iRARC adoption is slow but persistent in bladder cancer
"Over the past 10 to 15 years, tremendous efforts have gone into robotic surgical innovation to improve perioperative morbidity for patients with bladder cancer undergoing RC," write Andrew M. Wood, MD, and Nima Almassi, MD.
"Although a substantial learning curve exists, early level 1 evidence suggests that there is a benefit to perioperative morbidity and patient-reported outcomes [with iRARC]," write the authors.
Management of the 25% of patients with bladder cancer presenting with muscle-invasive disease at time of diagnosis requires an aggressive multimodal approach with extirpative surgery at its center.1 In patients with this aggressive form of bladder cancer, current American Urological Association and international guidelines recommend surgery to remove the bladder in its entirety. This would include removing the prostate and seminal vesicles in men; the uterus, cervix, and part of the vagina in women; and the pelvic lymph nodes.2,3 This procedure requires the creation of a urinary diversion, typically from a portion of the small intestine. This is a highly complex, technically challenging procedure that is performed in over 10,000 patients in the United States each year.4
In addition to the complexity of the surgery, perioperative care is complicated by the characteristics of a typical patient with bladder cancer. These characteristics include advanced age, higher likelihood of smoking, and presence of more comorbidities than the average patient.5,6 Because of these factors and the length and complexity of the surgery, radical cystectomy (RC) is associated with significant postoperative morbidity. Despite best efforts, complication rates at 30 and 90 days following RC range between 40% and 60% of patients, with 20% to 30% of patients requiring readmission after discharge.7,8 In an attempt to mitigate this substantial surgical morbidity, attempts at robot-assisted radical cystectomy (RARC) began in the early 2000s. Initial innovation began with a hybrid technique that combined robotic removal of the bladder with a traditional open approach to urinary diversion.9 Not long after the hybrid RARC began to take hold, surgeons began innovating techniques to perform the urinary diversion robotically, a technique referred to as total intracorporeal RARC (iRARC).
Over the past 5 to 10 years, a growing body of evidence has demonstrated the impact of these new techniques on both cancer control and perioperative outcomes. Early retrospective series focused on the more common hybrid approach to RARC and demonstrated encouraging results. However, it wasn’t until the recent publication of results from the phase 3 RAZOR trial (NCT01157676) that level 1 evidence regarding RARC became available. Begun in 2011 and published in 2018, the RAZOR trial randomly assigned patients to either hybrid RARC or traditional open RC.10 Two-year progression-free survival after RARC was noninferior to open RC, providing high-quality evidence that RARC is an oncologically sound procedure. However, the anticipated benefits of RARC on complication rates were largely absent, with no differences in overall adverse events between the two groups. As urologists suspected this lack of morbidity benefit was related to the open urinary diversion portion of the hybrid procedure, interest continued to grow in the iRARC approach.
A total intracorporeal approach to urinary diversion possesses several potential advantages over the traditional open approach. First, because bowel manipulation is done robotically, iRARC requires a substantially smaller incision than the hybrid approach, theoretically resulting in less pain, a lower incidence of wound complications such as hernia or infection, and less insensible fluid loss and fluid shifts during surgery. In addition, bowel exposure and manual handling are eliminated, potentially resulting in a quicker return of postoperative bowel function. Despite these theoretical advantages, retrospective studies examining perioperative outcomes have demonstrated mixed results and are often plagued by selection bias and issues with the iRARC learning curve.11,12
Fortunately, the first randomized data comparing iRARC with open RC were published in summer 2022 in the form of results from the iROC trial (NCT03049410). This investigator-initiated, phase 3, multicenter, randomized trial randomly assigned adult patients with nonmetastatic urothelial or variant carcinoma of the bladder electing RC as their primary management strategy to either an open RC or iRARC approach. Importantly, the trial required surgeons to be accredited and have performed at least 30 RC procedures of their chosen approach within the past year to participate in the trial. The median number of days alive and out of the hospital within 90 days of surgery was two fewer for iRARC vs open RC (82 vs 80 days; P=.01). Thromboembolic complications (1.9% vs 8.3%) and wound complications (5.6% vs 16%) were less common with iRARC vs open RC. Most importantly, patients in the iRARC cohort reported better quality of life vs open RC at 5 weeks and less disability at 5 weeks and 12 weeks. There were no further differences beyond 12 weeks in quality-of-life metrics. Finally, similar to the RAZOR trial, there were no statistically significant differences in cancer recurrence (18% after iRARC vs 16% after open RC) and overall mortality (14.3% vs 14.7%) at a median follow-up of 18.4 months.
