EAU 2019: Healthy Male Patient Undergoing Radical Cystectomy, Undecided on Diversion: Robotic

Barcelona, Spain (UroToday.com) In the Common Problems in Muscle Invasive and Advanced Bladder Cancer: Evidence-Based Debates session at the 2019 European Association of Urology meeting EAU 2019, Dr. Juan Palou presented the following case to facilitate the debate between Drs. Agarwal and Lerner titled: "Healthy Male Patient Undergoing Radical Cystectomy, Undecided on Diversion: Open or Robotic?"  The patient case was as follows: a 63-year-old journalist with a BMI of 29, who presented with hematuria and irritative symptoms. His hemoglobin was 13.5 gr/L, with a GFR of 75; ultrasonography revealed a 4.5 cm bladder tumor on the right lateral wall, which was confirmed on CT scan. There was no visible extravesical disease and no hydronephrosis. A complete TURBT was performed, as well as several additional biopsies of the bladder – pathology revealed cT2 high grade urothelial carcinoma and carcinoma in situ on the posterior wall. A biopsy of the prostatic urethra was negative and a radical cystectomy was proposed after receiving gemcitabine/cisplatin neoadjuvant chemotherapy.

Dr. Piyush Agarwal offered a rebuttal to Dr. Seth Lerner’s presentation, advocating for robotic-assisted radical cystectomy for this patient. He started by acknowledging a recently published New England Journal of Medicine trial that showed that minimally invasive radical hysterectomy was associated with lower rates of disease-free survival and overall survival than open abdominal radical hysterectomy among women with early-stage cervical cancer 1. This lead to the following statement from the FDA “To evaluate robotically-assisted surgical devices for use in the prevention or treatment of cancer, including breast cancer, the FDA anticipates these uses would be supported by specific clinical outcomes, such as local cancer recurrence, disease-free survival, or overall survival at time periods much longer than 30-days.”

In Dr. Agarwal’s opinion, we have this data – the RAZOR trial 2. This trial was a randomized, open-label, non-inferiority, phase 3 trial done in 15 medical centers in the USA. Eligible patients were ≥18 years of age, had biopsy-proven clinical stage T1-T4, N0-N1, M0 bladder cancer or refractory carcinoma in situ. Patients were centrally assigned (1:1), to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion. The primary endpoint was 2-year progression-free survival, with non-inferiority established if the lower bound of the one-sided 97.5% CI for the treatment difference (robotic cystectomy minus open cystectomy) was greater than -15 percentage points. There were 350 patients, including 176 undergoing robotic cystectomy and 174 undergoing open cystectomy. 302 patients (150 in the robotic cystectomy group and 152 in the open cystectomy group) were included in the per-protocol analysis set. The 2-year progression-free survival was 72.3% (95%CI 64.3-78.8) in the robotic cystectomy group and 71.6% (95%CI 63.6-78.2) in the open cystectomy group (difference 0.7%, 95%CI -9.6%-10.9%), indicating non-inferiority of robotic cystectomy. Adverse events occurred in 101 (67%) of 150 patients in the robotic cystectomy group and 105 (69%) of 152 patients in the open cystectomy group. 

Dr. Agarwal notes that in the RAZOR trial there was no difference in the quality of life, 90-day complication rates, or positive surgical margin rates. In his opinion, judicious bagging of the specimens (bladder and lymph nodes) ensures that suspect recurrence patterns that have been reported are a non-issue. Because the RAZOR trial did all extracorporeal diversions, he notes that he is part of the iROC trial that will answer the question of intracorporeal diversion. He thinks that the findings to date suggest that the mode of surgery does not influence outcomes as significantly as do the surgeons themselves.

Dr. Agarwal concluded his presentation advocating for robotic-assisted radical cystectomy with several statements:
  • Oncologic outcomes are not inferior for robotic-assisted radical cystectomy (but remember to bag the bladder and lymph nodes)
  • Robotic-assisted radical cystectomy is associated with less blood loss and shorter hospital stay
  • Robotic-assisted radical cystectomy is associated with difficult reproducibility and is somewhat difficult to teach; as of now it is more expensive than open radical cystectomy
  • The skill set developed performing robotic-assisted radical cystectomy allows one to perform more complicated reconstructive cases such as partial cystectomy, Boari flap, and ureteral reimplantation
  • Surgical ergonomics for robotic-assisted radical cystectomy and comfort should lead to career longevity
  • As urologists and pioneers of innovation and technology in surgery, we must continue to fulfill this role

Presented by: 
Juan Palou, MD, Ph.D., FEBU, the University Autonoma of Barcelona, Barcelona, Spain
Piyush K. Agarwal, MD, the National Cancer Institute, Bethesda, Maryland

Written by:  Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University - Medical College of Georgia Twitter: @zklaassen_md at the 34th European Association of Urology (EAU 2019) #EAU19 conference in Barcelona, Spain, March 15-19, 2019.

References:
1. Ramirez PT, Frumovitz M, Pareja R, et al. Minimally invasive versus Abdominal Radical Hysterectomy for Cervical Cancer. N Engl J Med 2018 Nov 15;379(20):1895-1904.
2. 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, randomized, phase 3, non-inferiority trial. Lancet 2018 Jun 23;391(10139):2525-2536.

Further Related Content: Healthy Male Patient Undergoing Radical Cystectomy, Undecided on Diversion: Open