Recurrence patterns after open and robot-assisted radical cystectomy for bladder cancer - Beyond the Abstract

The ultimate governing factor in assessing the adoption of robot-assisted radical cystectomy (RARC) over open radical cystectomy (ORC), remains without a doubt oncologic safety and efficacy. Although previous studies had documented short-term recurrence rates after RARC, recurrence patterns were yet to be evaluated. In our study, we sought to analyze recurrence patterns within 2 years of surgery in patients undergoing RARC and ORC (1). We chose the 2-year limit because recurrences are a time-to-event outcome and most recurrences occur during this time period (2, 3).

The reported recurrence rates after RARC are heterogeneous among published studies; for instance a study from Nepple et al from Washington University consisting of 36 patients demonstrated 67% 2-year recurrence-free survival (RFS) probability after RARC (4). Another study from Sweden including 70 patients documented 81% RFS probability at the same time point (5). RFS probability in 263 patients who underwent RARC at our institution was 73% at 2 years. Discrepancy in recurrence rates can be attributed to differences in stage distribution, as the Swedish study included only 15% of patients with T3-T4 disease, compared to 48% in Nepple et al’s study and 34% in our study. Furthermore, we performed a multivariable Cox regression analysis to evaluate the association of surgical approach (RARC vs. ORC) and bladder cancer recurrence. We found that RARC was not independently associated with disease recurrence (Hazard ratio 0.78, 95% CI 0.5-1.21).

Similarly to previous studies, our initial series of RARC constituted a select group of patients with lesser tumor burden and fewer comorbidities than those who underwent ORC (6). However, comparison of baseline characteristics of ORC and RARC patients (i.e. comorbidity profile, history of abdominal surgery or pelvic radiotherapy) in our study showed that, as experience in RARC increased, these factors have become less important when discussing the surgical technique. Nonetheless, ORC remains the “go to” approach for patients with large clinically advanced tumors. As such, selections bias must be emphasized and taken into consideration whenever interpreting data in regard to RARC.

The most intriguing finding in our study was the relatively high number of peritoneal carcinomatosis in patients who had undergone RARC. Of patients who had distal recurrences, 9/43 (21%) in the RARC group and 2/26 (8%) in ORC group had peritoneal carcinomatosis. Minimal invasive surgery has been anecdotally linked with seeding of cancer cells to the peritoneum. Several mechanisms have been suggested; the immune effect of CO2 on macrophages located in the peritoneum (7), the attenuated local immune response due to local peritoneal acidosis from CO2 (8), and the mechanical effect of CO2 insulation displacing tumor cells into the peritoneal cavity (9), Whether minimal invasive surgery, in this case RARC, is specifically associated with a risk of intraperitoneal recurrence in bladder cancer has to be further investigated in larger-scale studies. Despite the small number of cases, our findings should be considered an eye-opener, particularly in light of selection bias that favored patients with lesser tumor burden to undergo RARC.

One underappreciated strength of the study is that we provide the rare critical point of view of a surgeon who is a true believer in the value of RARC. In essence, we do not interpret our results as “robot-bashing”. Rather, they are a further step towards understanding the implications of RARC, which may well one day become standard treatment for muscle-invasive bladder cancer. As English author G. K. Chesterton elegantly stated: “What embitters the world is not excess of criticism, but absence of self-criticism. “

References:
1. Nguyen, D.P., et al., Recurrence Patterns After Open and Robot-assisted Radical Cystectomy for Bladder Cancer. Eur Urol, 2015.
2. Volkmer, B.G., et al., Oncological followup after radical cystectomy for bladder cancer-is there any benefit? J Urol, 2009. 181(4): p. 1587-93; discussion 1593.
3. Yafi, F.A., et al., Surveillance guidelines based on recurrence patterns after radical cystectomy for bladder cancer: the Canadian Bladder Cancer Network experience. BJU Int, 2012. 110(9): p. 1317-23.
4. Nepple, K.G., et al., Early oncologic outcomes of robotic vs. open radical cystectomy for urothelial cancer. Urol Oncol, 2013. 31(6): p. 894-8.
5. Tyritzis, S.I., et al., Oncologic, functional, and complications outcomes of robot-assisted radical cystectomy with totally intracorporeal neobladder diversion. Eur Urol, 2013. 64(5): p. 734-41.
6. Kauffman, E.C., et al., Early oncological outcomes for bladder urothelial carcinoma patients treated with robotic-assisted radical cystectomy. BJU Int, 2011. 107(4): p. 628-35.
7. Ost, M.C., et al., Pneumoperitoneum with carbon dioxide inhibits macrophage tumor necrosis factor-alpha secretion: source of transitional-cell carcinoma port-site metastasis, with prophylactic irrigation strategies to decrease laparoscopic oncologic risks. J Endourol, 2008. 22(1): p. 105-12.
8. Hanly, E.J., et al., Abdominal insufflation with CO2 causes peritoneal acidosis independent of systemic pH. J Gastrointest Surg, 2005. 9(9): p. 1245-51; discussion 1251-2.
9. Bouvy, N.D., et al., Impact of gas(less) laparoscopy and laparotomy on peritoneal tumor growth and abdominal wall metastases. Ann Surg, 1996. 224(6): p. 694-700; discussion 700-1.


Written by:
Bashir Al-Hussein, MD and Daniel P. Nguyen, MD
Department of Urology, Bern University Hospital, Bern, Switzerland; Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, NY, USA.

AbstractRecurrence patterns after open and robot-assisted radical cystectomy for bladder cancer

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