Patterns of Recurrence and Prognosis in Pathologic Stage I and II Merkel Cell Carcinoma: A multi-center, retrospective cohort analysis

Published: 12 May 2022| Version 1 | DOI: 10.17632/g3tbnysh5p.1
Andrew Tieniber


Table 1. Baseline patient, tumor, and treatment characteristics of all patients with surgically resected pathologic stage I and II Merkel cell carcinoma. IQR, interquartile range; AJCC, American Joint Committee on Cancer. * indicates significance Table 2: Univariate and reduction multivariable Cox proportional hazard regression analysis examining factors associated with all-site recurrence in patients with pathologic stage I-II Merkel cell carcinoma. AJCC, American Joint Committee on Cancer; TILs, tumor infiltrating lymphocytes; HR, hazard ratio; CI, confidence interval. * indicates significance


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Patient variables Patient characteristics considered in the study were age at diagnosis, sex, race (White, Black, Asian, and other/unknown), and history of immune compromise including solid organ transplant, hematologic malignancies, or autoimmune diseases. All primary tumor characteristics were obtained from prior pathology reports at the respective institutions. Tumor factors that were considered in the analysis included site of the primary tumor (extremity, axial/trunk, or head/neck), tumor size (mm), tumor depth (mm), AJCC pathologic T staging group, AJCC pathologic stage, lymphovascular invasion (LVI), tumor extension, tumor infiltrating lymphocytes (absent, brisk, and non-brisk), presence of microsatellitosis, nodular growth, and infiltrate growth. Treatment factors that were utilized in analysis included receipt of radiation therapy to the primary lesion site. Tumor size was further dichotomized to <14 mm and ≥14 mm based on the median tumor size present in the patient population. Patient follow-up varied among institutions but included clinical visits with physical exam every 3-6 months and nodal ultrasound and cross-sectional imaging in some patients every 6-12 months. Statistical analyses The primary endpoint of this study was all-site disease recurrence, including local, in-transit, nodal, and distant disease; the secondary outcome of this study was disease-specific survival (DSS) by pattern of first-site relapse. Regional recurrence was defined as either in-transit or regional lymph node disease. Univariate analysis for categorical variables was performed using Pearson’s χ² test and for continuous variables using the Wilcoxon rank-sum test. Time to recurrence (TTR) and DSS were calculated by using the date of surgery as the start time for each event; patients who did not experience recurrence were censored at the date of last follow-up. A pairwise comparison of TTR times among patients with disease recurrence was based on estimated marginal means using a Bonferroni correction. Predictors of all-site recurrence were determined based on Cox proportional hazard regression analyses; covariates included in a reduced multivariable regression were determined based on those factors independently associated with all-site recurrence based on univariate analyses. DSS was analyzed using the Kaplan-Meier method and compared using the stratified log-rank test. All tests performed for this study were two-sided and all P values ≤0.05 were considered statistically significant. Statistical analyses for this study were performed using Stata for Windows version 16.1.8


Oncology, Skin Cancer, Merkel Cell Carcinoma, Prognosis, Clinical Outcomes Research