Role of surgical approach on lymph node dissection yield and survival in patients with upper tract urothelial carcinoma

doi:10.1016/j.urolonc.2017.09.001

Urologic Oncology: Seminars and Original Investigations

Volume 36, Issue 1, January 2018, Pages 9.e1-9.e9

https://doi.org/10.1016/j.urolonc.2017.09.001 Get rights and content

Highlights

•
Utilization of RNU is increasing over time while ONU decreases and LNU remains stable.
•
RNU does not compromise rates of LND or LN yield compared with ONU.
•
LNU is associated with the lowest rates of LND and LN yield.
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Increasing LN yield in patients with pN0 disease improves OS.
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Surgical approach is not associated with OS in our cohort.

Abstract

Objectives

With increasing utilization of robot-assisted surgery in urologic oncology, robotic nephroureterectomy (RNU) is becoming the surgical modality of choice for patients with upper tract urothelial carcinoma (UTUC). The role of surgical approach on lymph node dissection (LND) and lymph node (LN) yield is unclear, and potential therapeutic effects are unknown. Here we analyze the effects of surgical approach on LN yield, performance of LND, and overall survival (OS).

Methods and materials

Patients with UTUC who underwent nephroureterectomy from 2010 to 2013 were identified in the National Cancer Database. Outcomes of interest included rate of LND, LN yield, and OS. Logistic regression analyses were used to predict performance of LND. Negative binomial regression was used to derive incidence rate ratios for LN yield. Cox proportional hazards models were used to quantify survival outcomes.

Results

A total of 3,116 patients met inclusion criteria. LND was performed in 41% (314/762) of RNU, 27% (380/1385) of LNU cases, and 35% (340/969) of ONU (P<0.001). Compared with an ONU, patients who underwent a LNU had significantly lower odds of receiving a LND (OR = 0.70, 95% CI: 0.55–0.87) and had fewer LNs removed (IRR = 0.69, 95% CI: 0.60–0.80), while RNU trended toward increased LN yield (IRR = 1.14, 95% CI: 0.98–1.33). In a Cox proportional hazards model, increasing LN yield was associated with improved OS in patients with pN0 disease (HR = 0.97 per 1 unit increase in LN yield, 95% CI: 0.95–0.99).

Conclusions

Compared with an ONU, RNU does not compromise performance of a LND and may be associated with improved LN yield. LNU is associated with the lowest rates of LND and LN yield. Increasing LN yield is associated with improved OS in patients with pN0 disease. Despite differential rates of LND and LN yield, surgical approach did not independently affect OS.

Introduction

Upper tract urothelial carcinoma (UTUC) accounts for 5% to 10% of all urothelial carcinomas [1]. The gold standard treatment for high-grade lesions or invasive disease is radical nephroureterectomy with bladder cuff excision. Although routinely performed during radical cystectomy for urothelial carcinoma of the bladder, a formal lymph node dissection (LND) during nephroureterectomy is not a universally agreed upon standard [2]. However, several population-based studies and multi-institutional series have demonstrated that LND and lymph node (LN) yield have diagnostic and therapeutic value [3], especially for muscle-invasive disease. As such there is increasing interest in understanding the role of LND during radical nephroureterectomy.

Minimally invasive approaches are increasingly being utilized to perform complex oncologic procedures that were traditionally performed using an open approach, such as open nephroureterectomy (ONU). Presently, the most commonly performed approach for the surgical management of UTUC is a laparoscopic nephroureterectomy (LNU). However, several studies have demonstrated increasing utilization of robotic nephroureterectomy (RNU) [4], [5]. An associated finding has been the observation of higher rates of LND when a robotic approach to nephroureterectomy is employed [4], [5]. LN yield achieved with RNU, and the attendant effects on oncologic and survival outcomes, however, have not been investigated.

In this study, we examine the relationship between surgical approach and LN yield during nephroureterectomy. We also compare rates of performance of LND between surgical approaches and identify independent predictors of LND. Finally, we evaluate whether LND, LN yield, and approach to nephroureterectomy impact overall survival (OS).

Section snippets

Data source

The National Cancer Database (NCDB) is a hospital registry-based database compiled from more than 1,500 Commission on Cancer accredited centers, and is sponsored jointly by the American College of Surgeons and the American Cancer Society. The NCDB captures more than 70% of newly diagnosed cancers in the United States and represents more than 34 million historical records [6].

