Validation of Lymph Node Thresholds as Prognostic Factors in Medullary Thyroid Cancer Staging.

INTRODUCTION: The current AJCC medullary thyroid cancer (MTC) staging system anatomically stratifies lymph node (LN) status but does not incorporate quantitative assessment of LN metastases. Our past work identified ≥ 8 positive LNs and LN ratio (LNR) ≥ 14% as associated with significantly increased MTC-specific mortality. In this study, we 1) validate these thresholds using the NCDB and 2) compare them to the current AJCC staging system. METHODS: In this retrospective cohort study, patients with MTC were abstracted from NCDB (2004-2020). Chi-square and Fisher's exact tests compared categorical variables, and t-tests continuous variables. Overall survival (OS) was estimated with Kaplan-Meier and log-rank testing. Cox Proportional hazards models estimated the association of LN thresholds with OS after adjusting for covariates. RESULTS: There were 5685 patients (median age: 55 years; 56.4% female; 74.3% non-Hispanic White). The 5-year OS was 78.2% (95% confidence interval [CI] 76.4-79.9) for LNR ≥ 14% and 93.9% (95% CI 92.9-94.8) for LNR < 14%. For ≥ 8 positive LNs, 5-year OS was 77.2% (95% CI 74.8-79.4) versus 90.4% (95% CI 89.4-91.4) for < 8. After adjustment, LNR ≥ 14% was associated with a 44% increased mortality risk (hazard ratio [HR] 1.44, 95% CI 1.10-1.88, p = 0.008); ≥ 8 positive LNs conferred a 37% increased hazard (HR 1.37, 95% CI 1.13-1.66, p = 0.001). Neither AJCC N-stage nor nodal status was associated with a significant adjusted hazard difference. CONCLUSIONS: Previously identified prognostic LN thresholds for MTC were valid in the NCDB. A LNR ≥ 14% and ≥ 8 positive LNs provide better prognostic discrimination than the current AJCC system and aid refinement of the current MTC staging system.

Duke Scholars

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