1. Papillary Thyroid Microcarcinoma : A Report of Impact of Initial Therapy in 2035 Patients Jeonghun Lee, Su Han Seo, Euy Young Soh Department of Surgery, Ajou University

2. Introduction Papillary thyroid carcinoma ① accounts for up to 80% of thyroid cancer ② papillary microcarcinoma : 36~60% of papillary thyroid cancer Discrepancy of treatment strategies ① geographical discrepancy : Western vs. Japan a. total thyroidectomy vs. lobectomy b. therapeutic vs. prophylactic CCND c. radioiodine therapy ② temporal discrepancy : at Mayo Clinic (Hay et al) a. 1940~54 - most lobectomy and no RAI b. 1985~ - most total thyroidectomy and 50% RAI therapy

3. Prognostic factors for recurrence - different among the institutions Buffet et al ( Europ J endo 2012 ) : LN metastasis, multifocality, male, total size of multifocal tumor>20mm) Kim TY et al ( BMC cancer 2008 ) : male, lateral cervical LN metastasis Chow et al ( Cancer 2003 ) : multifocality, limited surgery Hay et al ( Surgery 1992 ) : LN metastasis, limited surgery Introduction

4. Purpose : To investigate the prognostic factors for recurrence in PTMC patients.

5. Materials and Methods Periods : Jan.1994 ~ Oct. 2010 Patients : 2035 PTMC patients who underwent thyroidectomy at Ajou University Hospital Inclusion criteria ① papillary thyroid microcarcinoma ② underwent primary surgical therapy at Ajou University Hospital

6. Strategy for papillary thyroid cancer at Ajou University Hospital ① Lobectomy : papillary thyroid caner < 1cm, no familial history, no capsular invasion, no multifocality and no LN metastasis. ② Central compartment LN dissection(CCND) : if malignancy on FNA cytology or frozen section biopsy  prophylactic CCND was performed ③ Lateral compartment LN dissection : therapeutic LN dissection Materials and Methods

7. Mean follow-up duration : 33.8 months Materials and Methods WIFTC : wide invasive FTC, MIFTC : minimal invasive FTC MTC : medullary thyroid cancer, HCC : Hurthle cell cancer

8. Clinicopathologic features VariablesClinical pathologic features Age45.3±11.081 Gender(M/F)1:5.8 Total thyroidectomy1244(61.5%) Central neck dissection 1881(92.4%) Lateral neck dissection108 (5.3%) Radioactive iodine(RAI) therapy503 (24.7%) Tumor size0.63±0.25 ETE1016 (49.9%) Multiplicity612(30.1%) T stageT 11021 (50.1%) T3958(47.1%) T428(1.4%) N stageN01184(58.2%) N1a609(29.9%) N1b88(4.3%) VariablesClinical pathologic features M stage7 (0.3%) TNMStage I1374(67.5%) Stage II3(0.1%) Stage III528(25.9%) Stage IV582.9%) BRAF mutation393/519(75.7%) RecurrenceRemnant thyroid16/41 (39.0%) Central neck, dissected previously 2/41 (4.8%) Lateral neck25/41 (60.9%) Distant metastasis3/41(7.3%) Unknown site2/41 (4.8%) Permanent hypoparathyroidism(12months) 57/1244(4.5%) Postoperative hoarseness 38/2034(1.9%)

9. Univariate statistical analysis for recurrence VariablesPatients No. (%)Recurrences No.(%) 10 yr recurrence-free rate (%) Univariate analysis, p Gender0.361 Males298(14.6%)8(2.6%)79.3% Females1736(85.3%)33(1.9%)94.6% Age at first treatment0.915 < 45yr1026(50.4%)22(2.1%)92.7% ≥ 45yr1008(49.5%)19(1.8%)91.3% Extent of thyroidectomy0.639 Total1244(61.7%)26(2.1%)91.2% Less than total772(38.2%)14(1.9%)93.5% Primary tumor size0.409 ≤ 5mm860(42.2%)13(1.5%)91.5% >5mm1174(57.7%)28(2.3%)92.3%

10. VariablesPatients No. (%)Recurrences No.(%) 10 yr recurrence-free rate (%) Univariate analysis, p Extrathyroidal extension0.129 Absent1024(50.3%)13(1.2%)95.0% Present988(48.6%)26(2.6%)89.7% Multiplicity0.586 Absent1412(69.7%)26(2.0%)94.1% Present612(30.2%)13(2.2%)87.3% T stage0.208 T11024(50.4%)15(1.4%)94.5% T3960(47.2%)23(2.4%)89.9% T428(1.4%)1(3.5%)96.3% N stage<0.0001 Nx153(7.6%)3(1.9%)90.5% N01184(58.2%)11(0.9%)98.1% N1a609(29.9%)17(2.7%)92.6% N1b88(4.3%)10(11.3%)67.3% RAI therapy<0.0001 Yes503(24.7%)24(4.6%)74.3% No1531(75.3%)17(1.1%)97.9% Univariate statistical analysis for recurrence

11. Clinicopathologic features No RAIRAIP-value Age(year)45.145.90.168 Tumor size(cm)0.590.74<0.001 Total LN metastasis0.582.66<0.001 ETEpresent Multifocalitypresent22.2%54.8%<0.001 T stageT340.3%70.3%<0.001 T40.4%4.2% N stageN1a23.0%56.5%<0.001 N1b1.3%15.8% Univariate statistical analysis for recurrence RAI therapy 97.9% 74.3%

12. N stageN0N1aN1b P-value N00.01<0.01 N1a0.01<0.01 N1b<0.01 Univariate statistical analysis for recurrence N stage 98.1% 92.6% 67.3 % 90.5%

13. Multivariate statistical analysis for recurrence Variablesp-valueExp(B) RAI therapy0.1631.7 N stage0.001 N1a0.1092.0 N1b<0.0016.7

14. Summary Prognostic factors for recurrence ① Extent of thyroidectomy : no significant factor ② RAI therapy : no significant factor in multivariate analysis ③ N stage : only significant factor for recurrence in multivariate analysis - N1a : 2 riskier than N0 ( p= 0.01) - N1b : 6.7 riskier than N0 (p< 0.01) Complication ① postoperative hoarseness : 1.9% ② permanent hypoparathyroidism : 4.5% (2.7% * ~12% # ) *Caliskan et al 2012 Endocrine J # Mitra et al 2011 J Laryngol Otol

15. Limited thyroidectomy : maybe sufficient for initial surgery for PTMC patients Prophylactic central LN dissection : can be performed for PTMC patients for predicting prognosis accurately, : however, performed by skilled surgeon because of higher incidence of permanent hypoparathyroidism Limitation of study : short-term follow-up duration Conclusion