Open Radical Cystectomy versus Robot-Assisted Radical Cystectomy with Intracorporeal Urinary Diversion: Early Outcomes of a Single-Center Randomized Controlled Trial
2022; Lippincott Williams & Wilkins; Volume: 207; Issue: 5 Linguagem: Inglês
10.1097/ju.0000000000002422
ISSN1527-3792
AutoresRiccardo Mastroianni, Mariaconsiglia Ferriero, Gabriele Tuderti, Umberto Anceschi, Alfredo Maria Bove, Aldo Brassetti, Leonardo Misuraca, Ashanti Zampa, Giulia Torregiani, Edoardo Ghiani, Diana Giannarelli, Salvatore Guaglianone, Michele Gallucci, Giuseppe Simone,
Tópico(s)Urinary and Genital Oncology Studies
ResumoOpen AccessJournal of UrologyAdult Urology1 May 2022Open Radical Cystectomy versus Robot-Assisted Radical Cystectomy with Intracorporeal Urinary Diversion: Early Outcomes of a Single-Center Randomized Controlled TrialThis article is commented on by the following:Editorial Comment Riccardo Mastroianni, Mariaconsiglia Ferriero, Gabriele Tuderti, Umberto Anceschi, Alfredo Maria Bove, Aldo Brassetti, Leonardo Misuraca, Ashanti Zampa, Giulia Torregiani, Edoardo Ghiani, Diana Giannarelli, Salvatore Guaglianone, Michele Gallucci, and Giuseppe Simone Riccardo MastroianniRiccardo Mastroianni *Correspondence: IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00154, Rome (RM), Italy telephone: 0652665005—+393404016868; FAX: 0652666823; email: E-mail Address: [email protected] https://orcid.org/0000-0003-3708-2209 IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy , Mariaconsiglia FerrieroMariaconsiglia Ferriero IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy , Gabriele TudertiGabriele Tuderti IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy , Umberto AnceschiUmberto Anceschi IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy , Alfredo Maria BoveAlfredo Maria Bove IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy , Aldo BrassettiAldo Brassetti IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy , Leonardo MisuracaLeonardo Misuraca IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy , Ashanti ZampaAshanti Zampa IRCCS “Regina Elena” National Cancer Institute, Department of Clinical Trial Centre, Biostatistics and Bioinformatics, Rome, Italy , Giulia TorregianiGiulia Torregiani IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy , Edoardo GhianiEdoardo Ghiani IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy , Diana GiannarelliDiana Giannarelli IRCCS “Regina Elena” National Cancer Institute, Department of Clinical Trial Centre, Biostatistics and Bioinformatics, Rome, Italy , Salvatore GuaglianoneSalvatore Guaglianone IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy , Michele GallucciMichele Gallucci IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy , and Giuseppe SimoneGiuseppe Simone IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy View All Author Informationhttps://doi.org/10.1097/JU.0000000000002422AboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Abstract Purpose: Radical cystectomy (RC) with urinary diversion (UD) is still considered a complex surgery associated with significant morbidity. Open RC (ORC) remains the reference option of treatment, even if adoption of robot-assisted RC (RARC) is rapidly increasing. To date, all the available randomized controlled trials were characterized by an extracorporeal approach in performing UD, undermining potential benefits of a totally minimally invasive procedure. In this study, we aimed to report perioperative and 6-month outcomes from the first RCT comparing ORC and RARC with totally intracorporeal UD. Materials and Methods: Patients were eligible for randomization if they had a diagnostic transurethral resection of bladder tumor with cT2-4, cN0, cM0 or recurrent high-grade nonmuscle-invasive bladder cancer and no anesthesiological contraindications to robotic surgery. Patients were enrolled with a covariate adaptive randomization process based on the following variables: body mass index, American Society of Anesthesiologists® score, baseline hemoglobin, planned UD, neoadjuvant chemotherapy and cT stage. The primary end point was to demonstrate the superiority of RARC with intracorporeal UD in terms of a 50% transfusion rate reduction. Results: Overall, 116 consecutive patients (58 RARC, 58 ORC) were enrolled. Among primary endpoint, overall perioperative transfusion rates were significantly lower in the RARC cohort (RARC: 22% vs ORC: 41%; p=0.046). Conclusions: This prospective randomized trial observed 22% and 41% overall perioperative transfusion rates in patients treated by RARC and ORC, respectively, confirming a significant benefit in favor of RARC with intracorporeal UD. However, perioperative complications, hospital stay and 6-month