Multi-Institutional Analysis of Robotic Radical Cystectomy for Bladder Cancer: Perioperative Outcomes and Complications in 227 Patients

Introduction

Radical cystectomy remains one of the most effective oncological treatments for patients with muscle-invasive bladder cancer and for those with high-grade, recurrent, noninvasive tumors. ¹ Over the past several years, robotic cystectomy has begun to emerge as a viable alternative to open radical cystectomy, and several retrospective case series have been published to confirm acceptable surgical and perioperative results.^2–5 From these studies, potential benefits of laparoscopic and robotic approaches include less surgical blood loss, early return of bowel function, less analgesic requirement, and more rapid postoperative convalescence.

We originally reported our initial experience with this approach in 2007. ⁶ In this carefully selected cohort of men undergoing robotic-assisted laparoscopic radical cystoprostatectomy, we observed acceptable operative, pathological, and short-term clinical outcomes. Based on this initial evidence, we anticipated increased refinement of surgical technique and reduced operating room time. Over the ensuing years, we broadened the application of this approach to female patients and more complex cases. Recently, we reported our most recent data, evaluating the most recent cohort of 100 consecutive patients undergoing robotic cystectomy and confirming acceptable surgical and pathological outcomes. ⁷

As several single-center studies have now reviewed the operative and perioperative outcomes associated with this novel technique, our objective has now widened to provide multi-center evidence of the applicability and adequate surgical and perioperative outcomes associated with robotic radical cystectomy, which has yet to be published in the literature. Herein, we report our multi-institutional, multi-surgeon experience with robot-assisted laparoscopic radical cystectomy with regard to operative and pathologic outcomes and complications to evaluate the feasibility and reproducibility of this technique in a large cohort of patients with bladder cancer.

Subjects and Methods

In accordance with the principles and practices of the University of North Carolina (Chapel Hill, NC) institutional review board, and in recognition of and compliance with the U.S. Health Insurance Portability and Accountability Act of 1996 guidelines, a retrospective review was performed of our bladder cancer database at the University of North Carolina as well as that of three other institutions, including the University of Alabama (Birmingham, AL), Mayo-Scottsdale (Scottsdale, AZ), and Tulane University (New Orleans, LA). Representing surgeons on different levels of their respective learning curve, 227 consecutive patients (178 males, 49 females) were identified who underwent robot-assisted laparoscopic radical cystectomy and urinary diversion for clinically localized urothelial carcinoma of the bladder from January 2006 to October 2009. These 227 patients represent a multi-institutional, multi-surgeon experience with the robot-assisted approach to radical cystectomy from their first case to their most mature experience. Patient characteristics are shown in Table 1. All patients underwent preoperative laboratory work, imaging studies (chest x-ray, abdominal pelvic cross-sectional imaging), and endoscopic resection (i.e., transurethral bladder tumor resection). Surgical technique with regard to robot-assisted radical cystectomy has been previously described. ⁸

Outcome measures evaluated in this multi-institutional series include operative variables (total surgical time and estimated blood loss), aspects of hospital recovery (time to hospital discharge), pathologic outcomes (pathologic stage, margin status, occurrence of bladder entry, and number of lymph nodes removed), and 30-day complication rates. Complications were measured using the Clavien–Dindo classification system.^9,10 This system is well established in the general surgery and urologic literature and provides a more standardized approach to the reporting of complications across different institutions.^11,12

Statistical analysis for evaluation of complications was performed using SAS version 9.2 (SAS Institute, Cary, NC). Univariate analysis was used using Fisher's exact test for categorical variables and t test for continuous variables. Multivariate analysis was carried out via logistic regression, assessing complication rate as the dependent variable, controlling for the covariates of age, sex, American Society of Anesthesiologists (ASA) score, body mass index, and stage. Multiple models were fitted, including several other covariates that proved nonsignificant and were thus dropped from the model. These included estimated blood loss, margin status, operative time, neoadjuvant chemotherapy, and type of diversion.

Results

Mean age of the 227 patients was 67.1 years (range, 33–86 years) with a male-to-female ratio of 3.6:1. Mean ASA score was 2.7 (median 3). The majority of cases (n=136, 60%) were clinical stage T2, followed by cT1 or less (n=69, 31%), cT3 or cT4 (n=18, 8%), and node positive (n=2, 0.9%). As shown in Table 1, 168 patients underwent an ileal conduit diversion, 58 received orthotopic ileal neobladder, and 1 had no diversion due to anuric end-stage renal disease.

Perioperative outcomes, listed in Table 2, were similar to those in single case-series published in the literature. Mean blood loss was approximately 256 mL, and length of stay was between 5 and 6 days, with 70% being discharged by day 5. Average operative time was approximately 5.5 hours. Regarding pathologic outcomes, 5 patients had a soft tissue margin on final pathology, one of which was from the abdominal wall due to extravesical disease. In addition, an inadvertent bladder entry occurred in 1 patient that was recognized intraoperatively without any gross urine spillage and was repaired. The mean number of lymph nodes removed was 18 (median, 18; range, 3–52). In the entire cohort, 120 patients (53%) had pathologically organ-confined disease (pT2 or less), with 30 patient having pT0 disease, 46 with pT1 or Tis, and 44 having pT2 disease. Thirty-five patients had extravesical disease (15%), whereas 46 (20%) had node-positive disease (pTxN+). In this series, 38 patients (17%) received neoadjuvant platinum-based chemotherapy.

In the perioperative period, the overall 30-day complication rate was 30%, with a total of 68 complications. Of these patients, 15 (7%) had a major complication (defined as Clavien grade 3 or higher) with no perioperative deaths in this series. Demonstrated in Table 3, univariate analysis using Fisher's exact test revealed a significant difference in patients with various ASA scores and length of stay between those with and without complications. There were no significant differences in age, body mass index, pathologic stage, margin status, or operative time when comparing those without complications with those with either minor or major complications.

