Robot-Assisted Radical Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma: A Promising Alternative to Open Surgery or a Future "Gold Standard"?

Upper urinary tract urothelial carcinomas (UUT-UCs) are uncommon malignancies (1 to 4 new cases per 100,000 persons per year) and account for only 5% to 10% of all urothelial neoplasms.1 Unlike bladder cancer, about 60% of UUT-UCs are invasive at the time of diagnosis2 and therefore require a radical surgical treatment in most cases. Open radical nephroureterectomy (ONU) with bladder cuff excision is still the gold standard treatment for UUT-UC, regardless of the tumor location in the upper urinary tract.2 Laparoscopic radical nephroureterectomy (LNU), first described by Clayman et al in 1991,3 had been proposed as an alternative, minimally invasive option for the surgical management of UUT-UC, offering overlapping oncologic results4 but better perioperative outcomes5 and improved cosmesis when compared to ONU. Survival benefits of radical nephroureterectomy (RNU) have been widely discussed: the Upper Urinary Tract Urothelial Carcinoma Collaboration Group reported, in those patients who underwent either open or laparoscopic radical nephroureterectomy for UUT-UC, overall 5-year recurrence-free survival (RFS) and cancer-specific survival (CSS) rates of 69% and 73%, respectively.6 The avoidance of tumor spillage and seeding into the operative field, the complete excision of the bladder cuff,7 and, perhaps, an accurate retroperitoneal or pelvic lymph node dissection8 and 9 are surgical steps of paramount importance that might be achieved in those patients with life-threatening disease, such as high-grade, high-stage, multifocal UUT-UC. Robotic surgery has been recently developed as the natural evolution and simplification of traditional laparoscopy, being able to bridge the technical difficulties related to the handling of laparoscopic instruments and allowing the performance of even challenging or complex urologic procedures.10 However, robot-assisted laparoscopic radial nephroureterectomy (RAL-NU) is still considered to be in its infancy stage: there are only a few studies with low numbers of patients and short-term follow-up; no randomized clinical trials comparing RAL-NU with other approaches have been published, and long-time survival reports are not yet available.11 In this issue of Clinical Genitourinary Cancer, Lim et al 12 have reported the intermediate-term oncologic results of 32 consecutive patients who underwent RAL-NU (performed by either traditional multiport or laparoendoscopic single-site approach) for clinically localized or locally advanced UUT-UC. Remarkably, this is the largest available study with the longest follow-up duration. The reported survival outcomes at 2 and 5 years sound unequivocally promising: the CSS rates were 87.3% and 75.8%, respectively; moreover, the urothelial RFS rates were 68% (at both 2 and 5 years of follow-up), similar to the nonurothelial rates (71.5% and 68.1% at 2 and 5 years, respectively). Interestingly, these results seem comparable to those observed after ONU: the robotic arms' degrees of freedom, the three-dimensional magnification of the operative field, and the possibility to replicate the open surgery movements, while maintaining the same oncologic safety, could be some possible reasons for such encouraging data. Female gender (P = .02) and pathologic stage pT2 or higher (P = .049) were found to be independent prognostic factors for RFS; conversely, no significant predictors of CSS at both univariate and multivariate analyses were found. 12 Comparable prognosticators have been described in open and laparoscopic RNU series, 13 and 14 in which other factors were also found to be significant predictors of RFS and CSS, including age, pathologic grade, node status, lymphovascular invasion, histologic architecture, smoking history, previous bladder tumors, and concomitant carcinoma in situ, which are similar to those reported for the lower urinary tract urothelial cell carcinomas. 15, 16 and 17 Some authors argued that retroperitoneal lymph node dissection (RPLND) at the time of RNU could provide diagnostic and therapeutic benefits, especially in those patients with high-risk disease, 8 and 9 even if a definitively accepted consensus does not yet exist, in contrast to the widely recognized consensus for invasive bladder cancer. 18 In the paper by Lim et al, 12 RPLND was not performed for any of the 32 cases. As the authors stated, this is an important limitation of the study, even if only 1 patient (3%) experienced para-aortic lymph node recurrence during the follow-up. We believe that robotic assistance would have allowed a meticulous and effective retroperitoneal lymph node dissection in those patients, with a potentially low incidence of intraoperative and postoperative complications. Considering the feasibility and safety of RAL-NU, 11 and the promising oncologic outcomes reported in this paper, 12 robot-assisted laparoscopic radical nephroureterectomy could be an encouraging alternative to open surgery in high-volume centers in which the Da Vinci platform is available. As soon as a higher number of studies with long-term follow-up (or oncologic and perioperative results from clinical trials comparing a robotic approach with ONU) are available, RAL-NU could become a future gold standard for the surgical management of UUT-UC.