health-related quality of life were largely comparable between groups. Oncologic and functional outcomes will be assessed at longer followup to observe potential differences between arms. Abbreviations and Acronyms EBL estimated blood loss EORTC European Organisation for Research and Treatment of Cancer GLMER generalized linear mixed effect regression Hb baseline hemoglobin HRQoL health-related quality of life HS hospital stay ICU intensive care unit i-UD intracorporeal urinary diversion ORC open radical cystectomy OT operative time QoL quality of life RARC robot-assisted radical cystectomy RC radical cystectomy UD urinary diversion Since its discovery era, the growth of robotic surgery has been exponential. Urologists have always shown a relevant interest in minimally invasive surgery, from the initial spread of laparoscopy to the current explosion of robotic surgery, especially in the management of genitourinary cancers over the past 10 years.1 Particularly, the robotic approach has gained popularity manly because of the potential expected advantages of a minimally invasive approach, especially in terms of morbidity and quality of life (QoL). Due to the intrinsic complexity of performing a totally intracorporeal urinary diversion (i-UD), longer operative times (OTs) were the main drivers against a widespread adoption of robot-assisted radical cystectomy (RARC). Despite acknowledged importance of attempting at performing i-UD following RARC,2 the extracorporeal urinary diversion (UD) accomplishment remains the most adopted approach after RARC. Perioperative blood transfusions have been considered a surrogate of surgical invasiveness; moreover retrospective evidence suggested a potential impact on survival outcomes in patients who undergo radical cystectomy (RC).3,4 To date, all the available randomized controlled trials (RCTs) were characterized by an extracorporeal approach in performing UD, undermining potential benefits of a totally minimally invasive procedure.5–8 There is only 1 other ongoing RCT aiming to compare open RC (ORC) and RARC with i-UD.9,10 Actually, high-level evidence supporting robotic RC is still lacking, and the scientific community needs to finally establish the role of a pure robotic approach in the surgical treatment of bladder cancer. In this study, we aimed to report perioperative and 6-month outcomes from the first single-center RCT comparing ORC and RARC with totally i-UD (Clinical Trials: NCT03434132). Material and Methods Study Design Institutional Review Board approval was obtained (IRB No. RS 824/16-N°0011123). Inclusion criteria were: diagnostic transurethral resection of bladder tumor with cT2-4, cN0, cM0 or recurrent BCG failure high-grade nonmuscle-invasive bladder cancer. Exclusion criteria were: anesthesiological contraindications to robotic surgery or palliative intent. Written informed consent was obtained from all patients. Randomization and Masking Patients were enrolled with a covariate adaptive randomization process based on the following variables: body mass index, ASA® (American Society of Anesthesiologists®) score, baseline hemoglobin (Hb) levels, planned UD (Padua ileal bladder or ileal conduit), neoadjuvant chemotherapy and cT-stage, via a web-based system “randPack,” “R” statistical software, exclusively managed by the Department of Clinical Trial Centre. Patients were allocated 1:1 in each group. Treatment allocation was only masked from pathologists who analyzed the cystectomy specimens. Procedures Previously standardized surgical procedures11,12 were performed by 2 surgical teams, both with an established experience for each surgical approach (more than 50 procedures per year in the last 2 years prior to enrolment). Robotic procedure meticulously replicated open surgical steps. Particularly, no hemostatic agents were used. The dorsal venous complex was controlled by 10 mm LigaSure™ (Covidien, Boulder, Colorado) in both cohorts. An extended pelvic lymph node dissection was performed up to aortic bifurcation in all patients.13 Nerve sparing in male and sex sparing in female patients were performed based on age, cT stage and baseline sexual functioning item. Health-related QoL (HRQoL) outcomes were obtained by self-assessed questionnaires (European Organisation for Research and Treatment of Cancer [EORTC]-QLQ-C30 and QLQ-BLM30), collected at baseline and 6 months after surgery.14,15 Time to role functioning was described as number of days from surgery to daily-life work activities recovery, and it was collected as indirect cost. Outcomes The primary end point was to demonstrate the superiority of RARC with i-UD in terms of a 50% overall transfusion rate reduction. A standardized approach for blood