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

Abstract

Background. 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. Aim. To determine the effect of time to treatment initiation (TTI) on mortality in MCC and to determine the predictors of TTI itself. Methods. 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. Results. In total, 12 157 patients [7491 (61.6%) men, 4666 (38.4%) women; mean AE SD age 74.4 AE 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). Conclusion.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.

Delayed time to radiation and overall survival in Merkel cell carcinoma

“…This is consistent with some prior studies using the NCDB. [9][10][11] From the splines (Figure S1), IT appears that time to surgery may play more of a role than time from surgery to radiation. However, the present study had a positive finding when looking at time from diagnosis to radiation.…”

“…8 More recent studies using the National Cancer Database have found no link between survival and time from surgery to radiation treatment, 9,10 or between survival and time from diagnosis to surgery. 11 Anecdotally, we have noted that depending on clinical course, treatment choices, and access to care, time to radiation for individual patients may vary greatly. We sought to use a comprehensive, national cohort to investigate factors influencing time to initiation of RT and its impact on survival among MCC patients who received surgical excision and adjuvant radiation.…”

Overall Survival After Mohs Surgery for Early-Stage Merkel Cell Carcinoma

“…The NCDB is a nationwide clinical surveillance resource data set that includes approximately 70% of all newly diagnosed malignant neoplasms in the US from more than 1500 cancer programs . Data from the NCDB have been used in multiple previous studies of cutaneous oncologic outcomes . This study was deemed not to be human participant research and was therefore exempt from institutional review board review by the New York University Langone Institutional Review Board.…”

“…27,28 Data from the NCDB have been used in multiple previous studies of cutaneous oncologic outcomes. 15,[29][30][31][32] This study was deemed not to be human participant research and was therefore exempt from institutional review board review by the New York University Langone Institutional Review Board. Informed consent was not obtained because this was not human participant research.…”

Challenges documenting racial disparities in Merkel cell carcinoma

“… 6 , 7 However, multivariate analysis of data from SEER 17 (1988–2012) and NCDB (2004–2016) failed to establish an association between race and survival. 4 , 9 Studies to resolve these inconsistencies and better understand MCC disparities are needed.…”