Background: Staging of T3 thyroid cancer includes criteria for size (greater than 4 cm) and minimal extrathyroidal extension (ETE). Improvements in pathologic identification of minimal ETE results in large numbers of clinically T1 and T2 tumors being upstaged to pathologic T3 tumors. Practice guidelines do not distinguish between small or large tumors once ETE is identified, which may result in more intensive treatment for small tumors. The effect of this pathologic upstaging on prognosis is unknown. The aim of this study was to investigate the impact of tumor size in patients with minimal ETE in differentiated thyroid cancer.
Methods: A retrospective review of 869 patients surgically treated at the University of Texas MD Anderson Cancer Center for differentiated thyroid cancer between 1997 and 2014 was completed. Inclusion criteria was pathologically diagnosed T3 differentiated thyroid cancer. Primary outcome measure was disease-free survival, defined as the time from primary surgery to locoregional recurrence, distant metastasis or death due to disease. Kaplan-Meier modeling was utilized to assess survival.
Results: Three hundred fifty-four patients with median follow-up of 21 months (range=0-140 months) had pathologic T3 disease. One hundred seventy-six tumors (56.6%) were staged clinically as T1 preoperatively, 105 (33.8%) as T2, and 30 (9.6%) as T3. Three hundred twenty-eight (92.7%) tumors demonstrated ETE. Of patients with ETE, 186 tumors (56.7%) were ≤2 cm, 110 (33.5%) were 2-4 cm, and 32 (9.8%) were >4 cm. Patients with pathologic T3 tumors were divided into 4 comparison groups according to size and presence of ETE. Five-year DFS was 61.4% in tumors >4 cm without ETE, 62.8% in tumors >4 cm with ETE, 93.9% in tumors 2-4 cm with ETE, and 92.1% in tumors ≤2 cm with ETE (Log-rank p<0.001). This is in comparison to a 98.9% 5-year DFS in T2 tumors (2-4 cm without ETE) and 98.5% in T1 tumors (≤2 cm without ETE) from the same cohort at our institution. For tumors ≤4 cm with ETE, 9 (3.1%) patients failed due to locoregional recurrence and 10 (3.5%) due to distant metastatic disease. For tumors >4 cm with or without ETE, 5 (8.6%) patients failed due to locoregional recurrence and 16 (27.6%) due to distant metastatic disease. There were no significant differences between the four groups for locoregional control but patients with tumors >4 cm with ETE demonstrated significantly greater failures due to distant metastatic disease (N=12, p<0.001). Of all patients with pathologic T3 disease, 234 patients (66.1%) underwent adjuvant radioactive iodine (RAI) treatment which did not differ between the 4 comparison groups (p=0.238).
Conclusion: Patients with tumors larger than 4 cm had worse DFS compared to patients with smaller tumors regardless of ETE status. ETE status did not confer a statistically significantly decreased DFS among patients with similar tumor size. The role of ETE in upstaging tumors smaller than 4 cm in differentiated thyroid cancer should be further characterized to determine if less intense treatment strategies are