There has been significant controversy over the adoption of robotic surgery for cystectomy with intracorporeal diversion over the traditional open radical approach. In a recent report published in JAMA by researchers in England—“Effect of robot-assisted radical cystectomy with intracorporeal urinary diversion vs open radical cystectomy on 90-day morbidity and mortality among patients with bladder cancer: a randomized clinical trial”—Catto and colleagues aimed to demonstrate that robotic surgery yields superior morbidity and mortality outcomes for patients in the first few months after surgery.1
The researchers began by noting that the standard of care for nonmetastatic aggressive bladder cancer is radical cystectomy with pelvic lymphadenectomy.2 Many variables are prognostic for survival after surgery, including cancer characteristics, optimal therapy, and preoperative patient health. Radical cystectomy is associated with postoperative complications, and 20% to 30% of patients will be readmitted to hospital for a complication that occurs after discharge.3 Multiple factors have been, or are currently being investigated to reduce perioperative and postoperative complications. Among these are improvements in surgical technique and early recovery after surgery (ERAS) protocols.4
The RAZOR Trial
The pivotal RAZOR trial has thus far reported similar oncologic outcomes at 2 years after surgery with fewer perioperative setbacks (including lower blood loss, less transfusions, and shorter postoperative hospitalizations), although the procedures took more time. 5 The limitation of the RAZOR trial, however, was that patients who had robotic-assisted radical cystectomy underwent extracorporeal urinary diversion via an open incision. Thus, the aim of the present study was to compare a total intracorporeal robot-assisted radical cystectomy with open radical cystectomy.
The study was a phase 3, multicenter, unblinded, randomized trial that recruited patients between March 2017 and March 2020. The hypothesis was that a total intracorporeal robotic-assisted radical cystectomy would be associated with a faster recovery time and fewer days in the hospital when compared to open radical cystectomy. Among the inclusion criteria were age over 18 years, classification as a good surgical candidate for both robotic and open approaches, a diagnosis of nonmetastatic bladder cancer, and an Eastern Cooperative Oncology Group (ECOG) status score of 1-3.
Among the exclusion criteria were a history of previous abdominal or pelvic surgery, or radiation therapy. Surgeons involved in the study were using ERAS protocols, including thromboprophylaxis, early postoperative mobilization, avoiding bowel preparation, and preoperative calorific drinks. Surgeons had to have completed at least 30 previous radical cystectomies independently. Other standard requirements included urethral preservation, when appropriate for neobladder reconstruction, and minimal necessary lymphadenectomy.
Primary outcomes were days alive and out of hospital within 90 days of surgery, postoperative duration of hospital stay, readmission rate, and deaths within 90 days. Among the secondary outcomes explored were rates of complications and adverse events up to 90 days, overall survival, oncologic outcomes (including recurrence-free survival, cancer-free survival, and metastasis-free survival), and health-related quality of life outcomes (assessed via patient questionnaires and with use of a wristband pedometer to evaluate patient activity). These outcomes were rigorously monitored at set intervals throughout the follow-up period. The authors noted that several secondary outcomes were not investigated in this study—including rates of admission to intensive care, conversion to an open approach, need to convert to extracorporeal urinary diversion, and surgeon fatigue. The study was powered to detect a difference of at least 2 days of postoperative hospital stay.
After screening, 338 patients were randomized to the 2 arms. After randomization, some patients did not undergo a cystectomy or underwent the approach of the other arm. In all, 157 patients underwent robotic-assisted radical cystectomy and 149 patients underwent open radical cystectomy. Participants were balanced with respect to demographic and disease factors. Nearly 80% of patients were male (mean age, 69 years) and most had a history of smoking (71%). A total of 34% of patients in each arm underwent neoadjuvant chemotherapy before surgery; 44% of patients had confirmed muscle-invasive bladder cancer, 30% had high- grade non–muscle-invasive bladder cancer, and 14% had no residual disease. At the time of surgery, nearly 90% of patients underwent ileal conduit reconstruction.
Study Results
A total of 29 surgeons were involved in the study. Mean operative time was 4.9 hours for the robotic arm versus 4.5 hours for the open arm. Intraoperative blood loss was approximately 200 mL for patients in the robotic cohort versus 550 mL for the open cohort. Intraoperative transfusion rates were 2.6% for the robotic cohort versus 6.5% for the open cohort. Intraoperative visceral injuries were rare in both groups.
The median number of days out of hospital and alive was 82 days for the robotic cohort versus 80 days for the open cohort. Median length of postoperative hospitalization was 7 days in the robotic cohort versus 9 days for the open cohort. Readmission rates were 21.8% in the robotic cohort versus 32.2% in the open cohort. Results for length of time when readmitted were similar between the groups. Death occurred in 2 patients in the robotic cohort (attributed to cardiorespiratory failure and cancer progression) and 4 patients in the open cohort (2 attributed to intra-abdominal sepsis/laparotomy/organ failure, 1 attributed to pulmonary embolus, and 1 due to cancer progression).
