboumarzouk et al.40 found no link with increased case-load and perioperative outcomes. In the RARC series, more interesting data come from three RCTs.7,41,42 In the first one, Bochner et al. randomized 58 patients to ORC vs 60 to RARC. The results of this randomized trial showed complication rates of 90 days after surgery, of 62% and 66% in the RARC and ORC arms, respectively, using an ITT analysis. At the mandated interim analysis of this protocol, the similarity in complication rates met the trial’s predetermined futility criteria and led to the early closure of the trial. This trial thus failed to demonstrate any significant beneficial effect on complications of RARC vs ORC. The second RCT is the CORAL trial where Khan et al.
A. Palazzetti et al. randomized patients into three arms: ORC, LRC, and RARC for the first time in the literature. The results of the CORAL trial are biased by the poor number of patients randomized, but nevertheless they fail to find a benefit in complication rate between ORC and RARC while, on the other hand, finding a significant advantage in the LRC arm. The third one, by Parekh et al.,42 randomizing 20 patients in the open arm and 20 in the robotic one also confirmed the same concepts. The results of a multicentric large phase three randomized controlled trial, the RAndomiZed Open vs Robotic cystectomy trial (RAZOR)8 are not awaited before 2016---2017. Finally, we can consider that major complications occur in the reconstructive part of radical cystectomy, which is performed extracorporally in the majority of the studies included. This data might explain why minimally invasive techniques show a benefit in terms of blood loss, which is prevalent in the demolition part of surgery, but not in terms of post-operative complications, which are mainly related to the diversion itself. Only a few institutions are now performing totally intracorporeal urinary diversion, and more comparative studies are needed to better conclude on this topic.
Conclusions Despite the efforts to reduce morbidity of RC, complication rates of minimally invasive approaches remain high. A trend toward high-grade complication rates of less than 90 days is seen with LRC and RARC. Laparoscopic radical cystectomy and RARC, moreover, offer less blood loss and transfusion rates compared to ORC. Operative time, however, remains longer even in high-volume centers compared to the standard open approach. Further studies are needed to clarify if minimally invasive surgery, either LRC or RARC, might show a real benefit over ORC and not just non-inferiority results.
Conflict of interest The authors declare that they have no conflict of interest.
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