# Comparing Robotic-Assisted to Open Radical Cystectomy in the Management of Non-Muscle-Invasive Bladder Cancer: A Propensity Score Matched-Pair Analysis

Etienne Courboin, Romain Mathieu, Valentina Panetta, Georges Mjaess, Romain Diamond, Gregory Verhoest, Mathieu Roumiguié, Anne Sophie Bajeot, Francesco Soria, Chiara Lonati, et al.

► To cite this version:

Etienne Courboin, Romain Mathieu, Valentina Panetta, Georges Mjaess, Romain Diamond, et al. Comparing Robotic-Assisted to Open Radical Cystectomy in the Management of Non-Muscle-Invasive Bladder Cancer: A Propensity Score Matched-Pair Analysis. Cancers, 2023, 15 (19), pp.4732. 10.3390/cancers15194732. hal-04284066

HAL Id: hal-04284066

https://univ-rennes.hal.science/hal-04284066

Submitted on 28 May 2024

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
# Comparing Robotic-Assisted to Open Radical Cystectomy in the Management of Non-Muscle-Invasive Bladder Cancer: A Propensity Score Matched-Pair Analysis

Etienne Courboin, Romain Mathieu, Valentina Panetta, Georges Mjaess, Romain Diamond, Gregory Verhoest, Mathieu Roumiguié, Anne Sophie Bajeot, Francesco Soria, Chiara Lonati, et al.

► To cite this version:

Etienne Courboin, Romain Mathieu, Valentina Panetta, Georges Mjaess, Romain Diamond, et al. Comparing Robotic-Assisted to Open Radical Cystectomy in the Management of Non-Muscle-Invasive Bladder Cancer: A Propensity Score Matched-Pair Analysis. Cancers, 2023, 15 (19), pp.4732. 10.3390/cancers15194732. hal-04284066

HAL Id: hal-04284066

https://univ-rennes.hal.science/hal-04284066v1

Submitted on 28 May 2024

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
Article

# Comparing Robotic-Assisted to Open Radical Cystectomy in the Management of Non-Muscle-Invasive Bladder Cancer: A Propensity Score Matched-Pair Analysis

Etienne Courboin <fnref n="1" />,<fnref n="2" />,*, Romain Mathieu <fnref n="2" />, Valentina Panetta <fnref n="3" />, Georges Mjaess <fnref n="1" />, Romain Diamond <fnref n="4" />, Gregory Verhoest <fnref n="2" />, Mathieu Roumiguié <fnref n="5" />, Anne Sophie Bajeot <fnref n="5" />, Francesco Soria <fnref n="6" />, Chiara Lonati <fnref n="7" />, Claudio Simeone <fnref n="7" />, Giuseppe Simone <fnref n="8" />, Umberto Anceschi <fnref n="8" />, Paolo Umari <fnref n="9" />, Ashwin Sridhar <fnref n="10" />, John Kelly <fnref n="10" />, Laura S. Mertens <fnref n="11" />, Rafael Sanchez-Salas <fnref n="12" />, Anna Colomer <fnref n="12" />, Maria Angela Cerruto <fnref n="13" />, Alessandro Antonelli <fnref n="13" />, Wojciech Krajewski <fnref n="14" />, Thierry Quackels <fnref n="1" />, Alexandre Peltier <fnref n="4" />, Francesco Montorsi <fnref n="15" />, Alberto Briganti <fnref n="15" />, Jeremy Y. C. Teoh <fnref n="16" />, Benjamin Pradere <fnref n="17" />,<fnref n="18" />, Marco Moschini <fnref n="15" />, Thierry Roumeguère <fnref n="1" />,<fnref n="4" /> and Simone Albisinni <fnref n="1" />,<fnref n="19" /> on behalf of the European Association of Urology-Young Academic Urologists (EAU-YAU), Urothelial Carcinoma Working Group

<figure><img src="image_2.png" /></figure>

check for
updates

**Citation:** Courboin, E.; Mathieu, R.; Panetta, V.; Mjaess, G.; Diamond, R.; Verhoest, G.; Roumiguié, M.; Bajeot, A.S.; Soria, F.; Lonati, C.; et al. Comparing Robotic-Assisted to Open Radical Cystectomy in the Management of Non-Muscle-Invasive Bladder Cancer: A Propensity Score Matched-Pair Analysis. *Cancers* **2023**, *15*, 4732. https://doi.org/10.3390/cancers15194732

Academic Editors: Cosimo De Nunzio and Aldo Brassetti

Received: 10 July 2023
Revised: 22 August 2023

Accepted: 3 September 2023

Published: 26 September 2023

<figure><img src="image_3.png" /></figure>

**Copyright:** © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).

**Simple Summary:** In this study, we analyzed 593 patients with NMIBC who underwent radical cystectomy via a robotic-assisted or open approach between 2015 and 2020. Patients with NMIBC who underwent RARC or ORC were matched 1:1 by age, sex, BMI, year of surgery and urinary

<footnote n="1">¹ Department of Urology, University Clinics of Brussels, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium; gmjaess@gmail.com (G.M.); thierry.quackels@erasme.ulb.ac.be (T.Q.); thierry.roumeguere@erasme.ulb.ac.be (T.R.); albisinni.s simone@gmail.com (S.A.)</footnote>

<footnote n="2">² Department of Urology, CHU Rennes, 35000 Rennes, France; romain.mathieu@chu-rennes.fr (R.M.); gregory.verhoest@chu-rennes.fr (G.V.)</footnote>

<footnote n="3">³ L'altrastatistica S.R.L., Consultancy & Training, Biostatistics Office, 00100 Rome, Italy; valentina.panetta@laltrastatistica.com</footnote>

<footnote n="4">⁴ Department of Urology, Institut Jules Bordet, Université Libre de Bruxelles, 1070 Brussels, Belgium; romain.diamand@bordet.be (R.D.); alexandre.peltier@bordet.be (A.P.)</footnote>

<footnote n="5">⁵ Department of Urology, Andrology and Renal Transplantation, CHU Rangueil, Paul-Sabatier University, 31000 Toulouse, France; roumiguié ниуieu@yahoo.fr (M.R.); anne-sophie_bajeot@hotmail.fr (A.S.B.)</footnote>

<footnote n="6">⁶ Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, 10024 Turin, Italy; soria.fra@gmail.com</footnote>

<footnote n="7">7 Department of Urology, Spedali Civili di Brescia, 25123 Brescia, Italy; chiara.lonati@libero.it (C.L.); csimeone@libero.it (C.S.)</footnote>

<footnote n="8">8 Department of Urology, Regina Elena National Cancer Institute, 00100 Rome, Italy; puldet@gmail.com (G.S.); umeerto.anceschi@ifo.gov.it (U.A.)</footnote>

<footnote n="9">9 Departement of Urology, Ospedale Maggiore della Carità di Novara, Università del Piemonte Orientale, 28100 Novarra, Italy; paoloumari@gmail.com</footnote>

<footnote n="10">10 Division of Surgery and Interventional Sciences, University College London, London WC1E 6BT, UK; ashwinsridhar19@gmail.com (A.S.); john.kelly@gmail.com (J.K.)</footnote>

<footnote n="11">11 Department of Urology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; ls.mertens@gmail.com</footnote>

<footnote n="12">12 Department of Urology, Institut Mutualiste Montsouris, 70123 Paris, France; raersas@gmail.com (R.S.-S.); a.colomer@gmail.com (A.C.)</footnote>

<footnote n="13">13 Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata, 37100 Verona, Italy; mariaangela.cerruto@univr.it (M.A.C.); alxanto@hotmail.com (A.A.)</footnote>

<footnote n="14">14 Department of Minimally Invasive and Robotic Urology, Wrocław Medical University, 50-556 Wrocław, Poland; krajwoj@gmail.com</footnote>

<footnote n="15">15 Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; montorsi.francesco@hsr.it (F.M.); briganti.alberto@hsr.it (A.B.); marco.moschini87@gmail.com (M.M.)</footnote>

<footnote n="16">16 S.H. Ho Urology Centre, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; jeremyteoh@surgery.cuhk.edu.hk</footnote>

<footnote n="17">17 Department of Urology, University of Vienna, 1010 Vienna, Austria; benjaminpradere@gmail.com</footnote>

<footnote n="18">18 Department of Urology, Hopital La Croix du Sud, 31000 Toulouse, France</footnote>

<footnote n="19">19 Urology Unit, Department of Surgical Sciences, Tor Vergata University Hospital, University of Rome Tor Vergata, 00100 Rome, Italy</footnote>

<footnote>* Correspondence: etienne.courboin@chu-rennes.fr</footnote>
Article

# Comparing Robotic-Assisted to Open Radical Cystectomy in the Management of Non-Muscle-Invasive Bladder Cancer: A Propensity Score Matched-Pair Analysis

Etienne Courboin <fnref n="1" />,<fnref n="2" />,*, Romain Mathieu <fnref n="2" />, Valentina Panetta <fnref n="3" />, Georges Mjaess <fnref n="1" />, Romain Diamond <fnref n="4" />, Gregory Verhoest <fnref n="2" />, Mathieu Roumiguié <fnref n="5" />, Anne Sophie Bajeot <fnref n="5" />, Francesco Soria <fnref n="6" />, Chiara Lonati <fnref n="7" />, Claudio Simeone <fnref n="7" />, Giuseppe Simone <fnref n="8" />, Umberto Anceschi <fnref n="8" />, Paolo Umari <fnref n="9" />, Ashwin Sridhar <fnref n="10" />, John Kelly <fnref n="10" />, Laura S. Mertens <fnref n="11" />, Rafael Sanchez-Salas <fnref n="12" />, Anna Colomer <fnref n="12" />, Maria Angela Cerruto <fnref n="13" />, Alessandro Antonelli <fnref n="13" />, Wojciech Krajewski <fnref n="14" />, Thierry Quackels <fnref n="1" />, Alexandre Peltier <fnref n="4" />, Francesco Montorsi <fnref n="15" />, Alberto Briganti <fnref n="15" />, Jeremy Y. C. Teoh <fnref n="16" />, Benjamin Pradere <fnref n="17" />,<fnref n="18" />, Marco Moschini <fnref n="15" />, Thierry Roumeguère <fnref n="1" />,<fnref n="4" /> and Simone Albisinni <fnref n="1" />,<fnref n="19" /> on behalf of the European Association of Urology-Young Academic Urologists (EAU-YAU), Urothelial Carcinoma Working Group

<figure><img src="image_2.png" /></figure>

check for
updates

**Citation:** Courboin, E.; Mathieu, R.; Panetta, V.; Mjaess, G.; Diamond, R.; Verhoest, G.; Roumiguié, M.; Bajeot, A.S.; Soria, F.; Lonati, C.; et al. Comparing Robotic-Assisted to Open Radical Cystectomy in the Management of Non-Muscle-Invasive Bladder Cancer: A Propensity Score Matched-Pair Analysis. *Cancers* **2023**, *15*, 4732. https://doi.org/10.3390/cancers15194732

Academic Editors: Cosimo De Nunzio and Aldo Brassetti

Received: 10 July 2023

Revised: 22 August 2023

Accepted: 3 September 2023

Published: 26 September 2023

<figure><img src="image_3.png" /></figure>

**Copyright:** © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).

**Simple Summary:** In this study, we analyzed 593 patients with NMIBC who underwent radical cystectomy via a robotic-assisted or open approach between 2015 and 2020. Patients with NMIBC who underwent RARC or ORC were matched 1:1 by age, sex, BMI, year of surgery and urinary

<footnote n="1">¹ Department of Urology, University Clinics of Brussels, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium; gmjaess@gmail.com (G.M.); thierry.quackels@erasme.ulb.ac.be (T.Q.); thierry.roumeguere@erasme.ulb.ac.be (T.R.); albisinni.s simone@gmail.com (S.A.)</footnote>

