Predictors of time to definitive surgery and survival in Merkel cell carcinoma: analysis of the US National Cancer Database.

Abstract

Merkel cell carcinoma (MCC) is an aggressive cancer, and it has been suggested that earlier treatment would allow for better patient outcomes. However, the causes of delays in the initiation of treatment and the effects of delayed treatment on survival of patients have not fully been explored, and the effects of treatment delays for MCC are not yet fully understood. To determine the effect of time to treatment initiation (TTI) on mortality in MCC and to determine the predictors of TTI itself. This was a retrospective cohort analysis of the US National Cancer Database (NCDB) for cases of MCC from 2004 to 2016, excluding individuals with Stage IV MCC, as surgery is not the preferred treatment for this group. The time difference between initial biopsy of MCC and definitive surgery (TTI) was stratified into five groups by 30-day intervals. In total, 12 157 patients [7491 (61.6%) men, 4666 (38.4%) women; mean ± SD age 74.4 ± 10.9 years] were included in the study. A risk for longer TTI was seen in black individuals (OR = 1.7, 95% CI 1.2-2.6) and in elderly individuals aged > 70 years (OR = 1.7, 95% CI 1.2-2.5). Kaplan-Meier survival analysis showed that individuals with TTI < 30 days had a significantly longer overall survival than those with TTI > 120 days (6.1 vs. 4.8 years, P < 0.001). However, after controlling for clinical and tumour factors in Cox multivariable analysis, no difference in survival was noted for TTI < 30 days and TTI > 120 days [hazard ratio (HR) = 0.9, 95% CI 0.8-1.1). Worse outcomes were also associated with increasing age (HR = 2.0, 95% CI 1.7-2.5), male sex (HR = 1.2, 95% CI 1.2-1.3), higher Charlson-Deyo comorbidity score (HR = 1.4, 95% CI 1.3-1.5), lack of radiation therapy (HR = 0.8, 95% CI 0.8-0.9), lack of private insurance (HR = 0.7, 95% CI 0.6-1.0), and use of surgical technique other than Mohs micrographic surgery or wide local excision (HR = 1.2, 95% CI 1.2-1.3). Although TTI is a useful prognostic metric in isolated survival analysis, its utility declines when other factors are controlled for in the analysis. Age, radiotherapy, type of surgery performed, comorbidities, tumour size and lymph node involvement may be important predictors of survival.