transfusions was assessed, intra- and postoperatively, when Hb levels were lower than 8 g/dl. Among secondary end points we aimed to investigate perioperative outcomes (within hospital stay [HS]), 30-, 90- and 180-day complication rates (reported by Clavien-Dindo classification16), global costs analysis, and 6-month functional, oncologic and HRQoL outcomes. Patients were defined day- and nighttime continent if they used ≤1 pad per day. Statistical Analysis Based on previously reported institutional data,17,18 we estimated a 50% transfusion rate in ORC cohort, aiming to test a transfusion rate halving on RARC cohort (25%). Using Chi-Square test, a sample of 116 patients, 58 for each cohort, will test the hypothesis with a 5% significant difference and 80% of power. Non-normally distributed continuous and categorical variables were compared using Kruskal-Wallis and Fisher exact tests, respectively. The Kaplan-Meier method and the log-rank test were applied to assess survival and functional outcomes. Patients were censored after 6 months of followup or at last followup for patients lost to followup. Normally distributed HRQoL continuous variables were compared with paired t test.15,19 A generalized linear mixed effect regression (GLMER) model including a random effect at the patient level was implemented to test differences in variation of HRQoL items along time (from baseline to 6 months) between groups. Significance threshold was set at p <0.05. Statistical analysis was performed using the Statistical Package for Social Science (SPSS®, IBM®, v.22.0, Armonk, New York). Results Between January 2018 and September 2020, 274 patients were admitted to our department and scheduled for RC; of these, 96 were excluded due to palliative intent. Out of 178 patients assessed for eligibility, 62 denied consent to randomization; therefore, 116 consecutive patients were finally enrolled, resulting in a 65% eligibility rate. At 6 months, 2 patients were lost to followup (unreachable), 1 for each cohort (see CONSORT-diagram in supplementary material, https://www.jurology.com), with a negligible impact on results. In the robotic group, UD was conducted in all cases with a totally intracorporeal approach, with no need of open conversion. A nerve/sex-sparing approach was performed in 14 patients (8 RARC vs 6 ORC; p=0.78). HRQoL domains scores were homogeneously distributed at baseline between groups (table 1). Table 1. Baseline features of 58 RARC cases and 58 ORC cases Clinical Features RARC ORC Median yrs age (IQR) 64 (53–70) 66 (58–71) No. male (%) 44 (76) 40 (69) Median kg/m2 body mass index (IQR) 26 (23–28) 26 (24–29) No. anticoagulant therapy (%) 13 (22) 12 (21) No. Charlson Comorbidity Index (%): 2 7 (12) 6 (10) 3 16 (28) 11 (19) 4 16 (28) 22 (38) 5 12 (21) 13 (22) 6 6 (10) 5 (9) 7 1 (2) 1 (2) No. ASA score (%): 1 2 (3) 2 (3) 2 43 (74) 50 (86) 3 13 (22) 6 (10) Median gm/dl baseline hemoglobin (IQR) 13.3 (12.3–14.2) 13.3 (11.5–14.8) No. neoadjuvant chemotherapy (%) 23 (40) 22 (38) No. neobladder UD (%) 46 (79) 42 (72) No. cT-stage (%): cTa/Tis 4 (7) 5 (9) cT1 7 (12) 7 (12) cT2 45 (78) 44 (76) cT3 2 (3) 2 (3) Mean±SD baseline EORTC QoL: Global health status/QoL 72.1±21.3 67.4±24.4 Functional scales: Physical functioning 92.3±15.5 89.5±15.8 Role functioning 86.2±22.1 90.8±19.0 Emotional functioning 81.1±19.4 78.0±23.6 Cognitive functioning 92.2±14.7 91.7±16.0 Social functioning 86.5±20.8 87.4±18.8 Symptoms scale: Fatigue 15.3±18.0 21.1±21.1 Nausea + vomiting 3.4±8.1 4.0±13.7 Pain 12.1±19.7 13.2±23.7 Dyspnea 7.5±15.3 9.8±16.5 Insomnia 16.1±24.4 17.8±28.8 Appetite loss 6.9±13.6 9.7±22.5 Constipation 10.9±18.1 15.5±25.9 Diarrhea 5.2±15.0 1.1±6.1 Financial difficulties 13.8±25.0 13.2±20.7 Urinary symptoms and problems 22.7±23.1 18.7±23.1 Future perspective 43.7±24.4 39.2±26.3 Abdominal bloating + flautulence 19.5±21.0 16.1±19.2 Body Image 13.7±20.3 13.7±17.2 Sexual functioning 44.9±31.0 41.3±32.1 The overall perioperative transfusion rates were significantly lower in the RARC cohort (22% RARC vs 41% ORC; p=0.046), while no significant differences were observed intra- and postoperatively. The absolute risk reduction was 19% (95% CI 2–36). No patient received transfusion outside the standardized approach (Hb levels <8 g/dl). Moreover, statistically significant differences were observed in terms of estimated blood loss (EBL) and 24-hour mean Hb variation (Δ Hb). Homogenous distribution of clinical stages turned into homogenous distribution of pT and pN stages, with comparable clearance of pelvic lymph nodes. Overall, readmission rates were comparable at 30 days, 90 days and 180 days, as well as complication rates, either for low- or high-grade complications (table 2). Table 