Study population

To identify patients with UTUC we first isolated patients with renal pelvis and/or ureteral tumors (ICD-O primary site

Results

A total of 3,116 patients met our inclusion criteria. Clinical covariates stratified by surgical approach are presented in Table 1. Significant differences in sex, income, education level, US region, facility type, tumor-specific characteristics (primary site, laterality, tumor size, tumor grade, and clinical node status), pathologic characteristics (pT stage, pN stage, and surgical margins), and treatment characteristics (performance of a LND, systemic therapy, and treatment year) were found

Discussion

Current literature on the role of LND in the management of UTUC is evolving yet remains controversial. A formal LND for UTUC improves staging, guides the need for adjuvant treatment, and can potentially control micrometastatic disease [3]. A recent meta-analysis found that LND improved cancer-specific survival in patients with muscle-invasive UTUC compared with patients who did not undergo a LND [7]. Although no randomized data exist currently, a prospective study of 90 patients found that LND

Conclusions

RNU does not compromise rates of LND or LN yield compared with an ONU. LNU is associated with the lowest rates of LND and LN yield. When controlling for other variables, increasing LN yield was associated with improved OS in patients with pN0 disease. Despite varying rates of LND and higher LN yield, surgical approach was not associated with OS in our models. Based on this data and others, LND may be considered for patients likely to have pathologically negative LNs at the time of

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Cited by (37)