<footnote n="2">² Department of Urology, CHU Rennes, 35000 Rennes, France; romain.mathieu@chu-rennes.fr (R.M.); gregory.verhoest@chu-rennes.fr (G.V.)</footnote>

<footnote n="3">³ L'altrastatistica S.R.L., Consultancy & Training, Biostatistics Office, 00100 Rome, Italy; valentina.panetta@laltrastatistica.com</footnote>

<footnote n="4">⁴ Department of Urology, Institut Jules Bordet, Université Libre de Bruxelles, 1070 Brussels, Belgium; romain.diamand@bordet.be (R.D.); alexandre.peltier@bordet.be (A.P.)</footnote>

<footnote n="5">⁵ Department of Urology, Andrology and Renal Transplantation, CHU Rangueil, Paul-Sabatier University, 31000 Toulouse, France; roumiguié ниуieu@yahoo.fr (M.R.); anne-sophie_bajeot@hotmail.fr (A.S.B.)</footnote>

<footnote n="6">⁶ Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, 10024 Turin, Italy; soria.fra@gmail.com</footnote>

<footnote n="7">7 Department of Urology, Spedali Civili di Brescia, 25123 Brescia, Italy; chiara.lonati@libero.it (C.L.); csimeone@libero.it (C.S.)</footnote>

<footnote n="8">8 Department of Urology, Regina Elena National Cancer Institute, 00100 Rome, Italy; puldet@gmail.com (G.S.); umberto.anceschi@ifo.gov.it (U.A.)</footnote>

<footnote n="9">9 Departement of Urology, Ospedale Maggiore della Carità di Novara, Università del Piemonte Orientale, 28100 Novarra, Italy; paoloumari@gmail.com</footnote>

<footnote n="10">10 Division of Surgery and Interventional Sciences, University College London, London WC1E 6BT, UK; ashwinsridhar19@gmail.com (A.S.); john.kelly@gmail.com (J.K.)</footnote>

<footnote n="11">11 Department of Urology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; ls.mertens@gmail.com</footnote>

<footnote n="12">12 Department of Urology, Institut Mutualiste Montsouris, 70123 Paris, France; raersas@gmail.com (R.S.-S.); a.colomer@gmail.com (A.C.)</footnote>

<footnote n="13">13 Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata, 37100 Verona, Italy; mariaangela.cerruto@univr.it (M.A.C.); alxanto@hotmail.com (A.A.)</footnote>

<footnote n="14">14 Department of Minimally Invasive and Robotic Urology, Wrocław Medical University, 50-556 Wrocław, Poland; krajwoj@gmail.com</footnote>

<footnote n="15">15 Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; montorsi.francesco@hsr.it (F.M.); briganti.alberto@hsr.it (A.B.); marco.moschini87@gmail.com (M.M.)</footnote>

<footnote n="16">16 S.H. Ho Urology Centre, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; jeremyteoh@surgery.cuhk.edu.hk</footnote>

<footnote n="17">17 Department of Urology, University of Vienna, 1010 Vienna, Austria; benjaminpradere@gmail.com</footnote>

<footnote n="18">18 Department of Urology, Hopital La Croix du Sud, 31000 Toulouse, France</footnote>

<footnote n="19">19 Urology Unit, Department of Surgical Sciences, Tor Vergata University Hospital, University of Rome Tor Vergata, 00100 Rome, Italy</footnote>

<footnote>* Correspondence: etienne.courboin@chu-rennes.fr</footnote>
diversion. We found that RARC + ICUD for patients with NMIBC is safe and associated with a lower blood loss, a lower transfusion rate and a shorter hospital stay compared to ORC. Complication rates were similar. Concerning oncologic outcomes, RARC appeared non-inferior to ORC with no significant difference in DFS, CSS and OS. These results must be confirmed with prospective randomized studies.

**Abstract:** Background: For non-muscle-invasive bladder cancer (NMIBC) requiring radical surgery, limited data are available comparing robotic-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) to open radical cystectomy (ORC). The objective of this study was to compare the two surgical techniques. Methods: A multicentric cohort of 593 patients with NMIBC undergoing iRARC or ORC between 2015 and 2020 was prospectively gathered. Perioperative and pathologic outcomes were compared. Results: A total of 143 patients operated on via iRARC were matched to 143 ORC patients. Operative time was longer in the iRARC group (p = 0.034). Blood loss was higher in the ORC group (p < 0.001), with a consequent increased post-operative transfusion rate in the ORC group (p = 0.003). Length of stay was longer in the ORC group (p = 0.007). Post-operative complications did not differ significantly (all p > 0.05). DFS at 60 months was 55.9% in ORC and 75.2% in iRARC with a statistically significant difference (p = 0.033) found in the univariate analysis. Conclusion: We found that iRARC for patients with NMIBC is safe, associated with a lower blood loss, a lower transfusion rate and a shorter hospital stay compared to ORC. Complication rates were similar. No significant differences in survival analyses emerged across the two techniques.

**Keywords:** cystectomy; non-muscle-invasive bladder cancer; robotic-assisted radical cystectomy; open radical cystectomy; intracorporeal urinary diversion

# 1. Introduction

Non-muscle-invasive bladder cancer (NMIBC) accounts for 75% of bladder cancer cases [1]. Although most patients are treated with conservative therapy, radical cystectomy (RC) is recommended for NMIBC with aggressive features such as high-risk patients, very high-risk patients or patients not responsive to BCG therapy [2]. However, RC is associated with high rates of morbidity and non-negligeable mortality [3]. Robotic-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) is surging worldwide in the effort to reduce morbidity [4]. Retrospective series and RCTs reported shorter lengths of hospital stays and reduced transfusions after RARC compared to open radical cystectomy (ORC) [5]. Nonetheless, no significant difference in post-operative complications have been demonstrated, whereas oncologic outcomes appear comparable [6-8].

While most studies comparing iRARC to ORC mainly included patients with muscle-invasive bladder cancer, no study specifically compared ORC to iRARC for NMIBC. Patients with NMIBC differ from MIBC: the tumor is theoretically strictly organ-confined, leading to a different therapeutic management even when a cystectomy is indicated. Neoadjuvant systemic therapies are not recommended for NMIBC, which exhibits a better general condition at time of surgery. The absence of an invasive tumor may lead to a more conservative treatment with organ sparing and less extended lymph node dissection [9]. Finally, NMIBC in progression to MIBC may have a worse prognosis than de novo MIBC [10].

The objective of our study is to compare the perioperative outcomes of iRARC and ORC in a multicentric cohort of patients with NMIBC using a propensity score matched-pair analysis. Furthermore, we sought to explore oncologic outcomes across the two surgical techniques for NMIBC.
diversion. We found that RARC + ICUD for patients with NMIBC is safe and associated with a lower blood loss, a lower transfusion rate and a shorter hospital stay compared to ORC. Complication rates were similar. Concerning oncologic outcomes, RARC appeared non-inferior to ORC with no significant difference in DFS, CSS and OS. These results must be confirmed with prospective randomized studies.

**Abstract:** Background: For non-muscle-invasive bladder cancer (NMIBC) requiring radical surgery, limited data are available comparing robotic-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) to open radical cystectomy (ORC). The objective of this study was to compare the two surgical techniques. Methods: A multicentric cohort of 593 patients with NMIBC undergoing iRARC or ORC between 2015 and 2020 was prospectively gathered. Perioperative and pathologic outcomes were compared. Results: A total of 143 patients operated on via iRARC were matched to 143 ORC patients. Operative time was longer in the iRARC group (p = 0.034). Blood loss was higher in the ORC group (p < 0.001), with a consequent increased post-operative transfusion rate in the ORC group (p = 0.003). Length of stay was longer in the ORC group (p = 0.007). Post-operative complications did not differ significantly (all p > 0.05). DFS at 60 months was 55.9% in ORC and 75.2% in iRARC with a statistically significant difference (p = 0.033) found in the univariate analysis. Conclusion: We found that iRARC for patients with NMIBC is safe, associated with a lower blood loss, a lower transfusion rate and a shorter hospital stay compared to ORC. Complication rates were similar. No significant differences in survival analyses emerged across the two techniques.

**Keywords:** cystectomy; non-muscle-invasive bladder cancer; robotic-assisted radical cystectomy; open radical cystectomy; intracorporeal urinary diversion

# 1. Introduction

Non-muscle-invasive bladder cancer (NMIBC) accounts for 75% of bladder cancer cases [1]. Although most patients are treated with conservative therapy, radical cystectomy (RC) is recommended for NMIBC with aggressive features such as high-risk patients, very high-risk patients or patients not responsive to BCG therapy [2]. However, RC is associated with high rates of morbidity and non-negligeable mortality [3]. Robotic-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) is surging worldwide in the effort to reduce morbidity [4]. Retrospective series and RCTs reported shorter lengths of hospital stays and reduced transfusions after RARC compared to open radical cystectomy (ORC) [5]. Nonetheless, no significant difference in post-operative complications have been demonstrated, whereas oncologic outcomes appear comparable [6-8].

While most studies comparing iRARC to ORC mainly included patients with muscle-invasive bladder cancer, no study specifically compared ORC to iRARC for NMIBC. Patients with NMIBC differ from MIBC: the tumor is theoretically strictly organ-confined, leading to a different therapeutic management even when a cystectomy is indicated. Neoadjuvant systemic therapies are not recommended for NMIBC, which exhibits a better general condition at time of surgery. The absence of an invasive tumor may lead to a more conservative treatment with organ sparing and less extended lymph node dissection [9]. Finally, NMIBC in progression to MIBC may have a worse prognosis than de novo MIBC [10].

The objective of our study is to compare the perioperative outcomes of iRARC and ORC in a multicentric cohort of patients with NMIBC using a propensity score matched-pair analysis. Furthermore, we sought to explore oncologic outcomes across the two surgical techniques for NMIBC.
## 2. Materials and Methods

### 2.1. *Study Design and Data*

A multicentric database of patients undergoing RC was created by the European Association of Urology-Young Academic Urologists (EAU-YAU), Urothelial Carcinoma Working Group. This multicentric cohort included patients undergoing either iRARC or ORC between 2014 and 2021. Only centers that maintained a local prospective registry of patients undergoing RC were invited to participate and they provided ethic committee and institutional review board approval. Twenty-three centers participated in the study. We then selected patients undergoing RC for high-risk and very high-risk NMIBC defined as T1 high grade (HG) associated with concomitant bladder carcinoma in situ (CIS), multiple and/or large T1HG and/or recurrent T1HG, or NMIBC that did not respond to BCG therapy defined as BCG-refractory tumor, BCG-unresponsive or BCG-relapsing [2]. This study was approved by the CNIL (Comité National Informatique et Liberté) and was conducted following the principles of the Helsinki Declaration.

### 2.2. *Surgery and Perioperative Work-Up*

No bowel preparation was performed prior to surgery. In the iRARC group, all urinary diversions were performed intracorporeally. All centers implemented an ERAS protocol [11]; early mobilization and oral feeding was encouraged for all patients. Low-molecular weight heparin was prescribed for four weeks following guidelines. Ureteral catheters were removed on POD 7-14 and urethral catheters (in case of neobladder) on POD 10-21. Complications were graded using the Clavien-Dindo classification (CDC) [12] and comprehensive complication index (CCI) [13]. The comprehensive complication index was calculated using an online tool (assesssurgery.com (accessed on 20 January 2023)). For follow-up, patients were seen at one month post-surgery, every three months the first year, twice a year the second year, then annually.

