Urologic Oncology: Seminars and Original Investigations
Original articleLymph node yield and tumor location in patients with upper tract urothelial carcinoma undergoing nephroureterectomy affects survival: A U.S. population–based analysis (2004–2012)
Introduction
The standard of care for high-risk upper tract urothelial carcinoma (UTUC) is nephroureterectomy with bladder cuff excision. The decision to perform a routine pelvic or retroperitoneal lymph node dissection (LND) is controversial [1]. A number of studies, including population-based data [2], [3], [4], demonstrate no difference in cancer-specific survival (CSS) with LND [2], [3], [4], [5], [6], [7] and no survival benefit with higher LN counts [8], [9]. However, several studies from centers of excellence report an improvement in CSS with LND and higher node counts being associated with improved survival [10], [11], [12], [13], [14], [15]. Recently, the National Comprehensive Cancer Network changed their guidelines to recommend LND in patients with high-grade UTUC and to consider LND in patients with low-grade disease [16]. However, the extent to which urologists in the United States perform LNDs in patients with UTUC remains unknown.
In addition to the controversy regarding LND, there is disagreement regarding the importance of tumor location (ureteral vs. renal pelvis) as a predictor of CSS [17]. Previous retrospective studies show worse survival with ureteral tumors [18], [19], whereas others report no survival difference based on tumor location [6], [7], [20], [21]. The largest population-based analysis of this topic to date reported worse CSS in renal pelvis tumors, and the authors hypothesized the higher rates of N+disease and more advanced T stage could explain the worse survival in patients with renal pelvis tumors [2]. However, this question has not been addressed in a more contemporary population-based cohort.
This study was designed with 3 aims to investigate these controversial issues in the treatment of UTUC. First, to investigate contemporary trends in the rates of LND at the time of nephroureterectomy for the treatment of UTUC in the United States. Second, to determine if an increased number of nodes removed during LND results in improved CSS. Third, to investigate the role of tumor location and laterality as it relates to the rates of N+disease and CSS.
Section snippets
Patient cohort
With institutional review board approval, we identified individuals in the Surveillance, Epidemiology, and End Results (SEER) database with renal pelvis (ICD-9, 65.9) and ureteral (ICD-9, 66.9) malignancies [2]. Of the 15,222 patients with UTUC, a total of 6,397 patients underwent nephroureterectomy (code 40). Exclusion criteria included nonurothelial histology (urothelial codes 8120–8130), previous malignancies, lack of histologic confirmation of diagnosis, and unknown LND status.
Results
Of the 2,862 individuals in the cohort, 721 (25%) underwent LND and 2,141 (75%) did not undergo LND at the time of nephroureterectomy. Similarly, among 2,079 individuals with grade 3/4 disease, 27% (566/2079) underwent LND at the time of nephroureterectomy.
Discussion
This is the most recent population-based analysis of trends in LND for the treatment of UTUC, building on strong evidence supporting the use of LND in recent years. In the United States, there was a significant increase in LND rates at the time of nephroureterectomy for UTUC from 2004 to 2012 with younger patients and patients with high-grade, left-sided tumors, and large tumors more likely to undergo LND. To our knowledge, this is the first population-based study to show an increased LN count
Conclusions
Rates of LND at the time of nephroureterectomy for UTUC have significantly increased from 2004 to 2012. Moreover, an increase in the number of LNs removed portends a survival advantage for patients in this study irrespective of nodal status. These findings highlight the importance of intentional LNDs with an adequate lymph node yield in patients with UTUC undergoing nephroureterectomy as≥5 LNs were associated with the greatest survival advantage. Additionally, ureteral tumor location is a
References (34)
- et al.
Lymphadenectomy at the time of nephroureterectomy for upper tract urothelial cancer
Eur Urol
(2011) - et al.
Location of the primary tumor is not an independent predictor of cancer specific mortality in patients with upper urinary tract urothelial carcinoma
J Urol
(2009) - et al.
A critical appraisal of the value of lymph node dissection at nephroureterectomy for upper tract urothelial carcinoma
Urology
(2010) - et al.
Gender-related differences in patients with stage I to III upper tract urothelial carcinoma: results from the surveillance, epidemiology, and end results database
Urology
(2010) - et al.
