Purpose: To evaluate the impact of structural disease progression of metastatic lesions after initial surgery on overall survival (OS) of patients presenting with metastatic medullary thyroid cancer (MTC). We used tumor volume doubling time (TVDT) as a marker of structural disease progression and aimed to correlate the average structural tumor volume doubling time (midDT) with OS in MTC patients after initial surgery. Methods: In this retrospective study, we examined the clinical characteristics; average tumor volume doubling times of neck, lung, and liver metastasis; and disease-specific survival of patients with metastatic MTC. Results: Tumor growth is constant in MTC metastasis, irrespective of location of the metastasis. The median correlation coefficient (r) and the coefficient of determination (r²) were similar in lung metastasis (r = 0.91, r² = 0.95) and liver metastasis (r = 0.88, r² = 0.94), and comparable in neck metastasis (r = 0.73, r² = 0.85). Patients with metastatic MTC with a midDT ≤1 year have a worse prognosis than those with higher midDT (p = 0.002). Those with midDT ≤1 year had a median OS of 11.1 years [confidence interval (CI) 7.4-14.8 years]. In contrast, patients with midDT 1-3 years had a median OS of 16.5 years [CI 10.3-22.6 years]. All patients with midDT ≥3 survived by the end of the follow-up period. Preliminary results suggest that measurement of midDT can predict response to molecular targeted therapies. Conclusions: In conclusion, TVDT is a strong predictor of OS in patients with recurrent or metastatic MTC, can be used as a marker of progression, and potentially can help select patients who may benefit from molecular targeted therapy.

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