Multivariate analysis was carried out via logistic regression, controlling for the covariates age, sex, ASA score, body mass index, and stage. Multiple models were fitted, including several other covariates that proved non-significant and subsequently dropped from the model. These included estimated blood loss, operative time, and type of diversion. In the final model, sex, clinical stage, body mass index, margin status, and neoadjuvant chemotherapy were nonsignificant with point estimates and confidence intervals shown in Table 4. Although age was nonsignificant on univariate analysis, it was significant when controlling for the above-mentioned variables, specifically when controlling for neoadjuvant chemotherapy. Age (stratified by age 65 years) was found to be a significant predictor (P=.0230) of worse complications, with those <65 years old being twice as likely to experience a higher Clavien complication rate with robotic surgery when controlling for other variables. ASA score was also likely to predict complications, with higher ASA scores associated with a higher Clavien complication rate (P=.0258). Those with an ASA score of 4 were 9 times more likely to have a complication than those with an ASA score of 2. Similarly, those with an ASA score of 3 were 2.5 times more likely to experience a complication compared with those with an ASA score of 2. Use of neoadjuvant chemotherapy also predicted complications, with a higher number of major complications compared with those who did not undergo chemotherapy.

Discussion

In recent years, many authors have described the feasibility of laparoscopic and robotic approaches to patients undergoing radical cystectomy for urothelial carcinoma of the bladder. Techniques have been described in the literature and, based on multiple single-institution case series, seem to replicate and perhaps improve upon the perioperative outcomes and complications of the gold standard approach of open radical cystectomy. Potential benefits of laparoscopic and robotic approaches include lower surgical blood loss, early return of bowel function, and more rapid postoperative convalescence. These early experiences have certainly demonstrated the feasibility of the procedure. However, these studies have been single-institution studies, often reflecting a single surgeon's experience.

The current series represents one of the largest clinical and multi-institutional case series of robotic radical cystectomy for the treatment of bladder cancer that evaluates perioperative outcomes and complications. The results of this study are important for several reasons. First and foremost, to attain widespread acceptance, the procedure must be feasible not only to surgeons with a long history of robotic experience but also to surgeons who are significantly lower on their learning curve. As outlined in a prior study, attaining success with respect to robotic cystectomy (in surgeons already proficient at robotic prostatectomy) may require at least 20–40 cases to attain proficiency with respect to blood loss and operative time. ¹³ This study demonstrates that the procedure is indeed feasible and safe, offering acceptable outcomes, even while including surgeons with less experience.

With regard to complications, we found that decreased age and increased ASA score were important predictors of subsequent complications. This finding is different than those of prior studies. For example, Kauffman et al. ¹⁴ performed a single-institution case series of patients undergoing robotic cystectomy and found that age ≥65 years as well as increased blood loss and intraoperative fluids were independent predictors of complications in this retrospective review. Our findings may be secondary to sample selection bias. For example, robotic cystectomy may be purposefully reserved for younger patients, and only the healthiest older patients are selected to undergo robotic cystectomy, thereby creating a selection bias that explains the increased complications noted in younger patients. Certainly, the limitations of a nonrandomized retrospective review may be considered in this regard.

Increased ASA score was a significant predictor of complications on multivariate analysis, and this finding has been corroborated by a single-institution retrospective review analyzing early complications after open radical cystectomy. ¹⁵ In this analysis, increasing ASA score and transfusion requirement were both independent predictors of subsequent complication, specifically those of higher Clavien score.

Comparing our remaining results to these prior studies, we found that blood loss, operative time, gender, and stage were not predictors. Whether the above-mentioned results are specific to the robotic technique is undetermined and will require a multi-institutional randomized study comparing these specific items. Furthermore, attempting to determine the comorbidity index in these patients would be beneficial, especially when attempting to explain the finding that younger patients experienced a higher number of complications in our multi-institutional cohort of patients.

This study has several noteworthy limitations. First, this is a descriptive study with regard to perioperative and pathologic factors. Certainly, evaluation of the mean values for lymph node count, length of stay, and operative time would be even better served in multivariate analyses comparing with open cystectomy. However, such a trial has not yet been completed. Second, this is a retrospective review and is therefore prone to the limitations inherent in this study design. Complication rates may not be accurately recorded because of the bias of record-keeping or loss of follow-up, and it is also recognized that the patients selected for robotic cystectomy may in fact be healthier than the usual cohort represented in open radical cystectomy series.

Nevertheless, this study does demonstrate the first multi-institutional analysis of complications and perioperative outcomes following robotic radical cystectomy and is an important addition to the literature as we continually reassess the validity of a novel oncologic technique. It is hoped that this will lead to a multi-institutional randomized trial that may shed more light on the most important question of oncologic outcome as well as validate the now well-established short-term perioperative outcomes associated with robotic cystectomy.

Conclusion

We describe a relatively large and maturing multi-institutional experience with robot-assisted radical cystectomy for the treatment of bladder cancer. The robotic approach to cystectomy appears to provide acceptable operative, pathological, and short-term clinical outcomes, which duplicate the principles and practices of the gold standard open technique. Demonstrating these findings in a multi-institutional cohort of patients now confirms the possible widespread applicability of the technique, confirming good results among a diverse cohort of surgeons and institutions with divergent experience. Still, it remains important to acknowledge that a prospective, randomized, multi-center trial will be required to determine whether this technique clearly offers advantages while offering feasibility and applicability among a range of surgeons and institutions.