EDITORIAL COMMENT
2023, Urology
Perioperative and Oncologic Outcomes Associated with Simultaneous Radical Cystectomy and Nephroureterectomy
2023, Urology
Citation Excerpt :
Additionally, 5 of 32 (16%) patients who did not undergo RPLND at the time of nephroureterectomy subsequently developed retroperitoneal nodal recurrence. Recent studies demonstrate that RPLND in patients undergoing nephroureterectomy for UTUC improves CSS, reduces risk of local recurrence, and improves survival even in clinically and pathologically node-negative disease.26-28 Based on these findings, the current EAU guidelines recommend template-based retroperitoneal node dissection for all patients undergoing nephroureterectomy for UTUC, and this should be considered in patients meeting criteria for RCNU.29
To compare the perioperative and oncologic outcomes associated with RCNU to a matched cohort undergoing RC alone. Simultaneous radical cystectomy and nephroureterectomy (RCNU) for synchronous upper tract and bladder urothelial carcinoma is an uncommon procedure. Sparse literature exists comparing outcomes in patients treated with radical cystectomy (RC) alone versus RCNU.
Adults treated with RCNU for urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC) between 1980 and 2020 were identified. Patients were matched 2:1 to patients undergoing RC alone for UCB based on age (+/- 5 years), gender, BMI (+/- 5), Charlson Comorbidity Index, pathologic staging (stage ≤pT2 vs >pT2), and receipt of neoadjuvant chemotherapy. Outcomes included overall survival (OS), recurrence free survival (RFS), cancer specific survival (CSS), 30-day complications, length of stay (LOS), operative time, and estimated blood loss (EBL).
A total of 39 patients undergoing RCNU were identified and matched to 74 patients undergoing RC. There were no significant differences in LOS, EBL, or 30-day complication rates. Operative time was significantly longer in the RC cohort. OS (HR 0.58, CI 0.35-0.97, P = .036) was significantly better for patients undergoing RC alone, while no significant difference was noted in RFS (HR 0.65, 0.34-1.24) and CSS (HR 0.58, CI 0.31-1.08, P = .08).
Patients undergoing RCNU had significantly lower OS compared to a matched group of patients undergoing RC alone. Perioperative outcomes between the groups did not differ significantly. This data can inform patient counseling for treatment of this rare disease state.
Benefit of lymph node dissection in cN+ patients in the treatment of upper tract urothelial carcinoma: Analysis of NCDB registry
2022, Urologic Oncology: Seminars and Original Investigations
The benefits of lymph node dissection (LND) in surgically treated upper tract urothelial carcinoma (UTUC) patients who present with clinically positive nodes at diagnosis remain unclear. The aim of this study was to assess survival differences in cN+ patients who underwent radical nephroureterectomy (RNU) with LND vs. without LND.
The National Cancer Database was used to identify a total number of 423 cN+ patients from 2004 to 2016 with UTUC that underwent RNU. Of the 423 patients, 310 received LND. Kaplan-Meier (KM) plots were used to estimate survival in cN+ patients who received RNU with LND vs. without. Cox proportional hazards regression tested the impact of LND status on overall survival (OS) after adjusting for all available covariates.
Median age of the patient population was 68 years (IQR 61–76), and 56.74% were male. Median follow-up was 1.8 years (IQR 0.9–3.5). For the entire cohort, the 2-year OS rate was 51.8%, and it was 52.1% vs. 51.1% in patients who underwent LND vs. not (log-rank p-value=0.2). On multivariable analysis, performing LND had no statistically significant impact on OS (HR 0.93 95%CI 0.696–1.235, P = 0.9). Repeating the analysis in patients who had exclusively cN1 (HR 0.76 95%CI 0.469–1.223, P = 0.26) or cN2/3 (HR 0.844 95%CI 0.556–1.28, P = 0.43) disease also failed to demonstrate a significant impact of LND on survival.
In cN+ patients with UTUC, performing LND in addition to RNU at any clinical stage does not seem to have a significant impact on OS.
Novel nomograms to predict muscle invasion and lymph node metastasis in upper tract urothelial carcinoma
2022, Urologic Oncology: Seminars and Original Investigations
Citation Excerpt :
An accurate preoperative decision-making tool to help risk stratify patients and predict muscle-invasive disease would be of benefit in guiding clinicians, particularly as more data emerges assessing the efficacy of NAC in UTUC. Despite current European Association of Urology guidelines recommending a template-based LND in patients with presumed muscle-invasive UTUC [14], LND remains underperformed, with retrospective series showing LND being performed in only around 25% to 40% of eligible patients [13,15–16]. This is significant, as LND in UTUC has been shown to improve pathologic staging, and template-based LND has been shown to improve cancer specific survival in patients with muscle-invasive disease and reduce the risk of local recurrence [11–13].
To develop accurate preoperative nomograms for prediction of muscle-invasive disease and lymph node metastasis in upper tract urothelial carcinoma (UTUC), to assist surgeons in risk stratifying patients and help guide treatment decisions.
The National Cancer Database was used to identify all patients from 2004 to 2016 with UTUC who underwent extirpative surgery and lymphadenectomy. Univariate and multivariate logistic regression was performed to identify variables predicting muscle-invasive and node-positive disease. The data set was split 80:20 into a derivation and validation cohort and used to generate and test two nomograms. Nomograms were assessed using area under the curve (AUC) and calibration plots.
A total of 6,143 patients met inclusion criteria. Predictors of muscle-invasive disease were age, grade, lymphovascular invasion (LVI), tumor size, and positive clinical lymph node status. Predictors of node-positive disease were grade, LVI, tumor size, and positive clinical lymph node status. The accuracy of the final nomogram predicting muscle-invasive disease was 80.0% (AUC 0.800, corrected C-index 0.813), and the accuracy of the nomogram predicting node-positive disease was 87.8% (AUC 0.878, corrected C-index 0.887).
With data readily available after imaging and biopsy (age, tumor grade, LVI status, tumor size, and clinical lymph node status), we developed the first preoperative nomograms to quantitatively predict muscle-invasive disease and lymph node metastasis in UTUC, with an accuracy of 80.0% and 87.8% respectively. This information could be helpful to assist surgeons with pre-operative risk stratification.