### 2.3. *Statistical Analysis*

A total of 593 patients with NMIBC were available for analysis, with 409 open and 184 robotic. The propensity score was estimated using a multivariable logistic regression model. The model included the following variables: year of operation, age, sex, BMI urinary diversion in 3 classes and ASA score. After setting a caliper width of 0.25 standard deviations of the propensity score, cases were matched to controls without replacement to the closest matched propensity score with a 1:1 ratio. The standardized mean difference was used to evaluate balancing between ORC and RARC, with STD ≤ 0.1 considered to be a good balance. To take into account the matching outcome, analyses were made using robust-clustered standard errors.

Linear regression with robust-clustered standard errors (matching) was used to evaluate continuous outcomes such as operating time and blood loss. In the case of blood loss, the logarithm of the original value was used as a dependent variable and the geometric mean and SD were presented. Beta coefficients (B) and their 95% CI were reported. Logistic regression with robust clustered standard errors (matching) was used to evaluate the dichotomous outcome of either the presence of a transfusion or the presence of a complication. Odds ratios (ORs) with 95% CIs were reported. Poisson regression with robust clustered standard errors (matching) was used to evaluate quantitative outcomes such as the number of transfusions, number of complications and length of stay. Incidence rate ratios (IRRs) with 95% CIs were reported. The Mann-Whitney test was used to compare pT and pN distribution between the two groups. χ2 test was used to compare positive margins and CIS between the two groups. Kaplan-Meier curves were performed to evaluate disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). Cox regression robust clustered standard errors were examined to compare the two groups. Proportional assumptions were tested. A multivariable Cox regression was implemented, adding pT as independent variables. Hazard ratios (HRs) with 95% CIs were reported. A *p*-value
## 2. Materials and Methods

### 2.1. *Study Design and Data*

A multicentric database of patients undergoing RC was created by the European Association of Urology-Young Academic Urologists (EAU-YAU), Urothelial Carcinoma Working Group. This multicentric cohort included patients undergoing either iRARC or ORC between 2014 and 2021. Only centers that maintained a local prospective registry of patients undergoing RC were invited to participate and they provided ethic committee and institutional review board approval. Twenty-three centers participated in the study. We then selected patients undergoing RC for high-risk and very high-risk NMIBC defined as T1 high grade (HG) associated with concomitant bladder carcinoma in situ (CIS), multiple and/or large T1HG and/or recurrent T1HG, or NMIBC that did not respond to BCG therapy defined as BCG-refractory tumor, BCG-unresponsive or BCG-relapsing [2]. This study was approved by the CNIL (Comité National Informatique et Liberté) and was conducted following the principles of the Helsinki Declaration.

### 2.2. *Surgery and Perioperative Work-Up*

No bowel preparation was performed prior to surgery. In the iRARC group, all urinary diversions were performed intracorporeally. All centers implemented an ERAS protocol [11]; early mobilization and oral feeding was encouraged for all patients. Low-molecular weight heparin was prescribed for four weeks following guidelines. Ureteral catheters were removed on POD 7-14 and urethral catheters (in case of neobladder) on POD 10-21. Complications were graded using the Clavien-Dindo classification (CDC) [12] and comprehensive complication index (CCI) [13]. The comprehensive complication index was calculated using an online tool (assesssurgery.com (accessed on 20 January 2023)). For follow-up, patients were seen at one month post-surgery, every three months the first year, twice a year the second year, then annually.

### 2.3. *Statistical Analysis*

A total of 593 patients with NMIBC were available for analysis, with 409 open and 184 robotic. The propensity score was estimated using a multivariable logistic regression model. The model included the following variables: year of operation, age, sex, BMI urinary diversion in 3 classes and ASA score. After setting a caliper width of 0.25 standard deviations of the propensity score, cases were matched to controls without replacement to the closest matched propensity score with a 1:1 ratio. The standardized mean difference was used to evaluate balancing between ORC and RARC, with STD ≤ 0.1 considered to be a good balance. To take into account the matching outcome, analyses were made using robust-clustered standard errors.

Linear regression with robust-clustered standard errors (matching) was used to evaluate continuous outcomes such as operating time and blood loss. In the case of blood loss, the logarithm of the original value was used as a dependent variable and the geometric mean and SD were presented. Beta coefficients (B) and their 95% CI were reported. Logistic regression with robust clustered standard errors (matching) was used to evaluate the dichotomous outcome of either the presence of a transfusion or the presence of a complication. Odds ratios (ORs) with 95% CIs were reported. Poisson regression with robust clustered standard errors (matching) was used to evaluate quantitative outcomes such as the number of transfusions, number of complications and length of stay. Incidence rate ratios (IRRs) with 95% CIs were reported. The Mann-Whitney test was used to compare pT and pN distribution between the two groups. χ2 test was used to compare positive margins and CIS between the two groups. Kaplan-Meier curves were performed to evaluate disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). Cox regression robust clustered standard errors were examined to compare the two groups. Proportional assumptions were tested. A multivariable Cox regression was implemented, adding pT as independent variables. Hazard ratios (HRs) with 95% CIs were reported. A *p*-value
of <0.05 was considered statistically significant. Statistical analysis was performed with STATA 16.1.

### 3. Results

A total of 143 patients operated on via iRARC were matched to 143 open cases. Table 1 shows no statistically significant difference across the two groups after propensity score matching. The stage at TURBT was comparable across the two groups (open, cT1 = 123/143 (86%), robot 126/143 (88%), *p* = 0.60), as well as the presence of CIS on TUR-BT specimens (open, CIS = 52/143 (36%), robot 58/143 (41%), *p* = 0.47). The number of patients having received previous intravesical treatment was not statistically different across the two groups (78/143, 55% patients in ORC group vs. 73/143, 51% patients in RARC group, *p* = 0.74).

<table><caption>**Table 1.** Baseline patient characteristics before and after matching.</caption><thead><tr><th rowspan="2"></th><th rowspan="2"></th><th colspan="4">Before Propensity Score Matching</th><th colspan="4">After Propensity Score Matching</th></tr><tr><th>ORC<br>(n = 366)</th><th>RARC<br>(n = 184)</th><th>STD</th><th>p Value</th><th>ORC<br>(n = 143)</th><th>RARC<br>(n = 143)</th><th>STD</th><th>p Value</th></tr></thead><tbody><tr><td>Age (years)</td><td>mean (sd)</td><td>70.9 (8.4)</td><td>64.0 (10.0)</td><td>-0.73</td><td>&lt;0.001</td><td>66.8 (8.9)</td><td>67.3 (7.6)</td><td>0.06</td><td>0.597</td></tr><tr><td>Male sex</td><td>n (%)</td><td>292 (79.8)</td><td>164 (89.1)</td><td>-0.26</td><td>0.006</td><td>122 (85.3)</td><td>128 (86.0)</td><td>-0.02</td><td>0.866</td></tr><tr><td>Urinary diversion</td><td></td><td></td><td></td><td></td><td>&lt;0.001</td><td></td><td></td><td></td><td>0.909</td></tr><tr><td>Orthotopic<br>neobladder</td><td>n (%)</td><td>75 (20.2)</td><td>94 (51.1)</td><td>0.57</td><td></td><td>62 (43.4)</td><td>59 (41.3)</td><td>-0.04</td><td></td></tr><tr><td>Ileal conduit</td><td>n (%)</td><td>224 (61.2)</td><td>84 (45.7)</td><td>-0.31</td><td></td><td>76 (53.2)</td><td>78 (54.6)</td><td>0.03</td><td></td></tr><tr><td>Ureterocutaneostomy</td><td>n (%)</td><td>67 (18.3)</td><td>6 (3.3)</td><td>-0.50</td><td></td><td>5 (23.5)</td><td>6 (4.2)</td><td>0.04</td><td></td></tr><tr><td>ASA 3-4</td><td>n (%)</td><td>180 (49.2)</td><td>61 (33.2)</td><td>-0.33</td><td>&lt;0.001</td><td>53 (37.1)</td><td>54 (37.8)</td><td>0.01</td><td>0.903</td></tr><tr><td>Year of surgery</td><td></td><td></td><td></td><td></td><td>&lt;0.001</td><td></td><td></td><td></td><td>0.612</td></tr><tr><td>2015-2016</td><td>n (%)</td><td>105 (28.7)</td><td>48 (26.1)</td><td>-0.06</td><td></td><td>40 (28.0)</td><td>39 (27.3)</td><td>-0.02</td><td></td></tr><tr><td>2017-2018</td><td>n (%)</td><td>147 (40.2)</td><td>41 (22.3)</td><td>-0.39</td><td></td><td>31 (21.7)</td><td>38 (26.6)</td><td>0.11</td><td></td></tr><tr><td>2019-2020</td><td>n (%)</td><td>114 (31.2)</td><td>95 (51.6)</td><td>0.42</td><td></td><td>72 (50.4)</td><td>66 (46.2)</td><td>-0.08</td><td></td></tr><tr><td>BMI (kg/m²)</td><td>mean (sd)</td><td>26.0 (4.3)</td><td>26.1 (4.2)</td><td>0.03</td><td>0.705</td><td>26.1 (5.0)</td><td>26.3 (4.4)</td><td>0.04</td><td>0.732</td></tr></tbody></table>

Table 2 illustrates perioperative results. Operative time was significantly longer in the iRARC group (309 min vs. 288 min, *p* = 0.034). Estimated blood loss was significantly higher in the open group (471 mL vs. 279 mL, *p* < 0.001), and consequently a higher post-operative transfusion rate was observed in the open group: 29 patients (20.3%) vs. 14 patients (9.8%), *p* = 0.003. Mean length of stay was 13.7 days in the RARC group vs. 17.2 days in the ORC group, *p* = 0.007.

Concerning post-operative complications, we found no significant difference across the two groups. Similarly, early readmissions were comparable (Table 2). We found 17% for major complications in both groups; although lower in the RARC group, the comprehensive complication index did not differ significantly across the two surgical techniques. No significant difference was found in hemoglobin (*p* = 0.17) or creatinine (*p* = 0.59) change.

On final pathology (Table 3), 34.3% had muscle-invasive disease in the ORC vs. 24.5% in the RARC group (*p* = 0.069). The mean LN removed was similar between the two groups. A similar rate of lymph node-positive patients was found within the two groups (13/143 ORC vs. 15/143 RARC, *p* = 0.77). In linear regression, the number of resected lymph nodes significantly correlated to operative time (B = 1.12, 95% CI: 0.28; 1.96, *p* = 0.009). On the other hand, the number of lymph nodes did not influence blood loss (B = -0.001, 95% CI: -0.006; 0.003, *p* = 0.501) and the difference between iRARC and ORC for blood loss remained significant even when corrected for the number of lymph nodes (B = -0.23, 95% CI: -0.3; -0.1, *p* < 0.001). Estimated blood loss also increased with increasing pT stages (B = 0.04, 95% CI: 0.01; 0.06, *p* = 0.003). However, the reduced estimated blood loss observed in the iRARC group is confirmed in each pT subgroup (B = -0.22, 95% CI: -0.3; -0.1, *p* < 0.001).
of <0.05 was considered statistically significant. Statistical analysis was performed with STATA 16.1.

### 3. Results

A total of 143 patients operated on via iRARC were matched to 143 open cases. Table 1 shows no statistically significant difference across the two groups after propensity score matching. The stage at TURBT was comparable across the two groups (open, cT1 = 123/143 (86%), robot 126/143 (88%), *p* = 0.60), as well as the presence of CIS on TUR-BT specimens (open, CIS = 52/143 (36%), robot 58/143 (41%), *p* = 0.47). The number of patients having received previous intravesical treatment was not statistically different across the two groups (78/143, 55% patients in ORC group vs. 73/143, 51% patients in RARC group, *p* = 0.74).

