Management of Papillary Ca Thyroid JHSGR Management of Papillary Ca Thyroid Chris Cheng Tsz Ling Princess Margaret Hospital

Introduction Thyroid carcinoma has the fastest rising incidence of all major cancers, ↑4% per year Papillary thyroid carcinoma(PTC) is the most common type of differentiated thyroid carcinoma, incidence x 2 throughout 25 years Excellent prognosis, 10-year cancer specific survival rate >90% Locoregional recurrence (LRR) is a major cause of disease morbidity Grubbs EG, Rich TA, Li G, et al. Recent advances in thyroid cancer. Curr Probl Surg 2008;45:156 –250 Cancer incidence and mortality in Hong Kong 1983–2008: Hong Kong Cancer Registry, Hong Kong ADD HK INCIDENCE OF THRYOID CANCER AND PAPILLARY THYROID CANCER

Agenda The optimal extent of surgery Prophylactic central neck LN dissection Rationale for use of adjuvant radioactive iodine (RAI) remnant ablation Agenda

Thyroidectomy

Total/Near total Thyroidectomy Vs Lobectomy Total thyroidectomy (n=43227) Vs Lobectomy (n=8946) ≥ 1cm CA thyroid, Lobectomy was associated with 15% higher risk of recurrence (p=0.04) 31% higher risk of death (p=0.009) < 1cm CA thyroid, no difference in recurrence or survival Bilimoria et al. Extent of surgery affects survival for papillary thyroid cancer. Ann Surg 2007 Sep;246(3):375-81 American Thyroid Association recommendation: Lobectomy: for <1cm, low risk, unifocal, intrathyroidal papillary carcinoma without cervical LN or history of head & neck irradiation Near-total / Total thyroidectomy: for >1cm

Neck LN Dissection

Neck Dissection Therapeutic - Clinically evident and biopsy proven LN involvement Prophylactic No clinical evidence of LN HOT debate: Prophylactic Central LN dissection(level VI) Neck Dissection

Central neck dissection (minimum) Pre-laryngeal Pre-tracheal Para-tracheal Central neck dissection may be extended to: Retropharyngeal Retroesophageal Paralaryngopharyngeal (superior vascular pedicle) Superior mediastinal (inferior to innominate artery) ATA Guideline. Consensus Statement on the Terminology and Classification of Central Neck Dissection for Thyroid Cancer. Thyroid. Volume 19, Number 11, 2009

Central Neck dissection SEER (Surveillance, Epidemiology, and End Results) database 9904 Papillary thyroid cancer Cervical LN met in papillary cancer of Age>45 Independent risk factor for decreased survival The most common site for lymph node metastases and DTC recurrence is within the central compartment Roh JL et al. Total thyroidectomy plus neck dissection in differentiated papillary thyroid carcinoma patients: pattern of nodal metastasis, morbidity, recurrence, and postoperative levels of serum parathyroid hormone. Ann Surg 2007 245:604–610. Central neck dissection may convert some patients from cN0 to pathologic N1a

Central Neck dissection Mayo clinic 60-year observation in 900 patients with <1cm microcarcinoma In 450 patients with any form of LN surgery done, 30% lymph node involvement at initial surgery 80% recurrence at central LN Hay ID et al. Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period. Surgery 2009. 144:980–987.

CND may reduce recurrence In 950 Papillary thyroid cancer patients Stage I 45%, Stage II 25%, Stage III 22%, Stage IV 6% 75% LN dissection done (mostly CND only) Recurrences LN dissection: 6.8% No LN dissection: 16.5% (p<0.001) Stage I (1%), Stage II (6%), Stage III (6%), Stage IV (77%) No difference in 10-yr / 15-yr survival Toniato A et al. Papillary thyroid carcinoma: factors influencing recurrence and survival. Ann Surg Oncol 2008;15: 1518–1522.

Central Neck Dissection Seems Improve survival in comparing observational studies Tisell LE et al. Improved survival of patients with papillary thyroid cancer after surgical microdissection. World J Surg 1996. 20:854–859.

Central Neck Dissection Increases the proportion of patients who appear disease free with unmeasureable Tg levels 6 months after surgery undetectable TG levels Total thyroidectomy + CND: 72% Total thyroidectomy only: 43% (p<0.001) Sywak M et al. Routine ipsilateral level VI lymphadenectomy reduces postoperative thyroglobulin levels in papillary thyroid cancer. Surgery 2006. 140:1000–1007

Central neck dissection increases complications?

