Abstract

Purpose/objective(s)Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neoplasm traditionally managed with surgical resection followed by radiotherapy (RT). With the recent approval of checkpoint inhibitors, chemotherapy is less commonly utilized. We analyzed the impact of RT and chemotherapy on overall survival (OS) in patients with MCC using Surveillance, Epidemiology, and End Results (SEER), a population-level database.Materials and methodsWe performed retrospective analyses on SEER 18 Custom Data registries for MCC (ICD-0-3 8247). Data from 1980 to 2016 was queried for analysis, and an initial list of 9,792 patients was populated (ICD: C00, C07.9, C44, C80.9). Selection for cases with chemotherapy and RT status, single primary tumor, primary tumor location and surgery treatment type yielded 5,002 cases for analysis. Baseline characteristics were compared with Chi-square or Mann-Whitney U test. Univariate and multivariable analysis using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment weighting (IPTW) was used to account for indication bias.ResultsMedian follow-up time was 178 months (68 to 217 months). Independent prognostic factors positively correlated with increased OS, for both unadjusted Multivariate analysis and IPTW adjusted MVA were age, male sex, year of diagnosis, stage, RT status, and chemotherapy status. On adjusted MVA, use of chemotherapy was associated with worse OS (hazard ratio: 1.22 [95% CI 1.1-1.35], p<0.001), whereas RT was associated with improved OS (HR:0.9 [95% CI, 0.83-0.97], p=0.008).ConclusionsThe current study demonstrates that RT is associated with improved survival for patients with MCC. Chemotherapy was associated with worse OS. This supports the recent clinical shift towards immune checkpoints inhibitors as standard of care in the metastatic setting, and promising trials in the adjuvant and advanced settings.

Highlights

  • Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy of neuroendocrine origin

  • Independent prognostic factors positively correlated with increased overall survival (OS), for both unadjusted Multivariate analysis and inverse probability of treatment weighting (IPTW) adjusted MVA were age, male sex, year of diagnosis, stage, radiation therapy (RT) status, and chemotherapy status

  • On adjusted MVA, use of chemotherapy was associated with worse OS, whereas RT was associated with improved OS (HR:0.9 [95% CI, 0.83-0.97], p=0.008)

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Summary

Introduction

Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy of neuroendocrine origin. MCC has high metastatic potential, and many patients develop recurrent disease. In a modern study by Fields et al, 108 of 364 patients (29.7%) with Stage I-III MCC who underwent complete resection experienced recurrences at local (10%), in-transit (11%), nodal (40%), and distant (39%) sites [2], and most recurrences occurred within two years. Higher recurrence rates are associated with advanced stage, age > 70, tumor size > 2 cm, positive lymph node status, lymphovascular stromal invasion (LVSI), and male sex [3,4]. Surgical resection with wide margins has been the mainstay of therapy. Given the high rates of locoregional relapse (LRR) and radiosensitivity of MCC, radiation therapy (RT) has been increasingly

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