<table><caption>**Table 1.** Baseline patient characteristics before and after matching.</caption><thead><tr><th rowspan="2"></th><th rowspan="2"></th><th colspan="4">Before Propensity Score Matching</th><th colspan="4">After Propensity Score Matching</th></tr><tr><th>ORC<br>(n = 366)</th><th>RARC<br>(n = 184)</th><th>STD</th><th>p Value</th><th>ORC<br>(n = 143)</th><th>RARC<br>(n = 143)</th><th>STD</th><th>p Value</th></tr></thead><tbody><tr><td>Age (years)</td><td>mean (sd)</td><td>70.9 (8.4)</td><td>64.0 (10.0)</td><td>-0.73</td><td>&lt;0.001</td><td>66.8 (8.9)</td><td>67.3 (7.6)</td><td>0.06</td><td>0.597</td></tr><tr><td>Male sex</td><td>n (%)</td><td>292 (79.8)</td><td>164 (89.1)</td><td>-0.26</td><td>0.006</td><td>122 (85.3)</td><td>128 (86.0)</td><td>-0.02</td><td>0.866</td></tr><tr><td>Urinary diversion</td><td></td><td></td><td></td><td></td><td>&lt;0.001</td><td></td><td></td><td></td><td>0.909</td></tr><tr><td>Orthotopic<br>neobladder</td><td>n (%)</td><td>75 (20.2)</td><td>94 (51.1)</td><td>0.57</td><td></td><td>62 (43.4)</td><td>59 (41.3)</td><td>-0.04</td><td></td></tr><tr><td>Ileal conduit</td><td>n (%)</td><td>224 (61.2)</td><td>84 (45.7)</td><td>-0.31</td><td></td><td>76 (53.2)</td><td>78 (54.6)</td><td>0.03</td><td></td></tr><tr><td>Ureterocutaneostomy</td><td>n (%)</td><td>67 (18.3)</td><td>6 (3.3)</td><td>-0.50</td><td></td><td>5 (23.5)</td><td>6 (4.2)</td><td>0.04</td><td></td></tr><tr><td>ASA 3-4</td><td>n (%)</td><td>180 (49.2)</td><td>61 (33.2)</td><td>-0.33</td><td>&lt;0.001</td><td>53 (37.1)</td><td>54 (37.8)</td><td>0.01</td><td>0.903</td></tr><tr><td>Year of surgery</td><td></td><td></td><td></td><td></td><td>&lt;0.001</td><td></td><td></td><td></td><td>0.612</td></tr><tr><td>2015-2016</td><td>n (%)</td><td>105 (28.7)</td><td>48 (26.1)</td><td>-0.06</td><td></td><td>40 (28.0)</td><td>39 (27.3)</td><td>-0.02</td><td></td></tr><tr><td>2017-2018</td><td>n (%)</td><td>147 (40.2)</td><td>41 (22.3)</td><td>-0.39</td><td></td><td>31 (21.7)</td><td>38 (26.6)</td><td>0.11</td><td></td></tr><tr><td>2019-2020</td><td>n (%)</td><td>114 (31.2)</td><td>95 (51.6)</td><td>0.42</td><td></td><td>72 (50.4)</td><td>66 (46.2)</td><td>-0.08</td><td></td></tr><tr><td>BMI (kg/m²)</td><td>mean (sd)</td><td>26.0 (4.3)</td><td>26.1 (4.2)</td><td>0.03</td><td>0.705</td><td>26.1 (5.0)</td><td>26.3 (4.4)</td><td>0.04</td><td>0.732</td></tr></tbody></table>

Table 2 illustrates perioperative results. Operative time was significantly longer in the iRARC group (309 min vs. 288 min, *p* = 0.034). Estimated blood loss was significantly higher in the open group (471 mL vs. 279 mL, *p* < 0.001), and consequently a higher post-operative transfusion rate was observed in the open group: 29 patients (20.3%) vs. 14 patients (9.8%), *p* = 0.003. Mean length of stay was 13.7 days in the RARC group vs. 17.2 days in the ORC group, *p* = 0.007.

Concerning post-operative complications, we found no significant difference across the two groups. Similarly, early readmissions were comparable (Table 2). We found 17% for major complications in both groups; although lower in the RARC group, the comprehensive complication index did not differ significantly across the two surgical techniques. No significant difference was found in hemoglobin (*p* = 0.17) or creatinine (*p* = 0.59) change.

On final pathology (Table 3), 34.3% had muscle-invasive disease in the ORC vs. 24.5% in the RARC group (*p* = 0.069). The mean LN removed was similar between the two groups. A similar rate of lymph node-positive patients was found within the two groups (13/143 ORC vs. 15/143 RARC, *p* = 0.77). In linear regression, the number of resected lymph nodes significantly correlated to operative time (B = 1.12, 95% CI: 0.28; 1.96, *p* = 0.009). On the other hand, the number of lymph nodes did not influence blood loss (B = -0.001, 95% CI: -0.006; 0.003, *p* = 0.501) and the difference between iRARC and ORC for blood loss remained significant even when corrected for the number of lymph nodes (B = -0.23, 95% CI: -0.3; -0.1, *p* < 0.001). Estimated blood loss also increased with increasing pT stages (B = 0.04, 95% CI: 0.01; 0.06, *p* = 0.003). However, the reduced estimated blood loss observed in the iRARC group is confirmed in each pT subgroup (B = -0.22, 95% CI: -0.3; -0.1, *p* < 0.001).
<table><caption>**Table 2.** Perioperative outcomes, complications and pathological stage.</caption><thead><tr><th></th><th></th><th>ORC (n = 143)</th><th>RARC (n = 143)</th><th></th><th>RARC vs. ORC</th><th>p</th></tr></thead><tbody><tr><td>Operative time (min)</td><td>Mean (SD)</td><td>287.5 (76.6)</td><td>308.7 (83.3)</td><td>B * (95% CI)</td><td>21.12 (1.63; 40.62)</td><td>0.034</td></tr><tr><td>Blood loss (mL)</td><td>Mean (SD)</td><td>471.4 (2.0)</td><td>279.2 (2.6)</td><td>B * (95% CI)</td><td>-0.23 (-0.33; -0.13)</td><td>&lt;0.001</td></tr><tr><td></td><td>Median (IQR)</td><td>500 (350-650)</td><td>300 (150-585)</td><td></td><td></td><td></td></tr><tr><td>Intraoperative transfusion</td><td>n (%)</td><td>19 (13.3)</td><td>14 (9.8)</td><td>OR ^ (95% CI)</td><td>0.71 (0.36; 1.40)</td><td>0.32</td></tr><tr><td>N of transfusions</td><td>Mean (SD)</td><td>1.9 (1.1)</td><td>2 (0.7)</td><td>irr ° (95% CI)</td><td>1.03 (0.76; 1.39)</td><td>0.863</td></tr><tr><td></td><td>Median (IQR)</td><td>2 (1-2)</td><td>2 (2-2)</td><td></td><td></td><td></td></tr><tr><td>Length of stay (days)</td><td>Mean (SD)</td><td>17.2 (12.7)</td><td>13.7 (9.0)</td><td>irr ° (95% CI)</td><td>0.80 (0.68; 0.94)</td><td>0.007</td></tr><tr><td></td><td>Median (IQR)</td><td>14 (9-20)</td><td>11 (8-16)</td><td></td><td></td><td></td></tr><tr><td>Post-operative transfusion</td><td>n (%)</td><td>29 (20.3)</td><td>14 (9.8)</td><td>OR ^ (95% CI)</td><td>0.32 (0.15; 0.68)</td><td>0.003</td></tr><tr><td>N of transfusions</td><td>Mean (SD)</td><td>2.3 (1.1)</td><td>3.2 (2.8)</td><td>irr ° (95% CI)</td><td>1.37 (0.86; 2.19)</td><td>0.188</td></tr><tr><td></td><td>Median (IQR)</td><td>2 (2-3)</td><td>2 (2-3)</td><td></td><td></td><td></td></tr><tr><td>Early Complications</td><td>n (%)</td><td>85 (59.4)</td><td>74 (51.8)</td><td>OR ^ (95% CI)</td><td>0.73 (0.5; 1.2)</td><td>0.199</td></tr><tr><td>Clavien-Major</td><td>n (%)</td><td>24 (16.8)</td><td>25 (17.5)</td><td>OR ^ (95% CI)</td><td>1.30 (0.7; 2.5)</td><td>0.448</td></tr><tr><td>Early Readmission</td><td>n (%)</td><td>14 (9.8)</td><td>16 (11.2)</td><td>OR ^ (95% CI)</td><td>1.16 (0.5; 2.5)</td><td>0.707</td></tr><tr><td>Comprehensive Complication Index 0-30 days</td><td>Mean (SD)</td><td>17.0 +/- 19.7</td><td>14.6 +/- 17.7</td><td>B * (95% CI)</td><td>-1.20 (-3.38; 0.97)</td><td>0.36</td></tr><tr><td></td><td>Median (IQR)</td><td>20.6 (0-24.2)</td><td>8.7 (0-24.5)</td><td></td><td></td><td></td></tr><tr><td>Late Complications</td><td>n (%)</td><td>28 (19.6)</td><td>23 (16.1)</td><td>OR ^ (95% CI)</td><td>0.79 (0.4; 1.5)</td><td>0.448</td></tr><tr><td>Clavien-Major</td><td>n (%)</td><td>12 (8.4)</td><td>12 (8.4)</td><td>OR ^ (95% CI)</td><td>1.5 (0.5; 4.4)</td><td>0.511</td></tr><tr><td>Late Readmission</td><td>n (%)</td><td>19 (13.3)</td><td>20 (14.0)</td><td>OR ^ (95% CI)</td><td>0.75 (0.4; 1.5)</td><td>0.398</td></tr><tr><td>Comprehensive Complication Index 0-90 days</td><td>Mean (SD)</td><td>20.4 (20.6)</td><td>17.4 +/- 20.8</td><td>B * (95% CI)</td><td>-1.50 (-3.91; 0.91)</td><td>0.16</td></tr><tr><td></td><td>Median (IQR)</td><td>20.6 (0-29.6)</td><td>20.6 (0-29.6)</td><td></td><td></td><td></td></tr><tr><td>Creatinine (mg/L)</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Pre-operative</td><td>Mean (SD)</td><td>1.1 (0.6)</td><td>1.0 (0.3)</td><td></td><td></td><td>0.081</td></tr><tr><td>Post-operative</td><td>Mean (SD)</td><td>1.1 (0.4)</td><td>0.9 (0.3)</td><td></td><td></td><td>0.007</td></tr><tr><td>Delta (Δ)</td><td>Mean (SD)</td><td>0.0 (0.4)</td><td>-0.0 (0.3)</td><td></td><td></td><td>0.59</td></tr><tr><td>Hemoglobin (g/dL)</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Pre-operative</td><td>Mean (SD)</td><td>13.5 (2.0)</td><td>13.4 (1.9)</td><td></td><td></td><td>0.814</td></tr><tr><td>Post-operative</td><td>Mean (SD)</td><td>10.6 (1.3)</td><td>10.9 (1.4)</td><td></td><td></td><td>0.130</td></tr><tr><td>Delta (Δ)</td><td>Mean (SD)</td><td>-2.9 (1.9)</td><td>-2.6 (1.7)</td><td></td><td></td><td>0.170</td></tr><tr><td>pT stage</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>pT0</td><td></td><td>25</td><td>17.5</td><td>15</td><td>10.5</td><td>0.351</td></tr><tr><td>pTa-pTis-pT1</td><td></td><td>69</td><td>48.3</td><td>93</td><td>65.0</td><td></td></tr><tr><td>pT2</td><td></td><td>14</td><td>9.8</td><td>14</td><td>9.8</td><td></td></tr><tr><td>pT3-4</td><td></td><td>35</td><td>24.5</td><td>21</td><td>14.7</td><td></td></tr></tbody></table>
<table><caption>**Table 2.** Perioperative outcomes, complications and pathological stage.</caption><thead><tr><th></th><th></th><th>ORC (n = 143)</th><th>RARC (n = 143)</th><th></th><th>RARC vs. ORC</th><th>p</th></tr></thead><tbody><tr><td>Operative time (min)</td><td>Mean (SD)</td><td>287.5 (76.6)</td><td>308.7 (83.3)</td><td>B * (95% CI)</td><td>21.12 (1.63; 40.62)</td><td>0.034</td></tr><tr><td>Blood loss (mL)</td><td>Mean (SD)</td><td>471.4 (2.0)</td><td>279.2 (2.6)</td><td>B * (95% CI)</td><td>-0.23 (-0.33; -0.13)</td><td>&lt;0.001</td></tr><tr><td></td><td>Median (IQR)</td><td>500 (350-650)</td><td>300 (150-585)</td><td></td><td></td><td></td></tr><tr><td>Intraoperative transfusion</td><td>n (%)</td><td>19 (13.3)</td><td>14 (9.8)</td><td>OR ^ (95% CI)</td><td>0.71 (0.36; 1.40)</td><td>0.32</td></tr><tr><td>N of transfusions</td><td>Mean (SD)</td><td>1.9 (1.1)</td><td>2 (0.7)</td><td>irr ° (95% CI)</td><td>1.03 (0.76; 1.39)</td><td>0.863</td></tr><tr><td></td><td>Median (IQR)</td><td>2 (1-2)</td><td>2 (2-2)</td><td></td><td></td><td></td></tr><tr><td>Length of stay (days)</td><td>Mean (SD)</td><td>17.2 (12.7)</td><td>13.7 (9.0)</td><td>irr ° (95% CI)</td><td>0.80 (0.68; 0.94)</td><td>0.007</td></tr><tr><td></td><td>Median (IQR)</td><td>14 (9-20)</td><td>11 (8-16)</td><td></td><td></td><td></td></tr><tr><td>Post-operative transfusion</td><td>n (%)</td><td>29 (20.3)</td><td>14 (9.8)</td><td>OR ^ (95% CI)</td><td>0.32 (0.15; 0.68)</td><td>0.003</td></tr><tr><td>N of transfusions</td><td>Mean (SD)</td><td>2.3 (1.1)</td><td>3.2 (2.8)</td><td>irr ° (95% CI)</td><td>1.37 (0.86; 2.19)</td><td>0.188</td></tr><tr><td></td><td>Median (IQR)</td><td>2 (2-3)</td><td>2 (2-3)</td><td></td><td></td><td></td></tr><tr><td>Early Complications</td><td>n (%)</td><td>85 (59.4)</td><td>74 (51.8)</td><td>OR ^ (95% CI)</td><td>0.73 (0.5; 1.2)</td><td>0.199</td></tr><tr><td>Clavien-Major</td><td>n (%)</td><td>24 (16.8)</td><td>25 (17.5)</td><td>OR ^ (95% CI)</td><td>1.30 (0.7; 2.5)</td><td>0.448</td></tr><tr><td>Early Readmission</td><td>n (%)</td><td>14 (9.8)</td><td>16 (11.2)</td><td>OR ^ (95% CI)</td><td>1.16 (0.5; 2.5)</td><td>0.707</td></tr><tr><td>Comprehensive Complication Index 0-30 days</td><td>Mean (SD)</td><td>17.0 +/- 19.7</td><td>14.6 +/- 17.7</td><td>B * (95% CI)</td><td>-1.20 (-3.38; 0.97)</td><td>0.36</td></tr><tr><td></td><td>Median (IQR)</td><td>20.6 (0-24.2)</td><td>8.7 (0-24.5)</td><td></td><td></td><td></td></tr><tr><td>Late Complications</td><td>n (%)</td><td>28 (19.6)</td><td>23 (16.1)</td><td>OR ^ (95% CI)</td><td>0.79 (0.4; 1.5)</td><td>0.448</td></tr><tr><td>Clavien-Major</td><td>n (%)</td><td>12 (8.4)</td><td>12 (8.4)</td><td>OR ^ (95% CI)</td><td>1.5 (0.5; 4.4)</td><td>0.511</td></tr><tr><td>Late Readmission</td><td>n (%)</td><td>19 (13.3)</td><td>20 (14.0)</td><td>OR ^ (95% CI)</td><td>0.75 (0.4; 1.5)</td><td>0.398</td></tr><tr><td>Comprehensive Complication Index 0-90 days</td><td>Mean (SD)</td><td>20.4 (20.6)</td><td>17.4 +/- 20.8</td><td>B * (95% CI)</td><td>-1.50 (-3.91; 0.91)</td><td>0.16</td></tr><tr><td></td><td>Median (IQR)</td><td>20.6 (0-29.6)</td><td>20.6 (0-29.6)</td><td></td><td></td><td></td></tr><tr><td>Creatinine (mg/L)</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Pre-operative</td><td>Mean (SD)</td><td>1.1 (0.6)</td><td>1.0 (0.3)</td><td></td><td></td><td>0.081</td></tr><tr><td>Post-operative</td><td>Mean (SD)</td><td>1.1 (0.4)</td><td>0.9 (0.3)</td><td></td><td></td><td>0.007</td></tr><tr><td>Delta (Δ)</td><td>Mean (SD)</td><td>0.0 (0.4)</td><td>-0.0 (0.3)</td><td></td><td></td><td>0.59</td></tr><tr><td>Hemoglobin (g/dL)</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Pre-operative</td><td>Mean (SD)</td><td>13.5 (2.0)</td><td>13.4 (1.9)</td><td></td><td></td><td>0.814</td></tr><tr><td>Post-operative</td><td>Mean (SD)</td><td>10.6 (1.3)</td><td>10.9 (1.4)</td><td></td><td></td><td>0.130</td></tr><tr><td>Delta (Δ)</td><td>Mean (SD)</td><td>-2.9 (1.9)</td><td>-2.6 (1.7)</td><td></td><td></td><td>0.170</td></tr><tr><td>pT stage</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>pT0</td><td></td><td>25</td><td>17.5</td><td>15</td><td>10.5</td><td>0.351</td></tr><tr><td>pTa-pTis-pT1</td><td></td><td>69</td><td>48.3</td><td>93</td><td>65.0</td><td></td></tr><tr><td>pT2</td><td></td><td>14</td><td>9.8</td><td>14</td><td>9.8</td><td></td></tr><tr><td>pT3-4</td><td></td><td>35</td><td>24.5</td><td>21</td><td>14.7</td><td></td></tr></tbody></table>
<table><caption>**Table 2.** *Cont.*</caption><thead><tr><th></th><th>ORC (n = 143)</th><th>RARC (n = 143)</th><th>RARC vs. ORC</th><th>p</th></tr></thead><tbody><tr><td>pT stage</td><td></td><td></td><td></td><td>0.069</td></tr><tr><td>pN0</td><td>125</td><td>87.4</td><td>124</td><td>0.738</td></tr><tr><td>pN1-pN3</td><td>14</td><td>9.8</td><td>15</td><td>0.738</td></tr><tr><td>pNx</td><td>4</td><td>2.8</td><td>4</td><td>0.738</td></tr><tr><td>LN removed</td><td>Mean (SD)</td><td>21.0 (13.2)</td><td>143</td><td>21.3 (11.1)</td></tr><tr><td></td><td>Median (IQR)</td><td>17 (11; 28)</td><td></td><td>19 (13; 29)</td></tr><tr><td>Carcinoma in situ at RC</td><td>72</td><td>51.1</td><td>69</td><td>0.656</td></tr><tr><td>Positive ureteral/urethral margins</td><td>10</td><td>7.0</td><td>12</td><td>0.640</td></tr></tbody></table>

