Does increasing the nodal yield improve outcomes in patients without nodal metastasis at radical cystectomy?

Purpose: To determine whether the number of lymph nodes (LNs) examined is associated with outcomes in patients without nodal metastasis after radical cystectomy (RC). Patients and Methods: We retrospectively analyzed data from 4,188 patients treated at 12 centers with RC and pelvic lymphadenectomy without neo-adjuvant chemotherapy for urothelial carcinoma of the bladder (UCB). Outcomes of patients without LN metastasis (n = 3,088) were examined according to the LN yield analyzed as continuous variable, tertiles, and using the cutoffs of ≥9 and ≥20. Results: The median nodal yield was 18 (range 1-123; IQR:20). A total of 2591 (84 %) and 1445 (47 %) patients had a LN yield ≥9 and ≥20, respectively. Median follow-up was 47 months (IQR:70). In multivariable analyses that adjusted for the standard clinicopathologic factors, higher LN yield was associated with a decreased risk of disease recurrence (continuous: HR = 0.996, p = 0.05; 3rd vs 1st tertile: HR = 0.853, p = 0.048; cutoff ≥20: HR = 0.851, p = 0.032). In the subgroups of patients with muscle-invasive UCB or those with ≥9 LN removed, LN yield was not associated with outcomes (p values >0.05). Conclusions: In this large multicenter cohort of patients with node-negative UCB, higher nodal yield improved recurrence-free survival when all patients were analyzed. Patients with a high LN yield (≥20 LN removed or 3rd tertile) had the largest benefit. The lack of prognostic significance of LN yield in patients with muscle-invasive UCB or those stratified by 9 LNs removed suggests that this effect is weak. Further prospective studies are needed to help identify preoperatively the optimal template for each patient.