The effect of tumor location on prognosis in patients treated with radical nephroureterectomy at Memorial Sloan-Kettering Cancer Center
Eur Urol
(2010) - et al.
Prognostic value of lymph node dissection in patients with muscle-invasive transitional cell carcinoma of the upper urinary tract
Eur Urol
(2008) - et al.
Impact of the extent of regional lymphadenectomy on the survival of patients with urothelial carcinoma of the upper urinary tract
J Urol
(2007) - et al.
Stage-specific impact of tumor location on oncologic outcomes in patients with upper and lower tract urothelial carcinoma following radical surgery
Eur Urol
(2012) - et al.
Prediction of true nodal status in patients with pathological lymph node negative upper tract urothelial carcinoma at radical nephroureterectomy
J Urol
(2013) - et al.
Prognostic factors in upper urinary tract urothelial carcinomas: a comprehensive review of the current literature
Eur Urol
(2012)
Prognostic significance of bladder tumor history and tumor location in upper tract transitional cell carcinoma
J Urol
The impact of tumor location on prognosis of transitional cell carcinoma of the upper urinary tract
J Urol
Nephroureterectomy and segmental ureterectomy in the treatment of invasive upper tract urothelial carcinoma: a population-based study of 2299 patients
Eur J Cancer
Ability of clinical grade to predict final pathologic stage in upper urinary tract transitional cell carcinoma: implications for therapy
Urology
Primary site and incidence of lymph node metastases in urothelial carcinoma of upper urinary tract
Urology
Lymph node yield at radical cystectomy predicts mortality in node-negative and not node-positive patients
Urology
No overt influence of lymphadenectomy on cancer-specific survival in organ-confined versus locally advanced upper urinary tract urothelial carcinoma undergoing radical nephroureterectomy: a retrospective international, multi-institutional study
World J Urol
Cited by (29)
Pelvic lymphadenectomy: Evaluating nodal stage migration and will rogers effect in bladder cancer
2024, Urologic Oncology: Seminars and Original InvestigationsRadical Nephroureterectomy Tetrafecta: A Proposal Reporting Surgical Strategy Quality at Surgery
2022, European Urology Open ScienceCitation Excerpt :Based on these considerations, and despite the inherent limitation of the unsatisfactory accuracy of preoperative nodal staging, current international guidelines recommend LND in patients with muscle-invasive disease [1]. In our series, LND has been performed following guideline recommendations in 87% of the cases, a proportion significantly higher than that reported in the literature [20]. Nevertheless, as the guidelines also suggest that a template-based LND should be offered to all patients who are scheduled for RNU, an LND was probably performed more often in the tertiary expert centers involved.
Site of metastatic recurrence impacts prognosis in patients with high-grade upper tract urothelial carcinoma
2021, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :Of note, surgical approach is not associated with recurrence after RNU for UTUC, despite recent studies suggesting atypical systemic recurrence patterns following minimally invasive surgeries for urologic cancers [14]. Similarly, while an increase in the number of nodes removed on lymph node dissection has been shown to be associated with improved cancer-specific survival in UTUC [15], lymph node yield does not seem to impact metastatic disease recurrence after RNU in our cohort. LVI is not reported in SEER and was not evaluated in the study by Dong et al. [11].
Oncologic outcomes of laparoscopic radical nephroureterectomy in conjunction with template-based lymph node dissection: An extended follow-up study
2020, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :The role of lymph node dissection (LND) remains controversial in the treatment of patients with nonmetastatic upper urinary tract urothelial carcinoma (UTUC) [1-4]; for example, the EAU guideline states that LND has only a limited recommendation for invasive cases alone [1]. However, recent population-based studies revealed that the percentage of patients receiving lymphadenectomy increased from 20% (60/295) in 2004 to 33% (106/320) in 2012 in the USA [2], suggesting the gradual dissemination of regional LND with radical nephroureterectomy (NU) in real-world clinical practice. So far, focusing on precise pathological disease staging and the potential therapeutic advantage, our group has been routinely performing regional LND in conjunction with laparoscopic NU as well as open NU for patients with clinically node-negative UTUC [3].
Nephroureterectomy with or without Bladder Cuff Excision for Localized Urothelial Carcinoma of the Renal Pelvis
2020, European Urology Focus