Trends in Treatment and Comparison of Outcomes in Lymph Node Positive Bladder Cancer

INTRODUCTION AND OBJECTIVES: While extensive research has assessed treatment outcomes in muscle invasive bladder cancer, lymph node positive disease (LN+) has traditionally been excluded from randomized studies or grouped with metastatic disease. Though still potentially curable if treated before systemic metastasis, treatment for LN+ disease is not standardized. This study seeks to compare outcomes and demonstrate trends in treatment for LN+ bladder cancer. METHODS: We performed a retrospective cohort study using the National Cancer Database (2006-2014) and identified 1869 cT2-4N1-3M0 bladder cancer patients treated with (1) radical cystectomy (RC), (2) neoadjuvant chemotherapy (NAC) + RC, (3) adjuvant chemotherapy (AC) + RC, (4) radiation + chemotherapy, (5) chemotherapy alone, or (6) no treatment/palliative care only. The primary outcome was survival by treatment, analyzed using Kaplan-Meier and multivariable Cox-proportional hazards regression. Secondary outcomes included pathologic down-staging, analyzed using univariable/multivariable logistic regression models. A univariable logistic regression model of treatment by year was used to identify treatment trends. Multivariable models were adjusted for confounding demographic, facility, and clinicopathologic variables. RESULTS: Among 1869 patients (cN1, 48%; cN2, 44%; cN3 8%), 567 underwent RC, 418 underwent NAC, 591 underwent AC, 61 underwent radiation + chemotherapy, 136 underwent chemotherapy alone, and 96 had no definitive treatment. Overall survival did not differ between NAC and AC, but both had improved survival compared to RC alone. All other treatment groups had worse survival outcomes in comparison to NAC. When comparing NAC to RC alone, down-staging to pT0 (adjusted odds ratio [aOR]=26.39) and pN0 (aOR=6.88) was higher for NAC. Overall, utilization of NAC and no treatment has increased, use of AC and RC alone has declined, and use of chemotherapy and radiation without surgery has not changed. CONCLUSIONS: Combined chemotherapy and RC is associated with improved outcomes for LN+ bladder cancer compared to RC or chemotherapy alone, although there is no significant difference between NAC and AC. Use of radiation and chemotherapy without RC has stayed consistent and is associated with worse oncologic outcomes compared to RC with perioperative chemotherapy, but no significant difference compared to RC or chemotherapy alone