2.1

Patient cohort

From our prospectively-maintained institutional bladder cancer database, we extracted and retrospectively analyzed all patients who underwent RC with bilateral standard PLND – as per institutional protocol – between 2014 and 2023.

Only patients with available data regarding tumor location at TURBT, and lymph-nodal status at final pathology report s/p RC were included in the analysis.

Patients who were clinically node-positive and/or who had metastatic disease at preoperative staging were excluded. Also, patients who underwent neoadjuvant chemotherapy were excluded from the analysis.

Specifically for the purpose of the study, tumor endoluminal location at the last TURBT performed was defined as:

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  right-sided, which included disease involving the right bladder wall and/or the right trigone;

  
  
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  median-line, including disease of the central trigone, the posterior wall, the dome and/or the anterior wall;

  
  
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  left-sided, with disease involving the left bladder wall and/or the left trigone;

  
  
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  diffuse, multi-focal disease.

2.2

Lymph node dissection

Lymph node dissection was carried out according to the standard template cited in the introduction. While in some cases, pelvic lymph nodes were excised en-bloc (n=43), in the majority of the patients (n=196), they were individually grouped following a standardized anatomical template, comprising external iliac, internal iliac plus obturator, presacral, Marcille’s common iliac, and Cloquet’s nodal stations bilaterally. Specimens were immersed in formalin, enumerated, and then examined for cancer infiltration, with staging assigned in accordance with the 2017 version of the TNM system (8th edition).

2.3

Outcome

The primary outcome was to assess whether tumor endoluminal location at TURBT was predictive of ipsilateral pelvic lymph-nodal involvement.

2.4

Covariates

Relevant demographic and tumor-related data were considered to account for the potential effect of confounders. Demographic data included patient age (at the time of surgery), gender, ASA score, and Charlson’s comorbidity index. Tumor-related characteristics included endoscopic tumor size (in mm), pT stage, 2016 WHO Grading, histological subtype at TURBT and RC, and number of nodes excised during PLND. The year of surgery was also collected.

2.5

Statistical analysis

Descriptive statistics were used to characterize the study cohort, stratified by tumor location; frequencies and proportions were used for categorical data, while medians, interquartile ranges (IQR), and 5°–95° centiles were used for continuous data. Kruskal-Wallis and chi-square tests were used to compare the statistical significance of differences in the distribution of continuous and categorical variables, respectively, between different endoluminal tumor locations. Distribution in the percentage of ipsilateral positive lymph-nodes and in the number of ipsilateral positive lymph-nodes between different tumor locations was assessed with Kruskal-Wallis. Linear regressions were fitted to assess whether the left or right location, compared to the rest of the locations grouped, was associated with an increased number of ipsilateral positive lymph-nodes and an increased percentage of ipsilateral positive lymph-nodes out of the total number of nodes excised; Beta coefficients and 95%C.I. have been reported.

All statistical tests were performed using SPSS IBM SPSS Statistics version 23.0 (Armonk, NY: IBM Corp.). All tests were two-sided with a significance level set at P < 0.05.