Introduction:

The early years of adoption of any novel treatment is the optimal setting to study and address potential barriers to accessing and utilizing evidence-based therapy. This is particularly relevant for immunotherapy, given the tremendous therapeutic potential of immune checkpoint inhibitors for locally advanced/metastatic urothelial carcinoma in select patients with otherwise limited options. The recent advent of the age of immunotherapy in bladder cancer presents an early opportunity to assess barriers to receiving novel agents. We aim to identify the modifiable sociodemographic factors associated with failure to receive recommended immunotherapy in a vulnerable patient population with metastatic bladder cancer.

Methods:

A retrospective cohort analysis of the National Cancer Database (NCDB) hospital-based registry was performed to identify trends in immunotherapy utilization for bladder urothelial carcinoma (UC) from 2014–2020. Adult patients diagnosed with node-positive or metastatic urothelial carcinoma (mUC) who were recommended or planned to receive immunotherapy as the initial systemic treatment were included. A multivariable Fine and Gray competing-risk analysis was performed to assess delays in time to receipt of immunotherapy. A multivariable logistic regression model was used to assess patient-specific, disease-specific, geo-temporal and socioeconomic covariates associated with failure to receive immunotherapy. Survival analyses were conducted with Kaplan-Meier and Cox proportional hazards model with inverse probability of treatment weighting (IPTW) to assess overall survival (OS) of patients receiving immunotherapy compared to patients who failed to receive immunotherapy. All analyses were performed using Stata 17.0 (College Station, TX).

Results:

Of 23,168 patients diagnosed with mUC from 2014–2020, 2,244 patients (9.7%) were recommended to receive immunotherapy as the first systemic treatment, of which 1,801 (80.3%) received immunotherapy as planned. On multivariable analysis, not having any insurance (OR 2.82, 95% CI 1.29–6.16) or having Medicaid insurance (OR 1.83, 95% CI 1.03–3.24) were the modifiable barriers with the largest effect sizes associated with failure to receive immunotherapy. Other barriers to receiving immunotherapy included non-academic facility (OR 1.78, 95% CI 1.38–2.29), higher Charlson-Deyo score (OR 1.56, 95% CI 1.11–2.17), female sex (OR 1.42, 95% CI 1.12—1.80), and older age (OR 1.02, 95% CI 1.12–1.80). The median time to immunotherapy initiation was 2.0 months with faster initiation during more recent years (SHR 1.13, 95% CI 1.09–1.17). The immunotherapy group demonstrated improved OS (HR 0.28, 95% CI 0.23–0.32) compared with the group that failed to receive immunotherapy.

Conclusion:

Lack of insurance or Medicaid coverage was associated with failure to receive immunotherapy for metastatic bladder cancer, with subsequent implications for overall survival. This insurance barrier may be exacerbated further during the early years of adoption of any novel therapy, when outdated insurance coverage policies fail to keep up with rapidly evolving scientific evidence. 

Funding: N/A