Disclosures Nodal Management in Differentiated Thyroid Carcinoma

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1 Disclosures Nodal Management in Differentiated Thyroid Carcinoma Nothing to disclose Jonathan George, MD, MPH Assistant Professor UCSF Head and Neck Oncologic & Endocrine Surgery Objectives Overview Describe anatomy and behavior of thyroid cancer metastases Understand management of neck for primary and recurrent DTC Explain concepts and terminology in neck dissection for thyroid cancer Clinical Epidemiology in DTC Diagnostic Imaging and Biopsy Surgical Management of the Neck Central/ Recurrence 2014 US Data on DTC: Prevalence: 600,360 Incidence: 62,980 Peak age at diagnosis years of age Thyroid cancer on the rise Year Men Women Total ,000 34,000 45,000/year ,000 71,000 92,000/year , , ,000/year CA: A Cancer Journal for Clinicians. 2014, 64(4): Rahib et al. Cancer Research 2014, 74(11). SEER Stat Fact Sheets. Thyroid

2 Incidence M F 1975: : Mortality American Cancer Society. Thyroid cancer year Survival 97.7% Recurrence remains a problem up to 40% Mortality Patients with recurrence higher mortality 30 year FU (N=2883): Recurrence 30% Mortality 9% Grogan RH, et al. AAES 34 th Annual Meeting, Increasing worldwide 15-fold increase in Korea but so is screening Jury is still out Ahn HS et al. Korea s Thyroid Cancer Epidemic Screening and Overdiagnosis. NEJM 371(19), Nov Ahn HS et al. Korea s Thyroid Cancer Epidemic Screening and Overdiagnosis. NEJM 371(19), Nov Risk Group Stratification in DTC Risk Group Stratification in DTC Low risk Good disease control Good survival Intermediate risk Moderate disease control Reasonable survival High risk Poor disease control Poor survival Intermediate risk Microscopic extrathyroidal extension Lymph node metastasis Aggressive histology Vascular invasion Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid

3 Regional Nodal Staging of DTC AJCC Staging in DTC Nx Regional lymph nodes cannot be assessed >45 years N0 N1 No regional lymph node metastasis Regional lymph node metastasis N1a Metastasis to level VI (pretracheal, paratracheal and prelaryngeal/delphian lymph nodes) N1b Metastasis to unilateral, bilateral or contralateral cervical or superior mediastinal lymph nodes Stage T N M I T1 N0 M0 II T2 N0 M0 III T3 N0 M0 T1-3 N1a M0 IVA T1-3 N1b M0 T4a all N M0 IVB T4b all N M0 IVB all T all N M1 Risk Group Stratification in DTC Risk of Recurrence Based on Nodal Status at Presentation Clinical N0 Range 0-9%, Mean 4% Clinical N0, Pathologic N1 by Elective ND Range %, Mean 6% Lymph Node Metastasis and Survival in DTC 20-year DSS Age Group N0 N1 <45 yrs 94% 100%* >45 yrs 90% 79% p = 0.06 Clinical N1, Pathologic N1 (clinically apparent) Range 10-42%, Men 22% Cranshaw, Surg Oncol 2008; Bardet, Eur J Endo 2008; So, Surgery 2010; Wada, Ann Surg Hughes et al Thyroid Lymphatics Regional Lymphatic Metastatic Routes Considerations Cross-communication of intraglandular lymphatics Extensive bilateral drainage High incidence of regional metastasis Multiple nodal groups at risk Lymphatic channels parallel venous drainage Inferior RLN nodes, paratracheal nodes anterior superior mediastinum Superior Prelaryngeal, pretracheal, paraglandular nodes low/mid/upper jugular nodes Lateral lower and midjugular nodes transverse cervical nodes Posterior RLN, paratracheal retropharyngeal, retroesophageal nodes

4 Overview Clinical Epidemiology in DTC Diagnostic Imaging and Biopsy Surgical Management of the Neck Central/ Recurrence Thyroid ATA Guidelines 2009 R21. Pre-op neck US for all patients undergoing surgery for a malignant FNA result to stage neck disease. B Moreno et al, Thyroid Cooper et al. Thyroid Negative findings predict excellent long-term regional control and survival Thyroid Other CT Iodine scanning Other CT Iodine scanning ATA Guidelines 2009 R22. Routine preoperative use of other imaging studies is not recommended. E Cooper et al. Thyroid Other CT Iodine scanning However US and CT have improved sensitivity and comparable specificity for nodal disease in thyroid cancer patients than either exam alone. Kim E. Thyroid 2008.

