A Predictive Nomogram for Development of Lymph Node Metastasis in Muscle-Invasive Bladder Cancer Following Neoadjuvant Therapy

Pelvic lymph node metastases (ypN+) after multiagent neoadjuvant chemotherapy (NAC) is a poor prognostic sign in nonmetastatic muscle-invasive bladder cancer (nmMIBC). We sought to create a nomogram predicting probability of ypN+ after NAC for cN0 nmMIBC and determine association with overall survival (OS). We reviewed the National Cancer Database for patients with cT2-4N0M0 urothelial carcinoma of the bladder receiving multiagent NAC and surgery from 2004 to 2020. Following a data split, univariate logistic regression identified variables associated with ypN+ at P < .05. Eligible variables were used for multivariate logistic regression and nomogram generation. A threshold for 95% sensitivity defined high- and low-risk groups for ypN+. Fine–Gray models assessed ypN+ risk group and OS, accounting for competing risks of surgical mortality. A total of 6194 patients were identified with a median follow-up of 39.5 months (interquartile range [IQR], 20.5-67.2 months). Most patients had high-grade (97.7%) cT2 disease (70.8%) with nonpapillary urothelial histology (67.3%) and initiated NAC at a median of 41.0 days after diagnosis (IQR, 28.0-59.0 days).The nomogram included age in decades (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.87–1.03; P = .172), weeks from diagnosis to NAC (OR, 1.02; 95% CI, 1.01-1.04; P = .004), nonpapillary histology (OR, 1.17; 95% CI, 0.99-1.39; P = .068), and clinical T-stage. Within the testing cohort, ypN+ was found in 392 (22.8%) high-risk and 12 (8.0%) low-risk patients (P < .001), with median OS of 36.1 and 74.0 months, respectively (P < .001). High-risk patients had worse OS despite competing risks of 30-day (subdistribution hazard ratio [SHR], 1.80; 95% CI, 1.49-2.18; P < .001) and 90-day surgical mortality (SHR, 1.68; 95% CI, 1.39-2.04; P < .001). This is the first study to provide a tool for predicting ypN+ and prognosticate worse OS in primarily high-grade nmMIBC and could select patients for alternative neoadjuvant therapy and facilitate future study.