It is widely accepted by urologists that a pelvic lymph node (LN) dissection (LND) is an integral part of the surgical management of muscle-invasive urothelial carcinoma (UC) of the bladder.¹ However, despite the pathological similarities between invasive UC of the bladder and upper-tract UC (UTUC), no such guideline-based consensus exists regarding the utilization of LND at the time of radical nephroureterectomy (RNU) for UTUC. The reasons for this are multifaceted and include low-quality evidence, variable lymphatic metastatic landing zones based on tumor location and challenges in risk-stratifying UTUC patients prior to surgical intervention. The lack of accepted dissection templates and resultant lack of consistency in the literature make comparisons across studies difficult. Furthermore, clinicians do not agree on metastatic landing zones based on anatomical tumor location, with significant ongoing controversy surrounding the concept of cranial migration of mid to distal ureteral tumors and the impact on dissection templates.² Taken in the context of a relatively rare malignancy, compiling high-quality data that guides management has proven challenging.

Despite being validated in the literature as both feasible and safe, performance of LND at the time of RNU appears infrequent. A Canadian population-based study demonstrated that only 27% of RNU surgical specimens included LNs.³ The lack of adoption speaks to the inconsistent evidence base that is generally limited to single-institution series, which again lack strict inclusion parameters and LND templates. In response to the lack of high-quality evidence, the Upper Tract Urothelial Collaborative was developed, which has improved the available literature to include multi-institutional series evaluating the role of LND for UTUC.^4,5 However, even these studies continue to be limited by heterogeneity in the patient population and a lack of templated LNDs.

The potential value of LND for UTUC at the time of RNU can be viewed from the perspective of staging/prognostics and/or from a therapeutic perspective. In the case of the former, there is a body of evidence to support a staging benefit from LND at the time of RNU. Larger multi-institutional and population-based studies have demonstrated that patients with pathological LN metastasis (pN+) have a worse prognosis with lower cancer-specific survival (CSS) compared to patients with no LN metastasis (pN0) or unknown status (pNx).^4,6 This is important information when determining which patients to triage into more aggressive adjuvant treatment pathways following RNU. The available literature also indicates that patients with no organ-confined disease likely benefit the most from LND.^4,7 Despite these studies, in the absence of prospective trials with rigorous inclusion criteria and strict dissection templates, conclusions cannot be definitively drawn. It should be acknowledged that some studies do attempt to define dissection templates, but most are retrospective and multi-surgeon series, calling into question how strictly those templates could be adhered to.

The therapeutic benefits of LND for UTUC, or lack thereof, are considerably less established and remain a controversial topic among clinicians. There is evidence across several studies that a CSS benefit can be derived from performing an LND at the time of RNU compared to no LND.^4,8 Some authors have even demonstrated an overall survival benefit in patients undergoing LND in small retrospective series.⁹ Roscigno et al, in a large multi-institutional study, found CSS to be significantly longer in pN0 patients compared to pNx (73% vs 48%, p <0.0001).⁸ It must be noted, however, that no difference in CSS was observed between pN0 and pNx cohorts. However, a large multi-institutional analysis did find that a difference in CSS between pN0 and pNx cohorts existed, although this benefit was only true for patients with ≥pT2 disease.⁴ Once again, the evidence suggests that more locally advanced/nonorgan-confined disease may benefit the most from LND at the time of RNU. Conversely, another large multi-institutional cohort analyzed by Lughezzani et al demonstrated no evidence that LND has a therapeutic benefit.¹⁰ Still, in the absence of established dissection templates, this body of literature remains heterogeneous in its inclusion criteria and thereby heterogeneous in its conclusions.

Figure 1. LND templates for both renal pelvis and proximal ureteral tumors as described by Matin et al.² The red boxes with solid black lines and corresponding percentages reflect percentage of LN metastases that would be detected if the dissection were carried out using this template. The dashed line boxes represent the additional yield when the dissection is extended to include these areas.

Figure 2. LND templates for mid ureteral (A and B) and distal ureteral (C and D) tumors as described by Matin et al.² The red boxes with solid black lines and corresponding percentages reflect percentage of LN metastases that would be detected if the dissection were carried out using this template. The dashed line boxes represent the additional yield when the dissection is extended to include these areas.

A pervasive theme in the evaluation of this literature is the lack of predefined dissection templates, which limits standardization of surgical approach and interpretation of studies against one another. Several authors have published works to refine our understanding of metastatic landing zones in UTUC. Most recently, Matin et al confirmed understood migration patterns for proximal tumors (renal pelvis and proximal ureteral tumors; Fig. 1) while expanding our understanding of migration patterns in mid to distal ureteral tumors.² Notably, this study revealed that cranial migration of LN metastasis can be observed in mid ureteral (62.5%–100%) and distal ureteral (16%–25%) tumors (Fig. 2). The cranial migration phenomenon appears to be stepwise, however, which suggests that intraoperative frozen section may ultimately define the extent of the dissection.

In order to establish guidelines surrounding LND at the time of RNU, it is paramount that randomized controlled trials be conducted utilizing predetermined dissection templates and strict inclusion criteria. Until we can expand this knowledge base, however, the available evidence suggests consideration of template-based LND at the time of RNU to gain prognostic information that guides adjuvant care pathways and possibly improves oncologic outcomes, especially for patients with nonorgan-confined disease.