2. Pathological data, perioperative and postoperative outcomes for 58 RARC cases and 58 ORC cases RARC ORC p Value Pathological data No. pT stage (%): 0.78 pTa 1 (2) 1 (2) pT0 15 (26) 20 (35) pT1 9 (12) 7 (12) pTis 3 (5) 2 (3) pT2a 3 (5) 6 (10) pT2b 6 (10) 3 (5) pT3a 5 (9) 4 (7) pT3b 11 (19) 12 (21) pT4a 5 (9) 2 (3) pT4b 0 1 (2) No. pN stage (%): 0.91 pN0 50 (86) 50 (86) pN1 2 (3) 3 (5) pN2 4 (7) 4 (7) pN3 2 (3) 1 (2) Median node status (IQR): Lymph node count 31 (22–38) 31 (22–38) 0.73 Lymph node density 0 (0–0) 0 (0–0) 0.83 Surgical margins 0 0 1 Periop outcomes Transfusions: No. overall periop (%) 13 (22) 24 (41) 0.046 Median units of blood transfused (IQR) 0 (0–0) 0 (0–2) 0.034 No. intraop (%) 3 (5) 6 (10) 0.49 Median intraop units of blood transfused (IQR) 0 (0–0) 0 (0–0) 0.31 No. postop (%) 13 (22) 23 (40) 0.07 Median postop units of blood transfused (IQR) 0 (0–0) 0 (0–1) 0.057 Median ml EBL (IQR) 401 (243–511) 467 (330–625) 0.020 % Δ Hb (IQR) −21 (−26–−14) −26 (−31–−17) 0.010 Median mins operative time (IQR) 313 (270–340) 190 (174–210) <0.001 No. adherence to Enhanced Recovery After Surgery protocol (%) 46 (79) 48 (83) 0.81 No. nasogastric tube placement (%) 12 (21) 10 (17) 0.81 Median days time to flatus (IQR) 3 (2–4) 3 (2–4) 0.75 Median days time to bowel (IQR) 5 (4–5) 5 (4–6) 0.74 Median days time to mobilization (IQR) 1 (1–2) 1 (1–2) 0.12 Median days time to regular diet (IQR) 4 (3–4) 4 (3–5) 0.52 No. periop complications (%): 21 (36) 29 (50) 0.19 Clavien 1-2 19 (33) 29 (50) 0.09 Clavien 3-5 5 (9) 1 (2) 0.21 Median days hospital stay (IQR) 7 (6–9) 6 (5–8) 0.22 Postop outcomes* No. days readmission (%) 30 7 (12) 5 (9) 0.76 90 16 (28) 12 (21) 0.51 180 19 (33) 14 (25) 0.41 No. 30-day complications (%): 10 (18) 10 (18) 1 Clavien 1-2 9 (16) 9 (16) 1 Clavien 3-5 2 (4) 2 (4) 1 No. 90-day complications (%): 24 (42) 25 (44) 1 Clavien 1-2 18 (32) 24 (42) 0.33 Clavien 3-5 9 (16) 6 (11) 0.58 No. 180-day complications (%): 28 (49) 32 (56) 0.57 Clavien 1-2 21 (37) 30 (53) 0.13 Clavien 3-5 16 (28) 9 (16) 0.17 Bolded values are significant at p <0.05. Postoperative outcomes were available for 114 patients (57 RARC vs 57 ORC). At 6 months, no differences were reported in terms of daytime continence, while the open cohort showed a higher nighttime continence probability (fig. 1). Figure 1. Kaplan-Meier curves for functional outcomes. The blue line represents patients who underwent RARC, and the red line those who underwent ORC. Day continence: log-rank p=0.25. Night continence: log-rank p=0.03. Particularly, at a median followup of 6 months (IQR 6–6), 9 patients (5 RARC vs 4 ORC) died within 6 months after surgery, of whom 6 died of disease (4 RARC vs 2 ORC). At Kaplan-Meier analysis, 6-month cancer-specific survival, overall survival and disease-free survival probabilities were comparable between groups (fig. 2). Figure 2. Kaplan-Meier curves for early survival outcomes. The blue line represents patients who underwent RARC, and the red line those who underwent ORC. CSS, cancer-specific survival (log-rank p=0.42). OS, overall survival (log-rank p=0.75). DFS, disease-free survival (log-rank p=0.98). At 6-month followup, HRQoL assessment was available for 106 patients (52 RARC vs 54 ORC). Overall, both cohorts experienced a significant worsening in terms of physical functioning, role functioning, fatigue, constipation, abdominal bloating and flatulence, body image and sexual functioning. On the one hand, patients who received ORC were more likely to experience dyspnea, appetite loss, diarrhea and urinary symptoms and problems. On the other hand, patients who received RARC reported a significant worsening of future perspective. Notwithstanding, at GLMER, surgical approach had a negligible impact on all HR-QoL domains (table 3). Table 3. EORTC QoL—longitudinal assessment at 6 months of followup for 52 RARC cases and 54 ORC cases Mean RARC±SD p Value* Mean ORC±SD p Value* GLMER (baseline–6 mos) RARC vs ORC Baseline 6 Mos Baseline 6 Mos p Value† Global health status/QoL 71.9±21.3 67.2±19.9 0.20 69.4±22.5 69.8±21.1 0.94 0.52 Functional scales: Physical functioning 91.6±16.1 83.3±20.2 0.004 90.2±15.6 76.7±23.5 <0.001 0.43 Role functioning 87.8±20.4 80.1±23.6 0.035 91.4±17.9 75.0±30.3 <0.001 0.36 Emotional functioning 82.3±16.9 78.2±20.5 0.14 79.2±22.9 75.2±26.5 0.31 0.97 Cognitive functioning 91.9±15.3 91.3±16.3 0.79 92.3±15.4 88.3±22.8 0.17 0.53 Social functioning 85.9±20.9 81.7±23.9 0.24 87.3±18.6 82.7±25.3 0.15 0.94 Symptoms scale: Fatigue 15.6±18.3 24.2±22.6 0.008 19.1±20.2 30.4±26.9 0.002 0.67 Nausea + vomiting 3.2±8.1 4.2±15.8 0.71 4.3±14.2 4.9±16.4 0.81 0.94 Pain 10.9±18.9 10.3±20.7 0.83 11.7±22.1 17.6±26.4 0.13 0.41 Dyspnea 8.3±15.9 12.2±20.9 0.20 