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ERUS 2018: Do We Need to Change Selection Criteria for Advanced Disease in the Era of Neoadjuvant Chemotherapy: Open Radical Cystectomy or Robotic Radical Cystectomy

Marseille, France (UroToday.com) This was a debate on the topic of what surgical modality (open or robotic radical cystectomy) should be performed in advanced bladder cancer, and whether neoadjuvant chemotherapy (NAC) has any effect on the decision made.

Dr. Witjes began the debate and explained why only open radical cystectomy (ORC) should be used in advanced bladder cancer cases, after receipt of NAC. Dr. Witjes began this discussion by questioning why NAC should even influence the decision what kind of surgical modality should be used. It is known that many factors affect what kind of definitive surgical therapy patients should receive. These include patient age, comorbidities, kidney function, patient’s quality of life, previous surgeries and more. However, NAC is usually not regarded as one of the influencing factors.

According to the most recent EAU guidelines, NAC should be offered to bladder cancer patients with clinical stage T2-T4a, N0M0 disease. Usually, this should be given in the form of cisplatin-based combination chemotherapy. Unfortunately, to date, there are no known tools to help select patients who would most benefit from NAC. Another problematic issue is the cisplatin ineligibility of patients. This can be due to impaired renal function, impaired performance status, and increased age. This leads us to question whether NAC is even effective in real life patients? Outside of the world of clinical trials. A study analyzing 8732 patients from the National Cancer Database (NCDB) between the years 2004 and 2012, showed that 1619 patients received NAC1. The patients who received NAC had a higher percentage of PT0, but no overall survival benefit was evident. The authors concluded that in real life patients, NAC did not show any survival advantage.

Dr. Witjes gave two reasons why NAC has no benefit in the current era.

  1. The modern extended pelvic lymph node dissection improves survival. Currently, there are two ongoing randomized controlled trials: the SWOG trial and the German AUA-LEA trial attempting to figure out what pelvic lymph node dissection is needed to improve oncological outcomes.
  2. The chemotherapy that was analyzed in the randomized controlled trial assessing NAC in bladder cancer patients was MVAC and not GEM-CIS. MVAC was retrospectively shown to be more effective than GEM-CIS2, resulting in a higher rate of complete response and overall survival.
Dr. Witjes stated that the guidelines regarding NAC in bladder cancer are based on studies from the nineties of the last century, and they have not been updated. According to him, we would not be able o get the same advantage of 5% improved overall survival in the current era. This is because in 2018 the chemotherapy regimen given to patients is slightly less effective, and our surgeries are more effective, with an improved lymph node dissection.

In the RAZOR trial3, comparing ORC to robotic radical cystectomy (RARC), RARC was shown to have less blood loss and a shorter length of stay (by one day). However, ORC was shown to have a shorter operating time and was less costly. Most importantly, the complication rate, oncological endpoints, and six months reported quality of life were similar in both surgical modalities.

There is some data showing that the quality of RARC with intracorporeal urinary diversion (UD) is not as good as that shown in ORC. This manifests as neobladders with lower volumes, and more continence issues. Additionally, a study has shown that RARC with intracorporeal UD compared to extracorporeal UD was associated with higher grade complications4. There are also some reports that RARC can result in port site metastasis and unexpected early recurrences5, 6

Dr. Witjes concluded his talk and stated that no matter what surgical modality is chosen, according to the EAU guidelines,  they must be done in a high volume experienced center.

Dr. Wiklund from the Karolinska Institute in Sweden then debated why RARC should be performed in advanced bladder cancer, after receipt of NAC.

Dr. Wiklund began by showing the results of the European Urology study published in 2015, showing the long-term results of patients who underwent RARC7. This study demonstrated that patients who underwent RARC have acceptable long-term survival. The small randomized trial from Memorial Sloan Kettering comparing RARC to ORC demonstrated no difference in the overall survival rates8. Moreover, the larger but similar RAZOR trial also did not show any difference in the oncological outcomes between RARC and ORC3. A study comparing the recurrence rates between ORC and RARC showed the RARC did not have a higher recurrence rate compared to ORC9.

Dr. Wiklund concluded his presentation and stated that RARC is a safe oncological procedure, with no evidence demonstrating it to be inferior to ORC. It has comparable cancer-specific survival, positive surgical margin rates, and lymph node counts as ORC.  Lastly, the evidence demonstrating any association between RARC and unusual recurrence patterns is poor.

The data we have to date does not show any advantage of one modality over the other.

 
Presented by: F. Witjes, Nijmegen, the Netherlands

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter:@GoldbergHanan at the EAU Robotic Urology Section (ERUS) Meeting - September 5 - 7, 2018 - Marseille, France

References:

  1. Hanna N, Trinh Q-D, Seisen T, et al. Effectiveness of Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer in the Current Real World Setting in the USA. European Urology Oncology 2018; 1(1): 83-90.
  2. Zargar H, Shah JB, van Rhijn BW, et al. Neoadjuvant Dose Dense MVAC versus Gemcitabine and Cisplatin in Patients with cT3-4aN0M0 Bladder Cancer Treated with Radical Cystectomy. The Journal of Urology 2018; 199(6): 1452-8.
  3. 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 (London, England) 2018; 391(10139): 2525-36.
  4. Hussein AA, May PR, Jing Z, et al. Outcomes of Intracorporeal Urinary Diversion after Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium. The Journal of Urology 2018; 199(5): 1302-11.
  5. Albisinni S, Fossion L, Oderda M, et al. Critical Analysis of Early Recurrence after Laparoscopic Radical Cystectomy in a Large Cohort by the ESUT. The Journal of Urology 2016; 195(6): 1710-7.
  6. Jancke G, Aljabery F, Gudjonsson S, et al. Port-site Metastases After Robot-assisted Radical Cystectomy: Is There a Publication Bias? European Urology 2018; 73(4): 641-2.
  7. Raza SJ, Wilson T, Peabody JO, et al. Long-term oncologic outcomes following robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium. European Urology 2015; 68(4): 721-8.
  8. Bochner BH, Dalbagni G, Marzouk KH, et al. Randomized Trial Comparing Open Radical Cystectomy and Robot-assisted Laparoscopic Radical Cystectomy: Oncologic Outcomes. European Urology 2018.
  9. Nguyen DP, Al Hussein Al Awami B, Wu X, et al. Recurrence patterns after open and robot-assisted radical cystectomy for bladder cancer. European Urology 2015; 68(3): 399-405.