<table><caption>**Table 3.** Pathological results.</caption><thead><tr><th></th><th></th><th colspan="2">ORC (n = 143)</th><th colspan="2">RARC (n = 143)</th><th>p</th></tr><tr><th></th><th></th><th>n</th><th>%</th><th>n</th><th>%</th><th></th></tr></thead><tbody><tr><td rowspan="5">pT stage</td><td>pT0</td><td>25</td><td>17.5</td><td>15</td><td>10.5</td><td rowspan="5">0.351</td></tr><tr><td>pTa-pTis-pT1</td><td>69</td><td>48.3</td><td>93</td><td>65.0</td></tr><tr><td>pT2</td><td>14</td><td>9.8</td><td>14</td><td>9.8</td></tr><tr><td>pT3-4</td><td>35</td><td>24.5</td><td>21</td><td>14.7</td></tr><tr><td>pT2-pT4</td><td>49</td><td>34.3</td><td>35</td><td>24.5</td></tr><tr><td rowspan="4">pN stage</td><td>pN0</td><td>125</td><td>87.4</td><td>124</td><td>86.7</td><td rowspan="4">0.738</td></tr><tr><td>pN1-pN3</td><td>14</td><td>9.8</td><td>15</td><td>10.5</td></tr><tr><td>pNx</td><td>4</td><td>2.8</td><td>4</td><td>2.8</td></tr><tr><td>Mean (SD)</td><td>143</td><td>21.0 (13.2)</td><td>143</td><td>21.3 (11.1)</td></tr><tr><td></td><td>Median (IQR)</td><td></td><td>17 (11; 28)</td><td></td><td>19 (13; 29)</td><td></td></tr><tr><td>Carcinoma in situ at RC *</td><td></td><td>72</td><td>51.1</td><td>69</td><td>48.3</td><td>0.656</td></tr><tr><td>Positive ureteral/urethral margins</td><td></td><td>10</td><td>7.0</td><td>12</td><td>8.4</td><td>0.640</td></tr></tbody></table>

Mean (SD) follow-up for the cohort was 20 ± 18 months for ORC and 22 ± 18 months for RARC. A total of 49 recurrences occurred, of which 31 were in ORC and 18 were in RARC. The disease-free survival at 60 months was 55.9% in ORC and 75.2% in RARC with a statistically significant difference (HR = 0.53, 95% CI: 0.29; 0.95, *p* = 0.033) in the univariate analysis (Figure 1). In Cox multivariate regression, after adjustment for the pT stage on the radical cystectomy specimen, this difference became non-significant (HR 0.56, 95% CI: 0.31; 1.02, *p* = 0.06). Forty-six patients died during follow-up, of which thirty-four related to bladder cancer. Cancer-specific (HR 0.58, 95% CI: 0.31; 1.09, *p* = 0.09) and overall survival (HR 0.59, 95% CI: 0.33; 1.04, *p* = 0.07) were not statistically different across the two surgical approaches (Figure 1).

