Survival Outcomes of Medullary Thyroid Cancer With and Without Amyloid Deposition

Objective: Amyloid deposition within tumor stroma is a distinctive histologic feature of medullary thyroid cancer (MTC). However, its prognostic significance remains uncertain. We aimed to elucidate the impact of amyloid status on survival outcomes in a large cohort. Methods: The Surveillance, Epidemiology, and End Results registry was queried to identify patients diagnosed with MTC from 2000 to 2019. Patients with amyloid-positive (International Classification of Diseases for Oncology, third edition code 8345/3) and amyloid negative (International Classification of Diseases for Oncology, third edition code 8510/3) tumors were analyzed. Overall and disease-specific survival were compared between matched cohorts using Kaplan -Meier and Cox proportional hazards analyses. Results: Of the 2526 MTC patients, 511 of which were amyloid-positive and 2015 that were amyloid negative. Amyloid-positive patients displayed lower T stage (T3/4: 28% vs 85%, P < .001) and less extrathyroidal extension (11.3% vs 81.6%, P < .001). No difference in distant metastasis rate was observed between groups (14.5% vs 14.4%, P = .98). However, amyloid-positive patients showed a tendency for distal lymph node metastasis (1.2% vs 0.3%, P = .020). On univariate analysis, amyloid-positive status showed comparable overall survival times (mean 172.2 vs 177.8 months, P =.17), but a trend toward worse cancerspecific survival (hazard ratios [HR] = 1.31, 95% CI = 0.99-1.71, P = .051). After adjusting for covariates, amyloid deposition did not independently predict overall (HR =1.15, 95% CI = 0.91-1.47, P =.25) or cancerspecific survival (HR = 1.30, 95% CI = 0.96-1.77, P = .09). Initiating therapy later than 1 month following diagnosis was associated with worse overall survival (HR = 1.25, 95% CI = 1.02-1.54, P = .029). Conclusions: The presence of amyloid in MTC paradoxically associates with lower T stage yet exhibits a trend toward worse cancer-specific mortality. Amyloid deposition alone does not independently infiuence prognosis. Delayed treatment adversely impacted overall survival.