8.6±14.7 22.8±28.8 <0.001 0.28 Insomnia 16.0±25.1 16.6±25.9 0.85 16.0±28.0 24.7±29.1 0.09 0.41 Appetite loss 6.4±13.3 8.9±22.0 0.47 8.0±21.4 14.8±27.2 0.040 0.54 Constipation 11.5±18.5 28.8±34.3 0.004 13.6±24.7 25.3±30.3 0.007 0.57 Diarrhea 4.5±13.2 8.3±19.7 0.24 1.23±6.4 6.2±14.6 0.010 0.82 Financial difficulties 12.8±23.0 19.9±29.7 0.09 13.6±21.0 22.8±30.9 0.050 0.78 Urinary symptoms + problems‡ 22.1±21.8 24.9±18.3 0.54 15.2±17.4 28.2±21.6 0.001 0.53 Future perspective 42.7±24.2 31.5±29.9 0.008 36.4±24.2 34.6±26.3 0.66 0.36 Abdominal bloating + flatulence 20.5±21.3 13.4±21.1 0.040 16.1±19.4 27.5±24.7 0.007 0.18 Body Image 13.8±21.1 24.8±29.3 0.006 13.5±16.7 31.3±27.8 <0.001 0.43 Sexual functioning 46.9±30.6 26.4±26.9 <0.001 42.4±32.1 18.5±21.4 <0.001 0.73 Bolded values are significant at p <0.05. Normally distributed HRQoL continuous variables were compared with paired t test. A GLMER model including a random effect at the patient level was implemented to test differences in variation of HRQoL items along time (from baseline to 6 months) between groups. 6-month assessment of urinary symptoms and problems was available for 79 patients (39 RARC vs 40 ORC). Actual hospital costs were obtained directly from the hospital administration: cost of operating room was 31€ per minute, while cost for HS was 832€ per day, and 400€ for each unit of blood transfusion. Direct costs per intensive care unit (ICU) day was 1,168€. The Italian mean daily wage was used to quantify cost of role functioning.20 Overall, total costs were significantly higher in the RARC cohort as a result of higher surgical devices and operative room costs. In line with the primary endpoint of the study, the RARC cohort described lower transfusion costs, while comparable costs were observed for hospital and ICU stay. Related to readmission costs, no differences were observed in terms of operative room, HS and ICU stay. Eventually, costs related to worsening of role functioning were comparable between groups (table 4). Table 4. Costs analysis for 58 RARC cases and 58 ORC cases Median RARC (IQR) Median ORC (IQR) p Value Perioperative costs (€): Surgical devices 8,471 (7,143–10,040) 1,757 (1,384–2,272) <0.001 Operative room 9,765 (8,355–10,579) 5,890 (5,386–6,510) <0.001 Hospital stay 5,824 (4,992–7,488) 4,992 (4,160–6,864) 0.22 ICU recovery 0 (0–0) 0 (0–0) 0.08 Transfusions 0 (0–0) 0 (0–800) 0.034 Readmission costs (€):* ICU recovery 0 (0–0) 0 (0–0) 0.16 Hospital stay 0 (0–2,496) 0 (0–0) 0.43 Operative room 0 (0–0) 0 (0–0) 0.16 Role functioning (€)* 4,800 (2,400–9,600) 4,800 (2,400–7,200) 0.53 Total costs (€) 31,886 (27,687–39,384) 20,102 (15,936–25,264) <0.001 Bolded values are significant at p <0.05. Costs analysis was performed on 114 patients (57 RARC vs 57 ORC). Discussion To the best of our knowledge, this is the first RCT aimed at comparing ORC vs RARC with i-UD. To date, all the available RCTs were characterized by an extracorporeal approach in performing UD, undermining potential benefits of a totally minimally invasive procedure.5–8 Gill et al previously highlighted limits of the available RCTs, reporting noncomparable learning curves between RARC and ORC, as well as a selection bias, due to a low level of patients accrual (25% of eligible patients).21 Therefore, an RCT comparing ORC and RARC with i-UD was long awaited in order to obtain stronger evidences. The available RCTs agree in reporting advantages of RARC in terms of reduced blood loss, at cost of longer OT, while slight differences occurred between trials in all the other perioperative outcomes. Bochner et al highlighted the advantage of RARC in terms of EBL (RARC 500 ml vs ORC 681 ml; p=0.012), confirming longer OT (RARC 464 vs ORC 330 minutes; p <0.001).6 In contrast, Khan et al did not confirm the advantage of RARC in terms of EBL (RARC 585 ml vs ORC 808 ml; p=0.070), even if a trend towards significance was observed.7 Finally, the RAZOR trial showed the advantage of RARC in terms of EBL (RARC 300 ml vs ORC 700 ml; p <0.0001), describing lower intra- (RARC 13% vs ORC 34%; p <0.0001) and postoperative (RARC 25% vs ORC 40%; p=0.0089) transfusion rates.8 Our study confirmed significantly lower transfusions rates in the RARC cohort, with comparable intraoperative and a trend towards significantly lower postoperative transfusion rates. The clinical significance of lower transfusion rate was underlined by the absolute risk reduction (19%; 95% CI 2–36), which described the net benefit of RARC in terms of transfusion rates. Despite lower transfusion rates in the ORC cohort compared to our previous experience,17,18 we confirmed the expected benefit of a totally minimally invasive procedure in terms of lower transfusion rates in