<footnote>* Linear regression with robust clustered (matching) errors; ^ Logistic regression with robust clustered (matching) errors; ° Poisson regression with robust clustered (matching) errors.</footnote>

<footnote>*: Radical Cystectomy.</footnote>
<table><caption>**Table 2.** *Cont.*</caption><thead><tr><th></th><th>ORC (n = 143)</th><th>RARC (n = 143)</th><th>RARC vs. ORC</th><th>p</th></tr></thead><tbody><tr><td>pT stage</td><td></td><td></td><td></td><td>0.069</td></tr><tr><td>pN0</td><td>125</td><td>87.4</td><td>124</td><td>0.738</td></tr><tr><td>pN1-pN3</td><td>14</td><td>9.8</td><td>15</td><td>0.738</td></tr><tr><td>pNx</td><td>4</td><td>2.8</td><td>4</td><td>0.738</td></tr><tr><td>LN removed</td><td>Mean (SD)</td><td>21.0 (13.2)</td><td>143</td><td>21.3 (11.1)</td></tr><tr><td></td><td>Median (IQR)</td><td>17 (11; 28)</td><td></td><td>19 (13; 29)</td></tr><tr><td>Carcinoma in situ at RC</td><td>72</td><td>51.1</td><td>69</td><td>0.656</td></tr><tr><td>Positive ureteral/urethral margins</td><td>10</td><td>7.0</td><td>12</td><td>0.640</td></tr></tbody></table>

<table><caption>**Table 3.** Pathological results.</caption><thead><tr><th rowspan="2"></th><th rowspan="2"></th><th colspan="2">ORC (n = 143)</th><th colspan="2">RARC (n = 143)</th><th rowspan="2">p</th></tr><tr><th>n</th><th>%</th><th>n</th><th>%</th></tr></thead><tbody><tr><td rowspan="5">pT stage</td><td>pT0</td><td>25</td><td>17.5</td><td>15</td><td>10.5</td><td rowspan="5">0.351</td></tr><tr><td>pTa-pTis-pT1</td><td>69</td><td>48.3</td><td>93</td><td>65.0</td></tr><tr><td>pT2</td><td>14</td><td>9.8</td><td>14</td><td>9.8</td></tr><tr><td>pT3-4</td><td>35</td><td>24.5</td><td>21</td><td>14.7</td></tr><tr><td>pT2-pT4</td><td>49</td><td>34.3</td><td>35</td><td>24.5</td></tr><tr><td rowspan="4">pN stage</td><td>pN0</td><td>125</td><td>87.4</td><td>124</td><td>86.7</td><td rowspan="4">0.738</td></tr><tr><td>pN1-pN3</td><td>14</td><td>9.8</td><td>15</td><td>10.5</td></tr><tr><td>pNx</td><td>4</td><td>2.8</td><td>4</td><td>2.8</td></tr><tr><td>Mean (SD)</td><td>143</td><td>21.0 (13.2)</td><td>143</td><td>21.3 (11.1)</td></tr><tr><td></td><td>Median (IQR)</td><td></td><td>17 (11; 28)</td><td></td><td>19 (13; 29)</td><td></td></tr><tr><td colspan="2">Carcinoma in situ at RC *</td><td>72</td><td>51.1</td><td>69</td><td>48.3</td><td>0.656</td></tr><tr><td colspan="2">Positive ureteral/urethral margins</td><td>10</td><td>7.0</td><td>12</td><td>8.4</td><td>0.640</td></tr></tbody></table>

Mean (SD) follow-up for the cohort was 20 ± 18 months for ORC and 22 ± 18 months for RARC. A total of 49 recurrences occurred, of which 31 were in ORC and 18 were in RARC. The disease-free survival at 60 months was 55.9% in ORC and 75.2% in RARC with a statistically significant difference (HR = 0.53, 95% CI: 0.29; 0.95, *p* = 0.033) in the univariate analysis (Figure 1). In Cox multivariate regression, after adjustment for the pT stage on the radical cystectomy specimen, this difference became non-significant (HR 0.56, 95% CI: 0.31; 1.02, *p* = 0.06). Forty-six patients died during follow-up, of which thirty-four related to bladder cancer. Cancer-specific (HR 0.58, 95% CI: 0.31; 1.09, *p* = 0.09) and overall survival (HR 0.59, 95% CI: 0.33; 1.04, *p* = 0.07) were not statistically different across the two surgical approaches (Figure 1).

<footnote>* Linear regression with robust clustered (matching) errors; ^ Logistic regression with robust clustered (matching) errors; ° Poisson regression with robust clustered (matching) errors.</footnote>

<footnote>*: Radical Cystectomy.</footnote>
<figure><img src="image_4.png" /><figcaption>**Figure 1.** Kaplan–Meier curves for disease-free survival, cancer-specific survival and overall survival according to surgical approach.</figcaption></figure>

**4. Discussion**

NMIBC is a potentially lethal disease with a major impact on patients’ lives and health-care costs [14,15]. Choosing adequate treatment for patients can be challenging [16]. To our knowledge, this is the first comparative study on perioperative and oncologic outcomes of iRARC vs. ORC in patients with NIMBC. We reported that iRARC was associated with reduced blood loss and transfusions and reduced length of hospital stay without increased readmission rates. Nonetheless, we did not find any significant differences in post-operative morbidity, in terms of the Clavien–Dindo classification or the comprehensive complication index across the two surgical techniques. Concerning oncologic outcomes, although the DFS appeared higher in the iRARC group in univariate analysis, this is due to the increased, though not significant, >pT2 rate in the final pathology found in the ORC group.

In this study, we compared surgical outcomes across two different approaches including patients from several centers, where RC is usually carried out either by an open or a robotic approach, in an attempt to reduce selection bias. Moreover, we performed a
<figure><img src="image_4.png" /><figcaption>**Figure 1.** Kaplan–Meier curves for disease-free survival, cancer-specific survival and overall survival according to surgical approach.</figcaption></figure>

**4. Discussion**

NMIBC is a potentially lethal disease with a major impact on patients’ lives and health-care costs [14,15]. Choosing adequate treatment for patients can be challenging [16]. To our knowledge, this is the first comparative study on perioperative and oncologic outcomes of iRARC vs. ORC in patients with NIMBC. We reported that iRARC was associated with reduced blood loss and transfusions and reduced length of hospital stay without increased readmission rates. Nonetheless, we did not find any significant differences in post-operative morbidity, in terms of the Clavien–Dindo classification or the comprehensive complication index across the two surgical techniques. Concerning oncologic outcomes, although the DFS appeared higher in the iRARC group in univariate analysis, this is due to the increased, though not significant, >pT2 rate in the final pathology found in the ORC group.

In this study, we compared surgical outcomes across two different approaches including patients from several centers, where RC is usually carried out either by an open or a robotic approach, in an attempt to reduce selection bias. Moreover, we performed a
propensity score match-pair analysis to achieve greater statistical reliability. We confirmed findings of the trials for MIBC [6,17], reporting a longer operative time (20 min) in the iRARC group, although we believe this difference is not clinically relevant. On the other hand, hospital stay was shorter (3 days) in the RARC group; although such difference appears greater than previously reported, our average LOS was longer than that of other US-based RCTs [6,7]. This must be attributed to inherent and socio-cultural differences in European and US healthcare systems.

The rate of complications was similar between the two groups, ranging from 51.8 to 59.4%. This rate is similar to those reported in MIBC-patients, for both surgical approaches as reported by Shabsigh et al. [3]. In several randomized trials [6,7], no major advantage to robotic surgery was observed regarding complication rates. Bochner et al. found no difference between the two surgical approaches (62% and 66% of RARC and ORC patients, respectively). In the RAZOR trial, there was no difference in 90 d complication, with an overall complication rate of 67% vs. 69%, respectively. In a meta-analysis by Clement et al. (including 12,640 patients comparing RARC to ORC), major complications rates were lower in the RARC group than in the ORC group [18]. On the other hand, a second meta-analysis, by Rai et al. that only included randomized trials, did not confirm these differences [19]. In the present study, we reported the comprehensive complication index for ORC and iRARC in patients with NMIBC. To our knowledge, this is the first study to explore complications for this subset of patients using the novel comprehensive index. However, no statistically significant difference was found.

The difference in DFS across the two groups deserves some reflection. Logically, the
difference in pT stage (with a higher rate in >pT2 in the ORC arm, although not statistically
significant) resulted in a lower recurrence-free survival rate in ORC [20]. On the other
hand, the reduced transfusion rate in the RARC arm could positively affect the oncologic
follow-up of patients and be associated with an improved DFS [21]. The extent of lymph
node dissection can also influence oncologic outcomes: Khanna et al. published a large
retrospective cohort of 1647 patients with NMIBC undergoing RC [9]. They reported a
median LN count of 15 nodes, which was lower than the one reported in the present study.
In multivariable analysis, a LN count >20 was associated with improved CSS (HR 0.67, 95%
CI: 0.52; 0.87, *p* = 0.002) and OS (HR 0.75, 95% CI: 0.64; 0.88, *p* < 0.001). Nonetheless, in
our study, the number of resected nodes (mean 21 vs. 21.3, *p* = 0.485) was not significantly
different across the RARC and ORC cohorts, thus not justifying the observed difference
in DFS in the univariate analysis in the present study. Another potential difference across
our two matched cohorts could be the rate re-TUR, for which we are lacking data. Re-TUR
has a major impact in proper patient selection before surgery [22,23]; we are unable to
define whether an increased implementation of re-TUR in the iRARC arm of the present
study could explain the rates of upstaging to ≥pT2 disease observed in the two arms. In a
large series of cystectomies for NMIBC, Soria et al. [20] found that 50% of patients were
upstaged after RC. Female gender and older age were associated with upstaging in this
series; nonetheless, both factors were matched parameters in the present study and were
comparable in the two groups. Iqbal et al. [24] described a large series of patients who
underwent RARC for NMIBC with an upstaging rate of 31%, associated with older age,
cT1 vs. cTa or Tis, and pre-operative hydronephrosis.

Our study is not devoid of limitations: First, a mean follow-up of roughly two years
can be considered insufficient, especially for hard outcomes such as CSS and OS. Second,
although all centers record data in a prospective manner; the retrospective design of
the matched-pair analysis may increase bias. Third, quality of life and patient reported
outcome measures were not available to be analyzed across the two surgical techniques.
Fourth, in the present study, 47% of patients had upfront radical cystectomy, without prior
intravesical therapy, and this may not reflect current practice. This elevated rate may be
explained by the BCG shortage which marked the years 2015–2020 during which patients
were included. Moreover, a selection bias for patients with more aggressive disease is likely:
we are unable to determine the rate of variant histologies, lymphovascular invasion or
propensity score match-pair analysis to achieve greater statistical reliability. We confirmed findings of the trials for MIBC [6,17], reporting a longer operative time (20 min) in the iRARC group, although we believe this difference is not clinically relevant. On the other hand, hospital stay was shorter (3 days) in the RARC group; although such difference appears greater than previously reported, our average LOS was longer than that of other US-based RCTs [6,7]. This must be attributed to inherent and socio-cultural differences in European and US healthcare systems.

The rate of complications was similar between the two groups, ranging from 51.8 to 59.4%. This rate is similar to those reported in MIBC-patients, for both surgical approaches as reported by Shabsigh et al. [3]. In several randomized trials [6,7], no major advantage to robotic surgery was observed regarding complication rates. Bochner et al. found no difference between the two surgical approaches (62% and 66% of RARC and ORC patients, respectively). In the RAZOR trial, there was no difference in 90 d complication, with an overall complication rate of 67% vs. 69%, respectively. In a meta-analysis by Clement et al. (including 12,640 patients comparing RARC to ORC), major complications rates were lower in the RARC group than in the ORC group [18]. On the other hand, a second meta-analysis, by Rai et al. that only included randomized trials, did not confirm these differences [19]. In the present study, we reported the comprehensive complication index for ORC and iRARC in patients with NMIBC. To our knowledge, this is the first study to explore complications for this subset of patients using the novel comprehensive index. However, no statistically significant difference was found.

The difference in DFS across the two groups deserves some reflection. Logically, the
difference in pT stage (with a higher rate in >pT2 in the ORC arm, although not statistically
significant) resulted in a lower recurrence-free survival rate in ORC [20]. On the other
hand, the reduced transfusion rate in the RARC arm could positively affect the oncologic
follow-up of patients and be associated with an improved DFS [21]. The extent of lymph
node dissection can also influence oncologic outcomes: Khanna et al. published a large
retrospective cohort of 1647 patients with NMIBC undergoing RC [9]. They reported a
median LN count of 15 nodes, which was lower than the one reported in the present study.
In multivariable analysis, a LN count >20 was associated with improved CSS (HR 0.67, 95%
CI: 0.52; 0.87, *p* = 0.002) and OS (HR 0.75, 95% CI: 0.64; 0.88, *p* < 0.001). Nonetheless, in
our study, the number of resected nodes (mean 21 vs. 21.3, *p* = 0.485) was not significantly
different across the RARC and ORC cohorts, thus not justifying the observed difference
in DFS in the univariate analysis in the present study. Another potential difference across
our two matched cohorts could be the rate re-TUR, for which we are lacking data. Re-TUR
has a major impact in proper patient selection before surgery [22,23]; we are unable to
define whether an increased implementation of re-TUR in the iRARC arm of the present
study could explain the rates of upstaging to ≥pT2 disease observed in the two arms. In a
large series of cystectomies for NMIBC, Soria et al. [20] found that 50% of patients were
upstaged after RC. Female gender and older age were associated with upstaging in this
series; nonetheless, both factors were matched parameters in the present study and were
comparable in the two groups. Iqbal et al. [24] described a large series of patients who
underwent RARC for NMIBC with an upstaging rate of 31%, associated with older age,
cT1 vs. cTa or Tis, and pre-operative hydronephrosis.

