Purpose: We assessed the prognostic value of extranodal extension and other lymph node parameters in a large multicenter cohort of patients with lymph node metastasis after radical nephroureterectomy. Materials and Methods: We retrospectively analyzed the records of 222 patients with lymph node metastasis treated with radical nephroureterectomy for upper tract urothelial carcinoma without neoadjuvant therapy. Each lymph node metastasis was microscopically evaluated for extranodal extension. Results: A median of 4 lymph nodes (IQR 8) was removed. Two lymph nodes (IQR 2) were positive. Lymph node density was 51.3% (IQR 71.7%). Overall 110 patients (49.5%) had extranodal extension, which was associated with more advanced pT stage (p = 0.026). On multivariable analysis extranodal extension was associated with disease recurrence (p = 0.01) and cancer specific mortality (p = 0.013). When stratified by a 30% cutoff, lymph node density was associated with disease recurrence and cancer specific mortality on univariable but not multivariable analysis (p = 0.048 and 0.049, respectively). Adding extranodal extension to a multivariable model including pT stage and tumor architecture improved predictive accuracy for disease recurrence from 70.3% to 74.5% (p <0.001). Adding extranodal extension to a multivariable model including age, pT stage and tumor architecture improved predictive accuracy for cancer specific mortality from 70.6% to 74.4% (p <0.001). Conclusions: Extranodal extension is a powerful predictor of clinical outcomes in patients with upper tract urothelial carcinoma with lymph node metastasis. While other lymph node parameters seem to have limited clinical value, extranodal extension could help risk stratify patients with upper tract urothelial carcinoma and lymph node metastasis for better counseling and clinical trial design.
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