The prognostic impact of lymph node dissection for clinically node-negative upper urinary tract urothelial carcinoma in patients who are treated with radical nephroureterectomy

Abstract

Background To evaluate the prognostic impact of lymph node dissection (LND) in patients who underwent radical nephroureterectomy (RNU) with bladder cuff excision (BCE) for clinically node-negative (cN0) upper urinary tract urothelial carcinoma (UTUC). Methods We retrospectively enrolled 520 patients with cN0 UTUC in a single tertiary referral center from 2000 to 2015. The patients were divided into three groups: patients with and without pathologically proved lymph node metastasis (pN1–3 and pN0, respectively) and patients without LND (pNx). We analyzed associations between overall survival (OS)/ disease-free survival (DFS)/ cancer-specific survival (CSS) and clinical characteristics. Results The patients were divided into three groups (pN1–3, pN0 and pNx with 20, 303, and 197 patients, respectively). OS/DFS/CSS in the pN1–3 group were significantly worse (all p<0.001) compared with the pN0 group. However, there were no significant differences between the pNx and pN0 groups. In the multivariate analyses, CSS was only affected by age [(hazard ratio (HR) = 1.03, p = 0.008]), positive surgical margin (HR = 3.38, p<0.001) and pathological T3–4 stages (HR = 4.07, p<0.001). In the subgroup analyses for patients with LND, locally advanced disease (pT3 and pT4) had significantly more metastases [T3–4: 13.91% (16/115) vs. T0–2: 1.92% (4/208), p<0.001]. Conclusions In the pN0 group, LND for cN0 UTUC did not show therapeutic benefits in terms of DFS, CSS, and OS. However, LND with RNU allowed optimal tumor staging, through patients still had a poor prognosis. Clinically occult LN metastases were found in 6.2% of our patients.

The Association between Lymph Node Dissection and Survival in Lymph Node-Negative Upper Urinary Tract Urothelial Cancer

“…On the other hand, some retrospective studies showed that there was no survival difference between cN0 patients who did and did not undergo LND, but the subgroup analyses according to the number of removed LNs were not performed [ 19 , 20 ]. One of the multicenter retrospective analyses demonstrated that in cN0 muscle-invasive UTUC (≥pT2 stage) LND did not provide a survival benefit when compared to no LND [ 20 ].…”

Need for and extent of lymph node dissection for upper tract urothelial carcinoma: an updated review in 2023

“…Theoretically, the pNx cohort includes both pN0 and pN+ patients if they had undergone LND; therefore, when compared with pN0 patients, worse oncologic outcomes in pNx patients (no LND) would be expected. On the contrary, Burger et al , Li et al , Hsieh et al , Lughezzani et al , Chappidi et al , and Lenis et al showed no differences in DFS, CSS, and OS between patients with pNx and pN0, suggesting that survival outcomes are affected by patient selection, as patients harboring advanced disease associated with potential lymph node metastasis being more likely to undergo LND [28,31,32,35,37,38].…”

“…The authors showed inferior DFS (hazard ratio 2.40, P < 0.001) and CSS (hazard ratio 2.39, P < 0.001) in pN+ patients compared with pN0 patients using multivariable Cox regression analysis [27]. As shown in Table 1, compared with pN0, the negative prognostic impact of pN+ with regard to DFS and CSS has been supported by several studies, such as Burger et al [28] in 2011 (hazard ratio for DFS: 2.0, hazard ratio for CSS: 2.1, n = 785), Mason et al [29] in 2012 (hazard ratio for DFS: 2.01, hazard ratio for CSS: 2.94, n = 1029), Ikeda et al in 2017 (hazard ratio for DFS: 3.25, hazard ratio for CSS: 3.56, n = 399) [30], Li et al in 2021 (hazard ratio for CSS: 3.08, hazard ratio for CSS: 4.41, n = 1340) [31], Hsieh et al [33] in 2022 (hazard ratio for CSS: 2.01, n = 520) [32], Lee et al [34 ▪▪ ] in 2022 ( P < 0.001 in DFS and P = 0.01 in CSS, n = 658), and Hakimi et al in 2022 (HR for DFS: 1.80, HR for CSS: 2.74, n = 877). In addition, two studies showed that pN+ was associated with worse OS in UTUC patients compared to pN0; for example, Mason et al in 2012 (HR for OS: 2.70, n = 1029) and Hakimi et al in 2022 (hazard ratio for OS: 2.77, n = 877) [29,31].…”

“…Several retrospective studies have assessed the potential impact of LND on oncologic outcomes, comparing patients who underwent LND (pN0 and/or pNþ) with those who did not (pNx). When comparing oncologic outcomes of pN0 with pNx patients, data from retrospective studies are contradictory, with half of them showing worse oncologic outcomes for pNx patients and the other half not [27][28][29][30][31][32]. For example, Roscigno et al [27] and Ikeda et al [30] reported that, compared with pN0 patients, pNx patients had worse DFS and CSS (Table .1).…”

“…Theoretically, the pNx cohort includes both pN0 and pNþ patients if they had undergone LND; therefore, when compared with pN0 patients, worse oncologic outcomes in pNx patients (no LND) would be expected. by patient selection, as patients harboring advanced disease associated with potential lymph node metastasis being more likely to undergo LND [28,31,32,35,37,38]. Zhai et al [39] assessed the impact of performing LND during RNU on CSS and OS using 7278 patients from the SEER database.…”