the RARC arm. Moreover, significantly lower EBL and 24-hour Hb level drop were reported, undeniably confirming a benefit in preventing perioperative surgical bleeding in favor of RARC with i-UD. As expected, RARC with i-UD was confirmed to be time consuming compared with ORC, even if OT of RARC with i-UD was shorter than in previously reported extracorporeal series. More interestingly, perioperative complications rates were comparable between groups both for low- and high-grade complications, confirming feasibility and safety of RARC with i-UD. Despite a slightly higher readmission rate in the RARC cohort, we reported comparable postoperative complications rates for both low- and high-grade complications. Notably, when restricting analysis to neobladder complication rates, we observed 44% and 41% in robotic and open neobladders, respectively. These data compare favorably with 58% 90-day complication rates reported in a large open series from a tertiary referral center.22 Eventually, overall intraoperative and postoperative complication rates were largely comparable to those observed in the RARC with extracorporeal UD series,7,8 supporting safety and feasibility of a totally intracorporeal approach. The available RCTs did not report any functional outcome of orthotopic neobladder, misevaluating one of the main aspects of a continent UD. We previously reported 2-year functional outcomes of patients who underwent robotic intracorporeal Padua ileal bladder, describing 73% and 56% of day- and nighttime continence probabilities, respectively.23 Recently, Satkunasivam et al reported urodynamic and urinary function outcomes, comparing RARC with i-UD and ORC.24 Despite comparable complete continence rates between cohorts, fewer than 1 patient out of 5 achieved complete continence recovery. Moreover, the study described worst outcomes of the robotic approach in terms of day- and nighttime pad use and size, and daytime pad wetness. On the contrary, we observed comparable daytime continence recovery probabilities between cohorts, while at 6-month evaluation lower nighttime continence rates were observed in patients receiving robotic neobladder. Concerning pathological outcomes, this trial confirmed effectiveness of both ORC and RARC, being nodal clearance and incidence of soft tissue positive surgical margins comparable between arms. Preliminary analysis of oncologic outcomes was reported to highlight comparable survival curves, therefore minimizing the impact of disease recurrence on HRQoL outcomes. Short followup precludes drawing conclusions about superiority of one approach over the other. Actually, the available RCTs reporting HRQoL comparison between RARC and ORC showed no significant differences,5–8 suggesting a negligible role of surgical approach on HRQoL. In a previous report, we found equivalence between RARC-i-UD and ORC for all HRQoL domains except for minor items, namely insomnia and abdominal bloating and flatulence.25 When restricting analysis to the first 6-month followup, we confirmed the noticeable impact of RC on self-assessed HRQoL. Both groups experienced a significant worsening in terms of physical, role and sexual functioning, associated with a remarkable impact on body image, abdominal bloating and flatulence, fatigue and constipation. On the one hand, patients who underwent ORC were more likely to experience a major HRQoL decline, particularly in terms of a higher impairment of symptoms scale, as well as a significant worsening of urinary symptoms and problems. On the other hand, the RARC cohort showed an unexpected significant worsening on future perspective. However, no difference was found between groups at analysis of variation along time, supporting negligible role of surgical approach on HRQoL outcomes also in the early postoperative course. There is growing interest in costs of robotic surgery and sustainability for health care providers. The evidence related to global costs analysis between RARC and ORC is still lacking. While it has been demonstrated that the overall costs for ORC are lower than for RARC, previous analyses did not account for the effectiveness of RARC and the minimally invasive technology with regard to patient-centered outcomes. In a decision analytical model by Kukrejia et al, RARC was found to be cost-effective compared to ORC when the rates of a complication can be prevented 74% of the time or as long as it is 70% effective in preventing a transfusion.26 In our study, RARC was confirmed to have higher perioperative costs in terms of surgical devices and operative room, while potential benefits of RARC with i-UD in terms of lower readmission or role functioning costs were not observed. Similar costs related