iROC Trial: Robot-assisted Cystectomy Boosts Survival

In patients with bladder cancer, undergoing robot-assisted surgery for radical cystectomy brought about a significantly greater number of days alive and out of hospital compared with open surgery, according to results of the iROC trial, published in JAMA.

In the randomized iROC trial, Catto and colleagues sought to assess recovery and morbidity after robot-assisted radical cystectomy with intracorporeal reconstruction in patients with nonmetastatic bladder cancer and compare results with those achieved via open radical cystectomy. They enrolled 338 patients from nine sites in the U.K., whom they randomized to one of these treatments.

"Radical cystectomy included removal of the prostate and seminal vesicles in men and the uterus, fallopian tubes, and vaginal wall (with or without one or both ovaries) in women, as detailed. The urethra was preserved in women receiving neobladder reconstruction," explained James W. F. Catto, PhD, of the University of Sheffield, Sheffield, England, and colleagues from the iROC Study Team.

"Open surgery was performed through a lower midline incision. Robotic surgery was performed using a da Vinci surgical robot (various models were used across the centers) and included robotic cystectomy and reconstruction," they added.

Data from 305 patients were analyzed for the primary outcome of the study, which was the number of days alive and out of hospital within 90 of surgery. Secondary outcomes included 20 variables such as quality of life, complications, and survival. Patients were followed at 90 days, 6 months, and 12 months, with a final follow-up on Sept. 23, 2021.

Most patients were men (79%), with a mean age of 69 years. Six percent were older than 80, and most were current or ex-smokers. Most patients (79%) had urothelial carcinoma, and before radical cystectomy, 34% of patients received neoadjuvant chemotherapy. Muscle-invasive bladder cancer was cystectomy confirmed in 44%, non-grade non-muscle-invasive disease in 30%, and no residual cancer in 14%.

In patients undergoing robotic surgery, the median number of days alive and out of hospital within 90 days of surgery was 82 days, compared with 80 for those undergoing open surgery (adjusted difference: 2.2 days; 95% CI: 050-3.85; P=0.01).

At 5 weeks, patients undergoing robotic surgery also reported better quality of life compared with those undergoing open surgery (difference in WHO Disability Assessment Schedule 2.0 scores: 0.48; 95% CI: 0.15-0.73; P=0.003). But by 12 weeks, the differences were not significant (difference: 0.38; 95% CI: 009-0.68; P=0.01).

Also by week 5, disability scores worsened 2.2-fold in patients undergoing robotic surgery, compared with 2.87-fold for open surgery. Patients treated with open surgery had significantly more disability compared with robotic surgery patients (difference in WHODAS 2.0 scores: 0.43; 95% CI: 0.15-0.73; P=0.003). At 12 weeks, this difference was 0.38 (95% CI: 0.09-0.68; P=0.01), but by 26, the differences in disability scores were no longer significant.

Also by 12 weeks, complications had occurred in 63.4% of patients in the robotic surgery group, compared with 67.9% of those in the open surgery group. Patients who underwent robotic surgery were also less likely to have thromboembolic complications compared with those undergoing open surgery (1.9% versus 8.3%, respectively; difference: −6.5%; 95% CI: −11.4% to −1.4%), and wound complications (5.6% versus 16.0%; difference: −11.7%; 95% CI: −18.6% to −4.6%).

At a median of 18.4 months of follow-up, Catto and fellow researchers found no significant differences in cancer recurrence (18% versus 16%, respectively) or overall mortality (14.3% versus 14.7%) between patients undergoing robotic surgery versus open surgery.

In their accompanying editorial, Avinash Maganty, MD, and colleagues stressed the importance of these results, adding that its design differed from previous trials in three significant ways. First, Catto et al used a composite measure of recovery to measure early postoperative recovery.

"This composite measure of recovery is important because the benefits of robotic surgery are perceived to be realized in the period soon after surgery," they noted.

Second was researchers’ use of Enhanced Recovery After Surgery (ERAS) protocols in both groups, which included thromboprophylaxis, early postoperative mobilization, avoidance of bowel preparation, and preoperative calorific drinks. Third, patients treated with robotic surgery underwent an "intracorporeal approach to urinary diversion, maximizing any potential benefits of a completely minimally invasive approach."

Ultimately, they concluded "[t]he study by Catto and colleagues in JAMA is an important milestone for robotic surgery, as it is among the first to demonstrate a benefit in a multicenter clinical trial. Whether the benefit in days spent outside of the hospital is clinically meaningful and sufficient to promote further diffusion is likely to be a source of debate, with rational arguments on both sides of quality and cost issues. Nonetheless, robotic surgery is here to stay. Further similar trials in other disease contexts are warranted to refine robotic surgery’s niche in the surgical armamentarium to maximize its value to patients."

Study limitations include that the trial was closed early and adherence to in-person endpoint measurements was compromised due to the pandemic, that the primary outcome may be questioned, that results may not be generalizable to low-volume hospitals, that the primary outcome included medical events controlled by unblinded clinicians, low adherence to wearable activity trackers, the imbalance between groups in patients who did not undergo surgery or were excluded after cystectomy, and the need for longer-term follow-up of oncologic outcomes.

The University College London sponsored this study. This work was funded by grants from The Urological Foundation and The Champniss Foundation. Robotic consumables were supplied at no cost by Intuitive Surgical.

Catto is funded by an NIHR research professorship, and reported receiving reimbursement for consultancy from AstraZeneca, Ferring, Roche, and Janssen; speaker fees from Bristol Myers Squibb, Merck Sharp & Dohme, Janssen, Astellas, Nucleix, and Roch.e; honoraria for membership in advisory boards from Ferring, Roche, Gilead, Photocure, Bristol Myers Squibb, QED Therapeutics, and Janssen; and research funding from Roche

Maganty reported no disclosures.

Catto JWF, 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" JAMA 2022; DOI: 10.1001/jama.2022.7393.

Maganty A, Herrel LA, Hollenback BK "Robotic surgery for bladder cancer" JAMA 2022; DOI: 10.1001/jama.2022.6417.