Open radical cystectomy (ORC) remains a gold standard for the treatment of invasive bladder cancer. It has unparalleled local control and the best long-term oncologic outcomes. It is associated with significant morbidity, which can be reduced with contemporary management and enhanced recovery after surgery (ERAS) pathways. It entails a steep learning curve and outcomes improve with experience.
Prior successful experience with minimally invasive techniques (robotic prostatectomy) without compromising oncologic outcomes, has resulted in a growing interest in applying these skills to invasive bladder cancer.
Usage of robotic radical cystectomy (RARC) has increased in recent years from less than 10% in 2008 to more than 20% in 2012, according to the SEER/Medicare database. A study from the National Cancer Database (NCDB) has also shown a growing trend with RARC representing almost 40% of all cystectomies in 2013.1 This was favored in lower volume and non-academic centers.
Dr. Cookson moved on to compare RARC to ORC with regards to oncologic outcomes, morbidity, learning curve, and cost. In a meta-analysis of 19 studies, ORC was compared to RARC. This meta-analysis included 2 randomized controlled trials, 10 prospective trials, and 7 retrospective studies.2 The meta-analysis demonstrated no difference in surgical margins, but RARC was shown to result in a significantly higher lymph node yield than ORC. This important comparison of oncological outcomes resulted in the publication of the well-known and recently published randomized controlled trial, the RAZOR trial.3 This study randomized and compared ORC to RARC, with the primary endpoint being 2-year progression-free survival (PFS), with non-inferiority established if the lower bound of the one-sided 97.5% CI for the treatment difference (RARC-ORC) was greater than 15%. The 2-year PFS was 72.3% in RARC compared to 71.6% in ORC, p=0.001. This led to the conclusion that RARC was non-inferior to ORC for 2-year PFS.
ORC is a high-risk operation with a high complication rate of approximately 30%, and a mortality rate of around 3%. A large study assessed the 90-day readmission, morbidity, and mortality of ORC in a contemporary series. A total of 753 consecutive patients undergoing radical cystectomy between 2001-2007 were assessed.4 The results demonstrated a readmission rate of 20-27% and a mortality rate of 2-7%.
Supporters of minimally invasive approaches claim that this modality diminishes operative morbidity and results in less blood loss, reduced pain, shorter length of stay, fewer complications, and improved health-related quality of life. This also led to a randomized controlled study comparing outcomes and complications between ORC and RARC.5
In this randomized controlled trial, 60 patients who underwent RARC were compared to 58 patients who underwent ORC. The results demonstrated a similar complication rate (62% vs. 66%, p=0.66), a similar length of hospital stay, but a shorter operative time for RARC. This trial received some criticism due to the fact that all urinary diversion was done extracorporeally, and this was not a real comparison between RARC and ORC. Additionally, the accrual rate was quite low, at around 25% (raising concerns regarding pragmatism). Furthermore, the comparative experience of the robotic surgeon vs. the open surgeon is largely unknown to most readers. Lastly, the blood transfusion rate was not included in the analysis. A large meta-analysis compared the complication rate of RARC and ORC, showing a benefit favoring RARC.
If the complications are mainly attributed to bowel and urinary infections, then current available randomized controlled trials did not answer whether the urinary diversion has an advantage. Another important issue raised is whether the Clavien system is appropriate, as ileus and small bowel obstruction are not clearly manifested in this system. It remains unclear whether intracorporeal diversion offers a lower complications rate than an extracorporeal diversion. There is some data demonstrating that intracorporeal diversion compared to extracorporeal diversion results in a significant reduction of 90-day complications.6 In an attempt to answer this question, there is currently an ongoing randomized controlled trial comparing ORC to RARC with intracorporeal diversion.7 Other novel outcomes that will be measured in this trial will include perioperative outcomes, oncologic outcome, quality of life, quantified activity, and surgeon fatigue.
In conclusion, the oncologic outcomes are non-inferior thus far when comparing ORC to RARC. RARC is associated with less blood loss, shorter length of stay, and less pain. The learning curve for RARC is acceptable, but the cost is higher. Results of future ongoing studies will reveal more information, and perhaps cause RARC to replace ORC, as the new gold standard.
Presented by: Michael Cookson, MD, Professor and Chairman of the Department of Urology at the University of Oklahoma Health Sciences Center, and holds the Donald D. Albers Endowed Chair in Urology, Oklahoma City, Oklahoma
References:
1. Bachman AG. et al. Minimally Invasive Versus Open Approach for Cystectomy: Trends in the Utilization and Demographic or Clinical Predictors Using the National Cancer Database. Urology. 2017 May;103:99-105.
2. Wang XL. et al.miR-378b Promotes Differentiation of Keratinocytes through NKX3. PLoS One. 2015 Aug 27;10(8):e0136049.
3. Parekh DJ. 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.
5. Bochner BH. et al. Comparing Open Radical Cystectomy and Robot-assisted Laparoscopic Radical Cystectomy: A Randomized Clinical Trial. Eur Urol. 2015 Jun;67(6):1042-1050.
6. Ahmed K et al.Analysis of intracorporeal compared with extracorporeal urinary diversion after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium. Eur Urol. 2014 Feb;65(2):340-7.
7. Catto JWF et al. Robot-assisted radical cystectomy with intracorporeal urinary diversion versus open radical cystectomy (iROC): protocol for a randomised controlled trial with internal feasibility study. BMJ Open. 2018 Aug 8;8(8):e020500.