The RAZOR trial is the first randomized (1:1) phase 3 study comparing survival outcomes of non-metastatic high-risk non-muscle invasive and muscle invasive bladder cancer patients treated with robotic assisted radical cystectomy (RARC) versus open radical
cystectomy (ORC) with concomitant bilateral pelvic lymph node dissection (Figure 1) . The primary aim of this non-inferiority trial was to compare 2-yr progression-free survival (PFS). Between 2011 and 2014, 159 and 153 patients were included in
the intention-to-treat analysis and underwent RARC or ORC, respectively. All patients were treated with extracorporeal urinary diversion. Patients were randomly allocated by institutions (n = 15) and stratified by urinary diversion type, cT stage
and Eastern Cooperative Oncology Group (ECOG) performance status. Surgeons who participated in the study were required to have performed at least 10 RARC or ORC procedures in the year before the study. A non-inferiority margin of 15% points was considered
on the basis of available literature on the topic. Baseline characteristics were similar between the groups, and 2-yr PFS was 72.3% in the RARC versus 71.6% in the ORC arm, showing non-inferiority of RARC to ORC (0.7% difference, 95% confidence interval:
9.6% to 10.9%; p = 0.9) (Figure 2). No differences were reported as well when considering secondary outcomes such as overall and high-grade complications, surgical margin rates and quality of life according to a patient reported outcome measures.
Figure 1. Flowchart depicting the inclusion of the patients in the RAZOR trial.
Figure 2. Kaplan-meier curves depicting progression-free survival in the per-protocol and modified intention to treat analysis stratified by approach.
The European Association of Urology guidelines support robotic surgery for radical cystectomy on the basis of previous published feasibility trials showing evidence of lower estimated blood loss, transfusion rates and shorter hospital stays against longer
operative time for RARC compared to ORC [2-4]. These trials selectively focused on perioperative and functional outcomes [3,4]. However, oncological outcomes had not yet been assessed in a randomized controlled fashion in the setting of radical cystectomy.
The RAZOR trial reports non-inferior PFS at 2 yr for patients undergoing RARC, with no differences in secondary outcomes (overall and high-grade complications, PSM rates, and quality of life according to a patient-reported outcome measure) . The
results of this trial support strongly the use of RARC, however some limitations need to be highlighted.
1. Selection bias
Approximately seven patients per center per year were included in this trial, which very likely represents only a marginal proportion of all cystectomy candidates referred to the participating centers . Several questions arise. How many patients were
treated with ORC or RARC at each center over the time period of the trial? What were the demographic, clinical, and tumor characteristics, and, importantly, the oncological and functional outcomes for off-trial compared with on-trial patients? The
external validity of the findings could be significantly undermined by these selection biases. Real life patients and outcome may differ from the trial setting
2. Local recurrence
Although no difference in the patterns of local and distant recurrences was observed between the two groups in this trial, in another single-center RCT comparing RARC versus ORC, at longer follow-up (median 4.9 yr for patients still alive) there was a
significantly higher rate of pelvic/abdominal recurrences in the RARC arm .
3. Treatment modalities choice
Patients in the RARC group had higher rate of adjuvant chemotherapy (whereas the ORC group was more likely to receive neoadjuvant chemotherapy). Moreover, differences in the choice of lymphadenectomy templates were reported between the two groups. These
differences may have impacted the oncological outcomes of the patients independently from the type of surgical aproach.
4. Extracorporeal diversion
All patients were treated with extracorporeal diversion reconstruction. Differences might exist for patients treated with intracorporeal diversion reconstruction, which appears to be the new gold standard for RARC.
 Parekh DJ, Reis IM, Castle EP, 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 Jun 23;391(10139):2525-2536. doi: 10.1016/S0140-6736(18)30996-6.
 Witjes JA, Lebret T, Compérat EM, et al. Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer.
Eur Urol 2017;71:462–75.
 Bochner BH, Dalbagni G, Sjoberg DD, et al. Comparing open radical cystectomy and robot-assisted laparoscopic radical cystectomy: a randomized clinical trial.
Eur Urol 2015;67:1042–50.
 Nix J, Smith A, Kurpad R, Nielsen ME, Wallen EM, Pruthi RS. Prospective randomized controlled trial of robotic versus open radical cystectomy for bladder cancer: perioperative and pathologic results.
Eur Urol 2010;57:196–201.
 Bochner BH, Dalbagni G, Marzouk KH, et al. Randomized trial comparing open radical cystectomy and robot-assisted laparoscopic radical cystectomy: oncologic outcomes.
Eur Urol. In press. https://doi.org/10.1016/j.euru…