Our study is not devoid of limitations: First, a mean follow-up of roughly two years
can be considered insufficient, especially for hard outcomes such as CSS and OS. Second,
although all centers record data in a prospective manner; the retrospective design of
the matched-pair analysis may increase bias. Third, quality of life and patient reported
outcome measures were not available to be analyzed across the two surgical techniques.
Fourth, in the present study, 47% of patients had upfront radical cystectomy, without prior
intravesical therapy, and this may not reflect current practice. This elevated rate may be
explained by the BCG shortage which marked the years 2015–2020 during which patients
were included. Moreover, a selection bias for patients with more aggressive disease is likely:
we are unable to determine the rate of variant histologies, lymphovascular invasion or
other factors determining very high-risk NMIBC, which could have driven the decision for radical surgery. Finally, the absence of a standardized post-operative pathway may have contributed to the variability of post-operative morbidity. On the other hand, this is, to the best our knowledge, the largest study to date comparing iRARC to ORC for patients with NMIBC while using propensity matched-pair analysis to allow the most adequate comparison across the two surgical techniques.

**5. Conclusions**

In this propensity score matched-pair analysis, iRARC for patients with NMIBC is associated with reduced blood loss, reduced transfusions and reduced hospital stay compared to the open counterpart. However, we did not observe significant differences in surgical morbidity. The two approaches appear comparable in terms of oncologic outcomes. Prospective randomized trials are needed to validate the present findings.

**Author Contributions:** E.C. and S.A. gave substantial contributions to the conception and the design of the manuscript. All authors participated in data gathering. V.P. was responsible for statistical analysis. All authors participated in drafting the manuscript. R.M., T.R. and S.A. revised it critically. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of Comité Nacional Informatique et Liberté (code 2227169).

**Informed Consent Statement:** Informed oral consent was given for all subjects involved in the study.

**Data Availability Statement:** Research data are available if needed.

**Conflicts of Interest:** Thierry Quackels: healthcare professional services agreement with Intuitive Surgical. Gregory Verhoest: healthcare professional services agreement with Intuitive Surgical. Others authors have nothing to disclose.

**References**

1. Cumberbatch, M.G.K.; Jubber, I.; Black, P.C.; Esperto, F.; Figueroa, J.D.; Kamat, A.M.; Kiemeney, L.; Lotan, Y.; Pang, K.; Silverman, D.T.; et al. Epidemiology of Bladder Cancer: A Systematic Review and Contemporary Update of Risk Factors in 2018. *Eur. Urol.* **2018**, *74*, 784–795. [CrossRef]

2. Babjuk, M.; Burger, M.; Capoun, O.; Cohen, D.; Compérat, E.M.; Escrig, J.L.D.; Gontero, P.; Liedberg, F.; Masson-Lecomte, A.; Mostafid, A.H.; et al. European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ). *Eur. Urol.* **2021**, *81*, 75–94. [CrossRef] [PubMed]

3. Shabsigh, A.; Korets, R.; Vora, K.C.; Brooks, C.M.; Cronin, A.M.; Savage, C.; Raj, G.; Bochner, B.H.; Dalbagni, G.; Herr, H.W.; et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. *Eur. Urol.* **2009**, *55*, 164–176. [CrossRef] [PubMed]

4. Zhou, N.; Tian, F.; Feng, Y.; Zhao, K.; Chen, L.; Fan, R.; Lu, W.; Gu, C. Perioperative outcomes of intracorporeal robot-assisted radical cystectomy versus open radical cystectomy: A systematic review and meta-analysis of comparative studies. *Int. J. Surg.* **2021**, *94*, 106137. [CrossRef] [PubMed]

5. Liu, H.; Zhou, Z.; Yao, H.; Mao, Q.; Chu, Y.; Cui, Y.; Wu, J. Robot-assisted radical cystectomy vs open radical cystectomy in patients with bladder cancer: A systematic review and meta-analysis of randomized controlled trials. *World J. Surg. Oncol.* **2023**, *21*, 240. [CrossRef]

6. Parekh, D.J.; Reis, I.M.; Castle, E.P.; Gonzalgo, M.L.; Woods, M.E.; Svatek, R.S.; Weizer, A.Z.; Konety, B.R.; Tollefson, M.; Krupski, T.L.; et al. Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): An open-label, randomised, phase 3, non-inferiority trial. *Lancet* **2018**, *391*, 2525–2536. [CrossRef]

7. Bochner, B.H.; Dalbagni, G.; Sjoberg, D.D.; Silberstein, J.; Keren Paz, G.E.; Donat, S.M.; Coleman, J.A.; Mathew, S.; Vickers, A.; Schnorr, G.C.; et al. Comparing Open Radical Cystectomy and Robot-assisted Laparoscopic Radical Cystectomy: A Randomized Clinical Trial. *Eur. Urol.* **2015**, *67*, 1042–1050. [CrossRef]

8. Zennami, K.; Sumitomo, M.; Takahara, K.; Nukaya, T.; Takenaka, M.; Fukaya, K.; Ichino, M.; Fukami, N.; Sasaki, H.; Kusaka, M.; et al. Intra-corporeal robot-assisted versus open radical cystectomy: A propensity score-matched analysis comparing perioperative and long-term survival outcomes and recurrence patterns. *Int. J. Clin. Oncol.* **2021**, *26*, 1514–1523. [CrossRef] [PubMed]
other factors determining very high-risk NMIBC, which could have driven the decision for radical surgery. Finally, the absence of a standardized post-operative pathway may have contributed to the variability of post-operative morbidity. On the other hand, this is, to the best our knowledge, the largest study to date comparing iRARC to ORC for patients with NMIBC while using propensity matched-pair analysis to allow the most adequate comparison across the two surgical techniques.

**5. Conclusions**

In this propensity score matched-pair analysis, iRARC for patients with NMIBC is associated with reduced blood loss, reduced transfusions and reduced hospital stay compared to the open counterpart. However, we did not observe significant differences in surgical morbidity. The two approaches appear comparable in terms of oncologic outcomes. Prospective randomized trials are needed to validate the present findings.

**Author Contributions:** E.C. and S.A. gave substantial contributions to the conception and the design of the manuscript. All authors participated in data gathering. V.P. was responsible for statistical analysis. All authors participated in drafting the manuscript. R.M., T.R. and S.A. revised it critically. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of Comité Nacional Informatique et Liberté (code 2227169).

**Informed Consent Statement:** Informed oral consent was given for all subjects involved in the study.

**Data Availability Statement:** Research data are available if needed.

**Conflicts of Interest:** Thierry Quackels: healthcare professional services agreement with Intuitive Surgical. Gregory Verhoest: healthcare professional services agreement with Intuitive Surgical. Others authors have nothing to disclose.

**References**

1. Cumberbatch, M.G.K.; Jubber, I.; Black, P.C.; Esperto, F.; Figueroa, J.D.; Kamat, A.M.; Kiemeney, L.; Lotan, Y.; Pang, K.; Silverman, D.T.; et al. Epidemiology of Bladder Cancer: A Systematic Review and Contemporary Update of Risk Factors in 2018. *Eur. Urol.* **2018**, *74*, 784–795. [CrossRef]

2. Babjuk, M.; Burger, M.; Capoun, O.; Cohen, D.; Compérat, E.M.; Escrig, J.L.D.; Gontero, P.; Liedberg, F.; Masson-Lecomte, A.; Mostafid, A.H.; et al. European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ). *Eur. Urol.* **2021**, *81*, 75–94. [CrossRef] [PubMed]

3. Shabsigh, A.; Korets, R.; Vora, K.C.; Brooks, C.M.; Cronin, A.M.; Savage, C.; Raj, G.; Bochner, B.H.; Dalbagni, G.; Herr, H.W.; et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. *Eur. Urol.* **2009**, *55*, 164–176. [CrossRef] [PubMed]

4. Zhou, N.; Tian, F.; Feng, Y.; Zhao, K.; Chen, L.; Fan, R.; Lu, W.; Gu, C. Perioperative outcomes of intracorporeal robot-assisted radical cystectomy versus open radical cystectomy: A systematic review and meta-analysis of comparative studies. *Int. J. Surg.* **2021**, *94*, 106137. [CrossRef] [PubMed]

5. Liu, H.; Zhou, Z.; Yao, H.; Mao, Q.; Chu, Y.; Cui, Y.; Wu, J. Robot-assisted radical cystectomy vs open radical cystectomy in patients with bladder cancer: A systematic review and meta-analysis of randomized controlled trials. *World J. Surg. Oncol.* **2023**, *21*, 240. [CrossRef]

6. Parekh, D.J.; Reis, I.M.; Castle, E.P.; Gonzalgo, M.L.; Woods, M.E.; Svatek, R.S.; Weizer, A.Z.; Konety, B.R.; Tollefson, M.; Krupski, T.L.; et al. Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): An open-label, randomised, phase 3, non-inferiority trial. *Lancet* **2018**, *391*, 2525–2536. [CrossRef]

7. Bochner, B.H.; Dalbagni, G.; Sjoberg, D.D.; Silberstein, J.; Keren Paz, G.E.; Donat, S.M.; Coleman, J.A.; Mathew, S.; Vickers, A.; Schnorr, G.C.; et al. Comparing Open Radical Cystectomy and Robot-assisted Laparoscopic Radical Cystectomy: A Randomized Clinical Trial. *Eur. Urol.* **2015**, *67*, 1042–1050. [CrossRef]

8. Zennami, K.; Sumitomo, M.; Takahara, K.; Nukaya, T.; Takenaka, M.; Fukaya, K.; Ichino, M.; Fukami, N.; Sasaki, H.; Kusaka, M.; et al. Intra-corporeal robot-assisted versus open radical cystectomy: A propensity score-matched analysis comparing perioperative and long-term survival outcomes and recurrence patterns. *Int. J. Clin. Oncol.* **2021**, *26*, 1514–1523. [CrossRef] [PubMed]
9. Khanna, A.; Miest, T.; Sharma, V.; Campbell, R.; Hensley, P.; Thapa, P.; Zganjar, A.; Tollefson, M.K.; Thompson, R.H.; Frank, I.; et al. Role of lymphadenectomy during radical cystectomy for nonmuscle-invasive bladder cancer: Results from a multi-institutional experience. *J. Urol.* **2022**, *207*, 551–558. [CrossRef]

10. Kayama, E.; Kikuchi, E.; Fukumoto, K.; Shirotake, S.; Miyazaki, Y.; Hakozaki, K.; Kaneko, G.; Yoshimine, S.; Tanaka, N.; Takahiro, M.; et al. History of Non-Muscle-Invasive Bladder Cancer May Have a Worse Prognostic Impact in cT2-4aN0M0 Bladder Cancer Patients Treated With Radical Cystectomy. *Clin. Genitourin. Cancer* **2018**, *16*, e969–e976. [CrossRef]

11. Albisinni, S.; Moschini, M.; Di Trapani, E.; Soria, F.; Mari, A.; Aziz, A.; Teoh, J.; Laukhtina, E.; Mori, K.; D'andrea, D.; et al. Current application of the enhanced recovery after surgery protocol for patients undergoing radical cystectomy: Lessons learned from European excellence centers. *World J. Urol.* **2021**, *40*, 1317–1323. [CrossRef] [PubMed]