Although the iROC trial provided level 1 evidence of the benefits of iRARC when it comes to postoperative morbidity and patient-centered outcomes, wide adoption remains slow, mostly because of an impressive learning curve. Although results from some studies have provided evidence that acceptable surgical proficiency may be attained in as few as 30 cases,14 results from a recent learning curve analysis published by the European Association of Urology Robotic Urology Section Scientific Working Group suggested that true proficiency may take a little longer. In fact, to reach plateau with regard to all measures of proficiency (major and overall complication rates, operative time, blood loss, and hospital length of stay), it took an average of almost 200 cases.15 Except for the highest volume surgeons, the average number of RC procedures performed annually ranges from 1 to 10.16 making the overall time investment to achieve proficiency prohibitive for most surgeons who did not learn iRARC in training.
In summary, over the past 10 to 15 years, tremendous efforts have gone into robotic surgical innovation to improve perioperative morbidity for patients with bladder cancer undergoing RC. These efforts have resulted in the development and slow but persistent adoption of the iRARC technique for robotic bladder removal and urinary diversion. Although a substantial learning curve exists, early level 1 evidence suggests that there is a benefit to perioperative morbidity and patient-reported outcomes. Further confirmatory studies are needed and would go a long way toward convincing more urologists to make the switch.
References
1. Chang SS, Bochner BH, Chou R, et al. Treatment of nonmetastatic muscle-invasive bladder cancer: American Urological Association/American Society of Clinical Oncology/American Society for Radiation Oncology/Society of Urologic Oncology clinical practice guideline summary. J Oncol Pract. 2017;13(9):621. doi:10.1200/JOP.2017.024919
2. Chang SS, Bochner BH, Chou R, et al. Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/ASTRO/SUO guideline. J Urol. 2017;198(3):552-559. doi:10.1016/j.juro.2017.04.086
3. 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:10.1016/j.eururo.2020.03.055
4. Arora S, Keeley J, Patel A, et al. Defining a “high volume” radical cystectomy hospital: where do we draw the line? Eur Urol Focus. 2020;6(5):975-981. doi:10.1016/j.euf.2019.02.001
5. Cumberbatch MGK, Jubber I, Black PC, et al. Epidemiology of bladder cancer: a systematic review and contemporary update of risk factors in 2018. Eur Urol. 2018;74(6):784-795. doi:10.1016/j.eururo.2018.09.001
6. Catto JWF, Downing A, Mason S, et al. Quality of life after bladder cancer: a cross-sectional survey of patient-reported outcomes. Eur Urol. 2021;79(5):621-632. doi:10.1016/j.eururo.2021.01.032
7. Maibom SL, Joensen UN, Poulsen AM, Kehlet H, Brasso K, Røder MA. Short-term morbidity and mortality following radical cystectomy: a systematic review. BMJ Open. 2021;11(4):e043266. doi:10.1136/bmjopen-2020-043266
8. 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:10.1016/j.eururo.2020.06.039
9. Menon M, Hemal AK, Tewari A, et al. Nerve‐sparing robot‐assisted radical cystoprostatectomy and urinary diversion. BJU Int. 2003;92(3):232-236. doi:10.1046/j.1464-410x.2003.04329.x
10. 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;391(10139):2525-2536. doi:10.1016/S0140-6736(18)30996-6
11. Hussein AA, Elsayed AS, Aldhaam NA, et al. A comparative propensity score-matched analysis of perioperative outcomes of intracorporeal vs extracorporeal urinary diversion after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium. BJU Int. 2020;126(2):265-272. doi:10.1111/bju.15083
12. Riveros C, Ranganathan S, Nipper C, et al. Open vs. robot-assisted radical cystectomy with extracorporeal or intracorporeal urinary diversion for bladder cancer: a pairwise meta-analysis of outcomes and a network meta- analysis of complications by urinary diversion approach. Can Urol Assoc J. Published online October 25, 2022. doi:10.5489/cuaj.8096
13. Catto JWF, Khetrapal P, Ricciardi F, et al. 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. JAMA. 2022;327(21):2092-2103. doi:10.1001/jama.2022.7393
14. Noh TI, Shim JS, Kang SG, Cheon J, Pyun JH, Kang SH. The learning curve for robot-assisted radical cystectomy with total intracorporeal urinary diversion based on radical cystectomy pentafecta. Front Oncol. 2022;12:975444. doi:10.3389/fonc.2022.975444
15. Wijburg CJ, Hannink G, Michels CTJ, et al. Learning curve analysis for intracorporeal robot-assisted radical cystectomy: results from the EAU Robotic Urology Section Scientific Working Group. Eur Urol Open Sci. 2022;39:55-61. doi:10.1016/j.euros.2022.03.004
16. McCabe JE, Jibawi A, Javle PM. Radical cystectomy: defining the threshold for a surgeon to achieve optimum outcomes. Postgrad Med J. 2007;83(982):556-560. doi:10.1136/pgmj.2007.058214
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