Delayed time to radiation and overall survival in Merkel cell carcinoma

Abstract

Background: Clinically localized Merkel cell carcinoma (MCC) is commonly treated with surgical excision and radiotherapy. The relationship between time to adjuvant radiotherapy and overall survival (OS) remains understudied. Methods: This retrospective study used data from the National Cancer Database (2006–2019). Patients with clinically localized MCC who received surgical excision and adjuvant radiotherapy were included. Multivariate regressions were used to account for various patient and tumor factors. The primary outcome was 5-year OS, and the secondary outcome was time from diagnosis to adjuvant radiation (TTR). Results: Of the 1965 patients included, most were male (n = 1242, 63.2%) and white (n = 1915, 97.5%), and the median age was 74 years (interquartile range [IQR]: 66–81). The median TTR was 83 days (IQR: 65–106). A total of 83.6% of patients received radiotherapy to the primary site, 21.3% to the draining nodal basin, 17.1% to both, and 12.2% whose target location of radiotherapy was not recorded in the data. TTR of ≥79 days (the 45th percentile) was associated with worse OS on both univariate and multivariate analyses (log-rank p = 0.0014; hazard ratio [HR]: 1.258, 95% confidence interval [CI]: 1.055–1.500, p = 0.010). This persisted on sub-analyses of patients <80 years old (n = 1407; HR: 1.380, 95% CI: 1.080–1.764, p = 0.010) and of patients with Charlson comorbidity index (CCI) of 0 (n = 1411; HR: 1.284, 95% CI: 1.034–1.595, p = 0.024). Factors associated with delayed TTR included greater age (p = 0.039), male sex (p = 0.04), CCI > 1 (p = 0.036), academic facility (p < 0.001), rural county (p = 0.034), AJCC T2 stage (p = 0.010), negative margins (p = 0.017), 2+ pathologically positive regional nodes (p = 0.011), and margin size >2 cm (p = 0.015). Conclusions: Delayed radiotherapy (≥79 days) was associated with worse OS of MCC patients. Further study in controlled cohorts is needed to ascertain this relationship.