Oncologic Outcomes for Open and Laparoscopic Radical Nephroureterectomy in Patients with Upper Tract Urothelial Carcinoma – Beyond the Abstract

Laparoscopic radical nephroureterectomy (LNU) has become popular as a minimally-invasive surgical alternative. Several studies have compared the oncologic outcomes between open radical nephroureterectomy (ONU) and LNU in patients with upper tract urothelial carcinoma (UTUC) and have demonstrated comparative outcomes between these. However, other studies have shown an increased risk of recurrence with LNU. Due to limitations of the heterogeneity of study population, sample size, and surgical techniques, the oncologic efficacy of LNU to ONU has remained undetermined. In addition, several guidelines have recommended laparoscopic procedures for localized (stage cT2 or less) disease, but their use remains unclear for locally-advanced (stages cT3-4 and/or cN+) disease. In this study, we retrospectively compared the oncologic outcomes between ONU (n = 181) and LNU (n = 48) in a multi-institutional cohort of patients with locally-advanced UTUC using inverse probability of treatment weighting (IPTW)–adjusted Cox regression analyses. 

We observed significant differences in patient backgrounds, including preoperative renal function, lymph node involvement, lymphovascular invasion, and surgical margins, between the groups. Before the background adjustment, intravesical recurrence-free survival (RFS), visceral RFS, cancer-specific survival (CSS), and overall survival (OS) were significantly inferior in the ONU group than in the LNU group. However, in the IPTW–adjusted Cox regression analysis, no significant differences were observed in intravesical RFS (hazard ratio [HR], 0.65; P = 0.476), visceral RFS (HR, 0.46; P = 0.109), CSS (HR, 0.48; P = 0.233), and OS (HR, 0.40; P = 0.147). In addition, background-adjusted IPTW analyses for all patients (n = 426) demonstrated that the laparoscopic approach was not a significant factor for intravesical RFS, visceral RFS, CSS and OS. These results suggest that the impact of the laparoscopic approach was not independently associated with prognosis, but there might be a trend toward an association between the laparoscopic approach and prolonged OS. 

Previous studies support our finding for oncologic benefits of LNU. In a meta-analysis of 21 observational studies of patients with UTUC who underwent ONU or LNU, LNU was reported to provide not different prognostic effects for UTUC and was associated with a better oncologic control of extravesical RFS and CSS than ONU 1. The investigators reported pooled HRs of 1.05 (95% CI, 0.92–1.18; P = 0.134) for intravesical RFS between the LNU (n = 1959) and ONU (n = 4281) groups, 0.80 (95% CI, 0.64–0.96; P = 0.859) for extravesical RFS (n = 836 and 4315, respectively), 0.79 (95% CI, 0.68–0.91; P = 0.186) for CSS (n = 2518 and 8342, respectively), and 0.91 (95% CI, 0.66–1.17; P = 0.091) for OS (n = 1442 and 3119, respectively). A recent study from the Multi-Institutional National Database of the Japanese Urological Association including 749 patients with stage pT2≥cNxM0 disease who underwent LNU (n = 222) or ONU (n = 527) has suggested no significant differences between the two groups in RFS, CSS, and OS. In addition, OS was not significantly different between the two groups even when the patients were stratified by stage pT3/pT4 and/or pN+ disease (P = 0.2876). They concluded that there is no evidence that oncologic outcomes of LNU are inferior to those of ONU in muscle-invasive UTUC when appropriate patients are selected 2

In contrast, a multicenter analysis of 849 patients with UTUC who underwent LNU (n = 446, 53%) or ONU (n = 403, 47%) at the Canadian Upper Tract Collaboration demonstrated that the surgical approach is not independently associated with OS (HR, 0.89; 95% CI, 0.63–1.27; P = 0.52) and disease-specific survival (HR, 0.90; 95% CI, 0.60–1.37; P = 0.64), but there is a trend toward an independent association between LNU and poor RFS (HR, 1.24; 95% CI, 0.98–1.57, P = 0.08) 3. A single center study from Seoul National University has suggested that LNU is independently associated with worse 5-year CSS (66.1% vs. 80.2%; P = 0.015) and OS (59.1% vs. 75.2%; P = 0.027) rates than those of ONU [10]. Multivariate analyses have shown that LNU is significantly associated with poor CSS (HR, 2.50; P = 0.005) and OS (HR, 2.59; P = 0.001) in patients with stage pT3/pT4 disease 4. However, considering these studies with the intrinsic bias of retrospective study design, the results should be interpreted with caution. In the first randomized prospective study, progression-free survival and CSS were superior in the ONU group (n = 9) than in the LNU group (n = 7) among patients with stage pT3 tumors, whereas prognosis in all patients (n = 80) was not significantly different between the groups (n = 40 and 40, respectively) 5. However, the number of patients in the stage pT3 subgroup was too small to conclude the impact of LNU on prognosis, even if it was conducted as a randomized prospective study. Taken together, as large multicenter studies 1-3,5-9 and our results suggest, LNU could provide not different prognostic effects for UTUC as does ONU.

Several limitations of the present study must be acknowledged. First, the use of data from multiple centers and the retrospective study design prevented us from making definitive conclusions regarding the impact of LNU on prognosis. We could not address median numbers of the resected LNs in each approach due to the lack of data, and the differences in surgical procedures including approaches (transperitoneal or retroperitoneal) and positions (supine or lateral position). Despite the use of an IPTW method, which is an attractive method for estimating treatment effects using observational data, we were unable to control for selection bias and other unmeasurable confounders of retrospective studies. Despite these limitations, we evaluated the direct impact of LNU on oncologic outcomes in patients with UTUC using IPTW–adjusted Cox regression analyses. Because only a single prospective study was available to compare the influence of surgical approach on prognosis, our results support the rationale that the laparoscopic approach provides a not different value on the prognosis for locally-advanced UTUC. In conclusion, surgical approaches were not independently associated with prognosis in patients with locally-advanced UTUC.

Written by: Shingo Hatakeyama, MD. Ph.D. Assistant Professor, Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

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1 Zhang, S., Luo, Y., Wang, C., Fu, S. J. & Yang, L. Long-term oncologic outcomes of laparoscopic nephroureterectomy versus open nephroureterectomy for upper tract urothelial carcinoma: a systematic review and meta-analysis. PeerJ 4, e2063, doi:10.7717/peerj.2063 (2016).

2 Miyazaki, J. et al. Laparoscopic Versus Open Nephroureterectomy in Muscle-Invasive Upper Tract Urothelial Carcinoma: Subanalysis of the Multi-Institutional National Database of the Japanese Urological Association. J Endourol 30, 520-525, doi:10.1089/end.2015.0757 (2016).

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