Robot-assisted versus open radical nephroureterectomy for urothelial carcinoma of the upper urinary tract: A retrospective cohort study across ten years
2021, Surgical Oncology
Citation Excerpt :
In the multivariate analysis, a radical cystectomy prior to surgery was associated with a 2.7 times higher risk of death from any cause. Lenis et al. also found tumor location, size, positive surgical margins, pT and pN stage to be associated with the OS; and patient age and lymph node yield according to Clements et al. [18,35]. As for the PFS, lymph node metastases had the strongest impact with a hazard ratio of 3.3 for metastasized tumors, but also patient age and prior cystectomy.
Radical nephroureterectomy is the gold standard of treatment for high-risk non-metastatic urothelial carcinoma of the upper urinary tract. However, the optimal surgical approach remains a controversial debate. This study compared the perioperative and oncological outcomes of open and robot-assisted radical nephroureterectomies.
131 consecutive radical nephroureterectomies (66 robot-assisted nephroureterectomies vs. 65 open nephroureterectomies) for urothelial carcinoma of the upper urinary tract at a single tertiary referral center were included from 2009 to 2019. The perioperative and oncological outcomes were compared between both surgical approaches, including logistic regression analysis, propensity score matching, Kaplan Meier analyses, and Cox regression models.
Overall, robot-assisted surgery had less blood loss (150 ml vs. 250, p = 0.004) and less positive surgical margins (1.5% vs. 15.4%, p = 0.004) at a comparable operating time (robotic 188min vs. 178). Any grade complications were more frequent after open surgery (40.9% vs. 63.1%, p = 0.011), and the length of stay was shorter after robotic nephroureterectomy (9 days vs. 12, p < 0.001). These differences remained significant in the propensity score matched analysis, except for the complication rates, which were still lower for the robotic approach, but no longer significant. At a median follow-up of 30.9 months (range 1.4–129.5), neither the progression-free survival (PFS, 2-year: robotic 66.7% vs. open 55.3%), nor the overall survival differed significantly (OS, 2-year: robotic 76.2% vs. open 68.4%). In the Cox regression, the surgical approach did not impact the PFS or OS. Lymph node metastases (HR 3.32, p = 0.008) had the strongest impact on the PFS besides patient age (HR 1.51 per 10 years, p = 0.025) and prior cystectomy (HR 2.42, p = 0.026) in the multivariate analysis.
Robot-assisted radical nephroureterectomy had significant perioperative advantages at comparable oncological outcomes compared to open surgery for the treatment of urothelial carcinoma of the upper urinary tract at a high volume center, experienced in robotic surgery.
The role of neoadjuvant chemotherapy, lymph node dissection, and treatment delay in patients with muscle-invasive bladder cancer undergoing partial cystectomy
2021, Urologic Oncology: Seminars and Original Investigations
Citation Excerpt :
NAC was defined as receipt of multiagent chemotherapy before surgery, determined by a variable defining the sequence of treatment events (“Systemic/Surgery Sequence”). Patients were considered to have undergone LND only if the intent to perform this procedure was coded (variable “Scope of LN Surgery”) and if >0 lymph nodes were reported, as previously described [9]. Lymph node yield was used as a surrogate for adequacy rather than extent of template (information not available in NCDB) based on prior literature demonstrating 10 lymph nodes as an appropriate cutoff [10].
To investigate treatment patterns of partial cystectomy (PC), neoadjuvant chemotherapy (NAC), lymph node dissection (LND), and treatment delays, and the associations with overall survival (OS) among patients with muscle-invasive bladder cancer.
We identified patients with cT2–4cN0cM0 urothelial carcinoma of the bladder in the National Cancer Database who underwent PC from 2007 through 2015. We performed descriptive statistics and assessed temporal trends using the Cochrane-Armitage test. Our outcomes of interest were NAC, LND, and treatment delay defined as ≥8 or ≥12 weeks for patients who underwent NAC or upfront surgery, respectively. We used logistic regression and multivariable Cox proportional hazards models to evaluate predictors and associations with OS, respectively.
A total of 9,199 patients met inclusion criteria. Over the study period, PC utilization decreased from 9% to 7% (P = 0.06). Compared with patients who underwent radical cystectomy, patients treated with PC less frequently received NAC (7% vs. 17%, P < 0.01) and LND (57% vs. 91%, P < 0.01), but were less likely to experience treatment delays (25% vs. 31%, P < 0.01). Only 4.1% (27/655) of patients treated with PC received the combination of NAC, LND, and no treatment delay. In a Cox model, adequacy of LND was associated with improved OS (<10 nodes: HR 0.62, 95% CI 0.48–0.81 and ≥10 nodes: HR 0.48, 95% Cl 0.32–0.72).
PC is uncommon and associated with poorer utilization of NAC and LND, but fewer treatment delays. The adequacy of LND was associated with improved OS while NAC and treatment delay were not.

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: Funding: This work was supported by the National Institutes of Health Loan Repayment Program (L30 CA154326 [Principal Investigator: K.C.]), the STOP Cancer Foundation (Principal Investigator: K.C.), and the H & H Lee Surgical Resident Research Award (Recipient: A.T.L.).

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Original articleRole of surgical approach on lymph node dissection yield and survival in patients with upper tract urothelial carcinoma

Highlights

Abstract

Objectives

Methods and materials

Results

Conclusions

Introduction

Section snippets

Data source

Study population

Results

Discussion

Conclusions

Urol Oncol

Eur Urol

J Urol

J Urol

Cancer statistics, 2016

CA Cancer J Clin

The role of lymphadenectomy for upper tract urothelial carcinoma

Nat Rev Urol

Contemporary role of lymph node dissection at the time of radical nephroureterectomy for upper tract urothelial carcinoma

World J Urol

Original article
Role of surgical approach on lymph node dissection yield and survival in patients with upper tract urothelial carcinoma