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

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.

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.

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.

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.