to length of HS and return to daily activities did not mitigate the impact of surgery related costs on global costs assessment. The present study is not devoid of limitations. First, the study was performed in a single high-volume referral center, and surgical procedures were performed by 2 surgical teams, both with an established experience either for ORC or RARC. Furthermore, the rates of neobladder are higher than those reported in general practice; therefore, results obtained may not be widely generalizable. Finally, longer followup is mandatory to assess potential differences between groups with regard to oncologic and functional outcomes. Conclusions This prospective randomized trial observed 22% and 41% overall perioperative transfusion rates in RARC- and ORC-treated patients, respectively, confirming a significant benefit in favor of RARC with i-UD. However, perioperative complications, HS and 6-month HRQoL were largely comparable between groups. Oncologic and functional outcomes will be assessed at longer followup to observe potential differences between arms. Acknowledgments The authors acknowledge the Italian Ministry of Health “Ricerca Finalizzata 2016.” References 1. : Robotic-assisted surgery for the treatment of urologic cancers: recent advances. Expert Rev Med Devices 2020; 17: 579. Google Scholar 2. : Best practices in robot-assisted radical cystectomy and urinary reconstruction: recommendations of the pasadena consensus panel. Eur Urol 2015; 67: 363. Google Scholar 3. : Association between perioperative blood transfusions and clinical outcomes in patients undergoing bladder cancer surgery: a systematic review and meta-analysis study. J Blood Transfus 2016; 2016: 9876394. Google Scholar 4. : Impact of perioperative blood transfusions on clinical outcomes in patients undergoing surgery for major urologic malignancies. Ther Adv Urol 2019; 11: 1756287219868054. Google Scholar 5. : Prospective randomized controlled trial of robotic versus open radical cystectomy for bladder cancer: perioperative and pathologic results. Eur Urol 2010; 57: 196. Google Scholar 6. : Comparing open radical cystectomy and robot-assisted laparoscopic radical cystectomy: a randomized clinical trial. Eur Urol 2015; 67: 1042. Google Scholar 7. : A single-centre early phase randomised controlled three-arm trial of open, robotic, and laparoscopic radical cystectomy (CORAL). Eur Urol 2016; 69: 613. Google Scholar 8. : 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. Google Scholar 9. : Robot-assisted radical cystectomy with intracorporeal urinary diversion versus open radical cystectomy (iROC): protocol for a randomised controlled trial with internal feasibility study. BMJ Open 2018; 8: e020500. Google Scholar 10. : Robot-assisted versus open cystectomy in the RAZOR trial. Lancet 2019; 393: 644. Google Scholar 11. : Risk assessment of stone formation in stapled orthotopic ileal neobladder. J Urol 2016; 193: 891. Google Scholar 12. : Robotic intracorporeal padua ileal bladder: surgical technique, perioperative, oncologic and functional outcomes. Eur Urol 2018; 73: 934. Google Scholar 13. : Stage-specific impact of extended versus standard pelvic lymph node dissection in radical cystectomy. Int J Urol 2013; 20: 390. Google Scholar 14. : The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85: 365. Google Scholar 15. : EORTC QLQ-C30 Scoring Manual. EORTC 2001. Available at https://www.eortc.org/app/uploads/sites/2/2018/02/SCmanual.pdf. Google Scholar 16. : Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240: 205. Google Scholar 17. : Analysis of radical cystectomy and urinary diversion complications with the Clavien classification system in an Italian real life cohort. Eur J Surg Oncol 2013; 39: 792. Google Scholar 18. : Perioperative and mid-term oncologic outcomes of robotic assisted radical cystectomy with totally intracorporeal neobladder: results of a propensity score matched comparison with open cohort from a single-centre series. Eur J Surg Oncol 2018; 44: 1432. Google Scholar 19. : General population normative data for the EORTC QLQ-C30 health-related quality of life questionnaire based on 15,386 persons across 13 European countries, Canada and the Unites States. Eur J Cancer 2019; 107: 153. Google Scholar 20. JobPricing: JP Salary Outlook 2021—L' Aanalisi del Mercato Retributivo Italiano. 