Findings for the secondary outcome of complications were reported as follows: 63.4% of patients experienced a complication in the robotic arm versus 67.9% in the open arm; 67% of complications were Clavien-Dindo grade 2 or less, and severity was similar between the 2 arms. Of note, compared with the open radical cystectomy arm, patients who underwent robotic surgery had fewer wound-related complications (5.6% vs 17.3%), thromboembolic complications (1.9% vs 8.3%), and a lower rate of blood transfusion (7% vs 12%). At 5 weeks, patients who had undergone open surgery reported worse health-related quality of life, but by 12 weeks, scores for the groups were similar.
Study Survival Outcomes
Disability scores, measured via patient-reported questionnaire, were worse in the open surgery group at week 5 (2.2-fold vs 2.9-fold) and were significantly different at that time and at week 12; however, at week 26, there was no significant difference. There also was no significant difference in physical activity, as measured by pedometer, between the 2 study arms. Strength and stamina, as measured by physical activity at interval follow-ups, initially were statistically significant and superior in the robotic arm at weeks 5 and 12. However, at week 26, there was no significant difference between the cohorts.
The authors also reported on oncological and survival outcomes. At the median follow-up time of 18.4 months, the rate of cancer recurrence was 18% in the robotic arm versus 16% in the open arm. Death rates within 90 days of surgery were 1.2% in the robotic arm versus 2.6% in the open arm. No port site recurrences were reported. All-cause mortality was not statistically significant (14.3% for the robotic arm vs 14.7% for the open arm).
In their discussion, the authors noted that although the results indicate that robotic-assisted intracorporeal diversion led to statistically significant improvement in 90-day mortality for patients with nonmetastatic bladder cancer, the clinical importance of these findings remains uncertain.
Several previous studies have shown that robotic surgery offers benefits over open surgery for both the surgeon and patient, but this report highlights advantages that occur after surgery in the immediate postoperative period. Intracorporeal reconstruction has potential to advance the minimally invasive approach by reducing incision, and theoretically reduce operative time, but with the cost of technical challenge and a possibly higher learning curve. However, these outcomes support the benefits of shorter hospitalization times and lower readmission rates, while potentially improving immediate surgical recovery through less disability, greater stamina, and lower rates of thromboembolism.
Some of the study limitations mentioned by the authors included lack of inpatient follow-up, owing to restrictions related to the COVID-19 pandemic. The study sites included high-volume centers, which may limit generalizability to community settings. The unblinded nature of the trial also may have introduced bias.
In summary, this study of great interest to the urologic community, showed that use of a robotic-assisted intracorporeal approach to treatment of patients with nonmetastatic bladder cancer resulted in a statistically significant increase in 90-day postoperative mortality when compared with the standard open radical approach. A longer follow-up study will be required to assess oncologic outcomes.
David Ambinder, MD is a urology resident at New York Medical College / Westchester Medical Center. His interests include surgical education, GU oncology and advancements in technology in urology. A significant portion of his research has been focused on litigation in urology.
References
- Catto JWF, Khetrapal P, Ricciardi F, et al; for the iROC Study Team. Effect of robot-assisted radical cystectomy with intracorporeal urinary diversion vs open radical cystectomy on 90-day morbidity and mortality among patients with bladder cancer: a randomized clinical trial. [Online ahead of print.] 2022. doi: 10.1001/jama.2022.7393
- Witjes JA, Bruins HM, Cathomas R, et al. European Association of Urology Guidelines on Muscle-invasive and metastatic bladder cancer: summary of the 2020 guidelines. Eur Urol. 2021;79(1):82-104. doi: 1016/j.eururo.2020.03.055
- Williams SB, Cumberbatch MGK, Kamat AM, et al. Reporting radical cystectomy outcomes following implementation of enhanced recovery after surgery protocols: a systematic review and individual patient data meta-analysis. Eur Urol. 2020;78(5):719-730. doi: 1016/j.eururo.2020.06.039
- Pang KH, Groves R, Venugopal S, Noon AP, Catto JWF. Prospective Implementation of Enhanced Recovery After Surgery Protocols to Radical Cystectomy. Eur Urol. 2018 Mar;73(3):363-371. doi: 1016/j.eururo.2017.07.031
- Parekh DJ, Reis IM, Castle EP, Gonzalgo ML, Woods ME, Svatek RS, Weizer AZ, Konety BR, Tollefson M, Krupski TL, Smith ND, Shabsigh A, Barocas DA, Quek ML, Dash A, Kibel AS, Shemanski L, Pruthi RS, Montgomery JS, Weight CJ, Sharp DS, Chang SS, Cookson MS, Gupta GN, Gorbonos A, Uchio EM, Skinner E, Venkatramani V, Soodana-Prakash N, Kendrick K, Smith JA Jr, Thompson IM. 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. PMID: 29976469.