Complications of thyroidectomy alone Vs thyroidectomy + CND Chrisholm et al. Systematic review and meta-analysis of the adverse effects of thyroidectomy combined with central neck dissection as compared with thyroidectomy alone. Laryngoscope 2009 Jun;119(6):1135-9

Complications of thryoidectomy alone Vs thryoidectomy + CND Chrisholm et al. Systematic review and meta-analysis of the adverse effects of thyroidectomy combined with central neck dissection as compared with thyroidectomy alone. Laryngoscope 2009 Jun;119(6):1135-9

Central Neck Dissection All existing literatures are cohort studies No RCT American thyroid association has commented it is NOT feasible to do an RCT on prophylactic central neck dissection Need to randomize 5840 patients to have enough power to show a difference in recurrence or complications! American Thyroid Association Design and Feasibility of a Prospective Randomized Controlled Trial of Prophylactic Central Lymph Node Dissection for Papillary Thyroid Carcinoma. THYROID. Volume 22, Number 3, 2012

Central Neck Dissection Pros ↓ recurrence Lower postop serumTg - To simplify FU and surveillance for recurrence 3)↓ need for reoperation in the central neck Cons ↑ temporary hypoparathyroidism (1- 4%) ↑temporary RLN injury(2-12%)

American Thyroid Association (ATA) guideline – Central neck dissection Prophylactic central-compartment neck dissection (ipsilateral or bilateral) PTC with clinically uninvolved central neck LN, especially for advanced primary tumors (T3 or T4). Recommendation rating: C Near-total or total thyroidectomy without prophylactic central neck dissection for small (T1 or T2), noninvasive, clinically node-negative PTCs. These recommendations should be interpreted in light of available surgical expertise.

Radioactive Iodine Ablation

Role of post thyroidectomy RAI Remnant ablation (to facilitate detection of recurrent disease and initial staging) Adjuvant therapy (to decrease risk of recurrence and disease specific mortality by destroying suspected, but unproven metastatic disease), or RAI therapy (to treat known persistent disease).

↓ Recurrence and cancer death in Stage 2/3 disease Mazzaferri EL, Jhiang SM 1994 Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97:418–428.

RAI improved survival The single most powerful prognostic indicator ↑ increase disease-free interval (p<0.001) ↑ increase survival Samaan Na et al. The results of various modalities of treatment of well differentiated thyroid carcinomas: a retrospective review of 1599 patients. J Clin Endocrinol Metab 1992. 75:714–720.

The National Thyroid Cancer Treatment Cooperative Study Group (NTCTCSG) 2936 patients median follow-up of 3 years Near-total thyroidectomy followed by RAI therapy and aggressive thyroid hormone suppression therapy Improved overall survival of patients with NTCTCSG stage II-IV disease No impact of therapy in stage I disease Jonklaas J et al. Outcomes of patients with differentiated thyroid carcinoma following initial therapy. Thyroid 2006. 16:1229–1242.

Mayo Clinic experience on MACIS low risk papillary thyroid cancer Hay ID, McConahey WM, Goellner JR. Managing patients with papillary thyroid carcinoma: insights gained from the Mayo Clinic’s experience of treating 2,512 consecutive patients during 1940 through 2000. Trans Am Clin Climatol Assoc 2002.113:241–260

RAI in papillary thyroid microcarcinoma RAI after thyroidectomy for <1cm PTM did not reduce recurrence Hay ID et al. Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period. Surgery 2009. 144:980–987.

RAI in papillary cancer RAI did not show benefit in low risk disease Recurrence and survival benefits restricted to: >1.5cm Residual disease following surgery

ATA guideline on RAI remnant ablation SELECTIVE USE

ATA guideline on RAI remnant ablation Recommended for T3-4 or M1 Recommended for selected cases in 1-4cm thyroid cancers with: Lymph node metastases, or high risk features Age >45, tumor invasion, individual histology, incomplete resection Recommendation rating: C NOT recommended for patients with: unifocal cancer <1 cm without other higher risk features Recommendation rating: E multifocal cancer when all foci are <1 cm in the absence other higher risk features

Conclusion Individualized management according to risk stratification Low Vs High risk Total/Near-total Thyroidectomy is standard for >1cm papillary thyroid cancer Prophylactic Central neck dissection is indicated for T3-4 tumors to reduce local recurrence For T1-2 tumors, need to balance benefits and complications RAI mainly indicated for T3-4 & M1 disease

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