12. Mitropoulos, D.; Artibani, W.; Biyani, C.S.; Jensen, J.B.; Rouprêt, M.; Truss, M. Validation of the clavien-dindo grading system in urology by the european association of urology guidelines ad hoc panel. *Eur. Urol. Focus* **2018**, *4*, 608–613. [CrossRef] [PubMed]

13. Vetterlein, M.W.; Klemm, J.; Gild, P.; Bradtke, M.; Soave, A.; Dahlem, R.; Fisch, M.; Rink, M. Improving estimates of perioperative morbidity after radical cystectomy using the European Association of urology quality criteria for standardized reporting and introducing the comprehensive complication index. *Eur. Urol.* **2019**, *77*, 55–65. [CrossRef] [PubMed]

14. Jung, A.; Nielsen, M.E.; Crandell, J.L.; Palmer, M.H.; Smith, S.K.; Bryant, A.L.; Mayer, D.K. Health-related quality of life among non-muscle-invasive bladder cancer survivors: A population-based study. *BJU Int.* **2019**, *125*, 38–48. [CrossRef]

15. Nishimura, N.; Miyake, M.; Nakahama, T.; Miyamoto, T.; Nishimoto, K.; Oyama, M.; Matsushita, Y.; Miyake, H.; Fukuhara, H.; Inoue, K.; et al. Impact on Japanese healthcare economics of photodynamic diagnosis-assisted transurethral resection of bladder tumor for non-muscle invasive bladder cancer: A multicenter retrospective cohort study. *Int J Urol.* **2023**. [CrossRef] [PubMed]

16. Catto, J.W.F.; Gordon, K.; Collinson, M.; Poad, H.; Twiddy, M.; Johnson, M.; Jain, S.; Chahal, R.; Simms, M.; Dooldeniya, M.; et al. Radical cystectomy against intravesical BCG for high-risk high-grade nonmuscle invasive bladder cancer: Results from the randomized controlled BRAVO-feasibility study. *J. Clin. Oncol.* **2021**, *39*, 202–214. [CrossRef]

17. Parekh, D.J.; Messer, J.; Fitzgerald, J.; Ercole, B.; Svatek, R. Perioperative outcomes and oncologic efficacy from a pilot prospective randomized clinical trial of open versus robotic assisted radical cystectomy. *J. Urol.* **2013**, *189*, 474–479. [CrossRef]

18. Clement, K.D.; Pearce, E.; Gabr, A.H.; Rai, B.P.; Al-Ansari, A.; Aboumarzouk, O.M. Perioperative outcomes and safety of robotic vs open cystectomy: A systematic review and meta-analysis of 12,640 cases. *World J. Urol.* **2020**, *39*, 1733–1746. [CrossRef]

19. Rai, B.P.; Bondad, J.; Vasdev, N.; Adshead, J.; Lane, T.; Ahmed, K.; Khan, M.S.; Dasgupta, P.; Guru, K.; Chlosta, P.L.; et al. Robotic versus open radical cystectomy for bladder cancer in adults. *Cochrane Database Syst. Rev.* **2019**, *2019*, CD011903. [CrossRef]

20. Soria, F.; Pisano, F.; Gontero, P.; Palou, J.; Joniau, S.; Serretta, V.; Larré, S.; Di Stasi, S.; van Rhijn, B.; Witjes, J.A.; et al. Predictors of oncological outcomes in T1G3 patients treated with BCG who undergo radical cystectomy. *World J. Urol.* **2018**, *36*, 1775–1781. [CrossRef]

21. Furrer, M.A.; Fellmann, A.; Schneider, M.P.; Thalmann, G.N.; Burkhard, F.C.; Wuethrich, P.Y. Impact of packed red blood cells and fresh frozen plasma given during radical cystectomy and urinary diversion on cancer-related outcome and survival: An observational cohort study. *Eur. Urol. Focus* **2018**, *4*, 916–923. [CrossRef] [PubMed]

22. Audenet, F.; Retinger, C.; Chien, C.; Benfante, N.E.; Bochner, B.H.; Donat, S.M.; Herr, H.W.; Dalbagni, G. Is restaging transurethral resection necessary in patients with non-muscle invasive bladder cancer and limited lamina propria invasion. In *Urologic Oncology: Seminars and Original Investigations*; Elsevier: Amsterdam, The Netherlands, 2017; p. 603-e1.

23. Sfakianos, J.P.; Kim, P.H.; Hakimi, A.A.; Herr, H.W. The effect of restaging transurethral resection on recurrence and progression rates in patients with nonmuscle invasive bladder cancer treated with intravesical bacillus calmette-guérin. *J. Urol.* **2014**, *191*, 341–345. [CrossRef] [PubMed]

24. Iqbal, U.; Elsayed, A.S.; Jing, Z.; Stoeckle, M.; Wijburg, C.; Wiklund, P.; Hosseini, A.; Dasgupta, P.; Khan, M.S.; Hemal, A.; et al. Upstaging and Survival Outcomes for Non-Muscle Invasive Bladder Cancer After Radical Cystectomy: Results from the International Robotic Cystectomy Consortium. *J. Endourol.* **2021**, *35*, 1541–1547. [CrossRef] [PubMed]

**Disclaimer/Publisher's Note:** The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.
9. Khanna, A.; Miest, T.; Sharma, V.; Campbell, R.; Hensley, P.; Thapa, P.; Zganjar, A.; Tollefson, M.K.; Thompson, R.H.; Frank, I.; et al. Role of lymphadenectomy during radical cystectomy for nonmuscle-invasive bladder cancer: Results from a multi-institutional experience. *J. Urol.* **2022**, *207*, 551–558. [CrossRef]

10. Kayama, E.; Kikuchi, E.; Fukumoto, K.; Shirotake, S.; Miyazaki, Y.; Hakozaki, K.; Kaneko, G.; Yoshimine, S.; Tanaka, N.; Takahiro, M.; et al. History of Non-Muscle-Invasive Bladder Cancer May Have a Worse Prognostic Impact in cT2-4aN0M0 Bladder Cancer Patients Treated With Radical Cystectomy. *Clin. Genitourin. Cancer* **2018**, *16*, e969–e976. [CrossRef]

11. Albisinni, S.; Moschini, M.; Di Trapani, E.; Soria, F.; Mari, A.; Aziz, A.; Teoh, J.; Laukhtina, E.; Mori, K.; D'andrea, D.; et al. Current application of the enhanced recovery after surgery protocol for patients undergoing radical cystectomy: Lessons learned from European excellence centers. *World J. Urol.* **2021**, *40*, 1317–1323. [CrossRef] [PubMed]

12. Mitropoulos, D.; Artibani, W.; Biyani, C.S.; Jensen, J.B.; Rouprêt, M.; Truss, M. Validation of the clavien-dindo grading system in urology by the european association of urology guidelines ad hoc panel. *Eur. Urol. Focus* **2018**, *4*, 608–613. [CrossRef] [PubMed]

13. Vetterlein, M.W.; Klemm, J.; Gild, P.; Bradtke, M.; Soave, A.; Dahlem, R.; Fisch, M.; Rink, M. Improving estimates of perioperative morbidity after radical cystectomy using the European Association of urology quality criteria for standardized reporting and introducing the comprehensive complication index. *Eur. Urol.* **2019**, *77*, 55–65. [CrossRef] [PubMed]

14. Jung, A.; Nielsen, M.E.; Crandell, J.L.; Palmer, M.H.; Smith, S.K.; Bryant, A.L.; Mayer, D.K. Health-related quality of life among non-muscle-invasive bladder cancer survivors: A population-based study. *BJU Int.* **2019**, *125*, 38–48. [CrossRef]

15. Nishimura, N.; Miyake, M.; Nakahama, T.; Miyamoto, T.; Nishimoto, K.; Oyama, M.; Matsushita, Y.; Miyake, H.; Fukuhara, H.; Inoue, K.; et al. Impact on Japanese healthcare economics of photodynamic diagnosis-assisted transurethral resection of bladder tumor for non-muscle invasive bladder cancer: A multicenter retrospective cohort study. *Int J Urol.* **2023**. [CrossRef] [PubMed]

16. Catto, J.W.F.; Gordon, K.; Collinson, M.; Poad, H.; Twiddy, M.; Johnson, M.; Jain, S.; Chahal, R.; Simms, M.; Dooldeniya, M.; et al. Radical cystectomy against intravesical BCG for high-risk high-grade nonmuscle invasive bladder cancer: Results from the randomized controlled BRAVO-feasibility study. *J. Clin. Oncol.* **2021**, *39*, 202–214. [CrossRef]

17. Parekh, D.J.; Messer, J.; Fitzgerald, J.; Ercole, B.; Svatek, R. Perioperative outcomes and oncologic efficacy from a pilot prospective randomized clinical trial of open versus robotic assisted radical cystectomy. *J. Urol.* **2013**, *189*, 474–479. [CrossRef]

18. Clement, K.D.; Pearce, E.; Gabr, A.H.; Rai, B.P.; Al-Ansari, A.; Aboumarzouk, O.M. Perioperative outcomes and safety of robotic vs open cystectomy: A systematic review and meta-analysis of 12,640 cases. *World J. Urol.* **2020**, *39*, 1733–1746. [CrossRef]

19. Rai, B.P.; Bondad, J.; Vasdev, N.; Adshead, J.; Lane, T.; Ahmed, K.; Khan, M.S.; Dasgupta, P.; Guru, K.; Chlosta, P.L.; et al. Robotic versus open radical cystectomy for bladder cancer in adults. *Cochrane Database Syst. Rev.* **2019**, *2019*, CD011903. [CrossRef]

20. Soria, F.; Pisano, F.; Gontero, P.; Palou, J.; Joniau, S.; Serretta, V.; Larré, S.; Di Stasi, S.; van Rhijn, B.; Witjes, J.A.; et al. Predictors of oncological outcomes in T1G3 patients treated with BCG who undergo radical cystectomy. *World J. Urol.* **2018**, *36*, 1775–1781. [CrossRef]

21. Furrer, M.A.; Fellmann, A.; Schneider, M.P.; Thalmann, G.N.; Burkhard, F.C.; Wuethrich, P.Y. Impact of packed red blood cells and fresh frozen plasma given during radical cystectomy and urinary diversion on cancer-related outcome and survival: An observational cohort study. *Eur. Urol. Focus* **2018**, *4*, 916–923. [CrossRef] [PubMed]

22. Audenet, F.; Retinger, C.; Chien, C.; Benfante, N.E.; Bochner, B.H.; Donat, S.M.; Herr, H.W.; Dalbagni, G. Is restaging transurethral resection necessary in patients with non-muscle invasive bladder cancer and limited lamina propria invasion. In *Urologic Oncology: Seminars and Original Investigations*; Elsevier: Amsterdam, The Netherlands, 2017; p. 603-e1.

23. Sfakianos, J.P.; Kim, P.H.; Hakimi, A.A.; Herr, H.W. The effect of restaging transurethral resection on recurrence and progression rates in patients with nonmuscle invasive bladder cancer treated with intravesical bacillus calmette-guérin. *J. Urol.* **2014**, *191*, 341–345. [CrossRef] [PubMed]

24. Iqbal, U.; Elsayed, A.S.; Jing, Z.; Stoeckle, M.; Wijburg, C.; Wiklund, P.; Hosseini, A.; Dasgupta, P.; Khan, M.S.; Hemal, A.; et al. Upstaging and Survival Outcomes for Non-Muscle Invasive Bladder Cancer After Radical Cystectomy: Results from the International Robotic Cystectomy Consortium. *J. Endourol.* **2021**, *35*, 1541–1547. [CrossRef] [PubMed]

**Disclaimer/Publisher's Note:** The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.