2021. Available at www.jobpricing.it. Accessed November 23, 2021. Google Scholar 21. : The devil is in the details: randomized trial of robotic versus open radical cystectomy. Eur Urol 2015; 67: 1053. Google Scholar 22. : Lessons learned from 1,000 neobladders: the 90-day complication rate. J Urol 2010; 184: 990. Link, Google Scholar 23. : Robotic intracorporeal Padua ileal bladder: surgical technique, perioperative, oncologic and functional outcomes. Eur Urol 2018; 73: 934. Google Scholar 24. : Robotic intracorporeal orthotopic neobladder: urodynamic outcomes, urinary function, and health-related quality of life. Eur Urol 2016; 69: 247. Google Scholar 25. : Comparison of patient-reported health-related quality of life between open radical cystectomy and robot-assisted radical cystectomy with intracorporeal urinary diversion: interim analysis of a randomised controlled trial. Eur Urol Focus 2021. https://doi.org/10.1016/j.euf.2021.03.002. Google Scholar 26. : Cost-effectiveness of robot-assisted radical cystectomy using a propensity-matched cohort. Eur Urol Focus 2020; 6: 88. Google Scholar Support: Italian Ministry of Health “Ricerca Finalizzata 2016.” Conflict of Interest: The authors declare no competing interests. Ethics Statement: Institutional Review Board approval was obtained (IRB No. RS 824/16-N°0011123). Author Contributions: All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. RM and GS have accessed and verified the data. Data Availability: The deidentified database, study protocol, statistical analysis plan and informed consent form will be made available “with publication.” Clinical Trials Registration: NCT03434132. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.© 2022 The Author(s). Published on behalf of the American Urological Association, Education and Research, Inc.FiguresReferencesRelatedDetailsCited byMastroianni R, Ochoa Arvizo M, Torregiani G and Simone G (2022) Robot-assisted vs Open Radical Cystectomy: Randomized Controlled Trials Lights and ShadowsJournal of Urology, VOL. 209, NO. 3, (460-461), Online publication date: 1-Mar-2023.Related articlesJournal of Urology18 Feb 2022Editorial Comment Volume 207Issue 5May 2022Page: 982-992Supplementary Materials Advertisement Copyright & Permissions© 2022 The Author(s). Published on behalf of the American Urological Association, Education and Research, Inc.Keywordsrobotic surgical procedurescystectomyurinary bladder neoplasmsrandomized controlled trialAcknowledgmentsThe authors acknowledge the Italian Ministry of Health “Ricerca Finalizzata 2016.”MetricsAuthor Information Riccardo Mastroianni IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy *Correspondence: IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Via Elio Chianesi 53, 00154, Rome (RM), Italy telephone: 0652665005—+393404016868; FAX: 0652666823; email: E-mail Address: [email protected] More articles by this author Mariaconsiglia Ferriero IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy More articles by this author Gabriele Tuderti IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy More articles by this author Umberto Anceschi IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy More articles by this author Alfredo Maria Bove IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy More articles by this author Aldo Brassetti IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy More articles by this author Leonardo Misuraca IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy More articles by this author Ashanti Zampa IRCCS “Regina Elena” National Cancer Institute, Department of Clinical Trial Centre, Biostatistics and Bioinformatics, Rome, Italy More articles by this author Giulia Torregiani IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy More articles by this author Edoardo Ghiani IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy More articles by this author Diana Giannarelli IRCCS “Regina Elena” National Cancer Institute, Department of Clinical Trial Centre, Biostatistics and Bioinformatics, Rome, Italy More articles by this author Salvatore Guaglianone IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy More articles by this author Michele Gallucci IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy More articles by this author Giuseppe Simone IRCCS “Regina Elena” National Cancer Institute, Department of Urology, Rome, Italy More articles by this author Expand All Support: Italian Ministry of Health “Ricerca Finalizzata 2016.” Conflict of Interest: The authors declare no competing interests. Ethics Statement: Institutional Review Board approval was obtained (IRB No. RS 824/16-N°0011123). Author Contributions: All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. RM and GS have accessed and verified the data. Data Availability: The deidentified database, study protocol, statistical analysis plan and informed consent form will be made available “with publication.” Clinical Trials Registration: NCT03434132. Advertisement Advertisement PDF downloadLoading ...
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