Introduction:

The optimal management of bladder cancer with clinically positive regional lymph node (cN+) remains as a challenge. In analysis of patients with cN+ via the National Cancer Data Base bladder cancer, combined treatment with radical cystectomy (RC) and chemotherapy versus RC or chemotherapy alone was associated with a better overall survival outcome (Galsky et al. 2016). However, despite advancement in multimodal approaches, the role of local definitive therapy in addition to systemic treatment in cN+ bladder cancer is yet to be determined. Herein, we sought to investigate the role of RC in management of patients with cN+ bladder cancer at US Veterans Health Administration Facilities. 

Methods:

We identified patients diagnosed with non-metastatic cN+ bladder cancer between 2000-2017 using the Department of Veterans Affairs (VA) Informatics and Computing Infrastructure (VINCI). We used a combination of database/registry coded values and chart review to assemble tumor, treatment, comorbidity, and sociodemographic data. Clinical nodal status was defined as the highest clinical N stage received within 90 days after diagnosis. To minimize mortality bias, we excluded patients who died within 90 days of diagnosis.  We divided the cohort based on receiving RC to chemotherapy only group or RC group. The Propensity score matching was performed based on predictors of receipt of RC. Multivariable Cox proportional hazards models and Kaplan-Meier survival curves were used to evaluate overall survival (OS).

Results:

Of 475 patients with non-metastatic cN+ bladder cancer, 170 patients underwent RC with peri-operative chemotherapy. After propensity matching, 156 patients in each group were included in analysis. 84(54%) and 72(46%) patients in RC group received neoadjuvant and adjuvant chemotherapy, respectively. 66 patients (42%) in RC group and 62(40%) patients in chemotherapy group had clinical N1 disease (p=0.75).  In multivariable logistic model, RC was associated with improved OS (HR 0.65, 95%CI 0.50-0.84, p=0.001). In subset analysis, RC was only associated with improved OS in patients with clinical N1 disease (0.54, 95%CI 0.33-0.87, p=0.01). There was no OS benefit from RC in patients with clinical N2/N3 bladder cancer (0.75, 95%CI 0.52-1.07, p=0.11). In sensitivity analysis, RC after neoadjuvant chemotherapy also improved OS (0.63, 95%CI 0.46-0.87, p=0.01). Kaplan-Meier survival curves were demonstrated in Figure1.  

Conclusion:

Patients with bladder cancer and limited regional lymph node involvement (clinical N1), who underwent RC in addition to chemotherapy have an improved OS compared with patients who did not undergo RC. This study suggests RC should be considered, as part of multimodal treatment, in subset of patients with clinically regional lymph node metastasis. More studies with focus of cancer specific outcomes are needed to validate these findings.

Funding: N/A