5 Other CT Iodine scanning CT or Lymph node metastasis Recurrent disease Vocal cord paralysis Fixation of mass Aerodigestive tract symptoms Other CT Iodine scanning No role in initial diagnosis of DTC (incidentalomas only) Low NPV, sensitivity, specificity in DTC Limited role in surveillance Deitlin 1997, Jadvar 1998, Feine 1998, Altenvoerde 1998, Chung 1999, Alnafasi 2000 Nodal Evaluation with FNA Overview US guidance Reduces non-diagnostic rate Diagnosis of papillary cancer is 99% accurate Use to formulate or change surgical plan Positive neck FNA Negative neck FNA Caveats: False negative rate = 1-6% Clinical Epidemiology in DTC Diagnostic Imaging and Biopsy Surgical Management of the Neck Central/ Recurrence Anatomy Levels VI and VII A paramedian bilateral compartment Defined: Carotid to carotid Cricoid to innominate Contains lymphovascular tissue, fat, thymus, parathyroid glands Anatomy Levels VI and VII A paramedian bilateral compartment Lymph Node Components Pre-cricoid laryngeal (Delphian) Paratracheal Retropharyngeal Retroesophageal Pretracheal

6 Metastasis Mean prevalence in DTC ~ 60% Independent risk factor for local recurrence Recurrence rates high for macroscopic (10-30%) but not microscopic LN disease ATA Consensus Summary Therapeutic CND implies that nodal metastasis is apparent clinically (preop or intraop) or by imaging (clinically N1a) R27a: Therapeutic CND for patients with clinically involved central or lateral neck nodes should accompany total thyroidectomy. B Bardet et al 2008 DL Steward. ATA Surgery Working Group. Thyroid ATA Consensus Summary Prophylactic (Elective) CND implies nodal metastasis is not detected clinically or by imaging (clinically N0). R27b: Prophylactic CND (ipsi or bilateral) may be performed in patients with PTC with clinically uninvolved central neck LNs for advanced tumors (T3/T4) C ATA Consensus Summary Prophylactic (Elective) CND implies nodal metastasis is not detected clinically or by imaging (clinically N0). R27c: Near-total or total thyroidectomy without prophylactic CND may be appropriate for small (T1/T2), non-invasive, clinically nodenegative PTCs and most follicular cancer. C DL Steward. ATA Surgery Working Group. Thyroid DL Steward. ATA Surgery Working Group. Thyroid ATA Consensus Summary Oncologic Goals in CND Clear all macro- and microscopic disease in the central neck Provide accurate postoperative staging that may guide treatment and surveillance Upstages 30-50% of pts >45 yrs ATA Consensus Summary Berry picking implies removal only of the clinically involved LNs rather than a complete nodal group within the compartment and is not recommended. Comprehensive Compartmental Dissection Hughes et al. Surgery DL Steward. ATA Surgery Working Group. Thyroid

7 Therapeutic Dissection Indications Right Advanced thyroid primary: T3 or T4a Advanced age Node positivity cn+, US+, USGFNA+ Advanced histologies Hurthle cell, Insular, cytopath features c/w poorly differentiated carcinoma ( spindle cells ) Anaplastic (IVA) Medullary carcinoma Left Routine CND Arguments in Favor High incidence of regional lymphatic spread in PTC Level VI metastasis local recurrence higher mortality CND decreases Tg levels and increases % of patients with undetectable Tg Safe procedure in experienced hands Scheumann 1994, Hughes 1996, Loh 1997, Noguchi 1998, Hay 1999, Sugitani 2004, Lundgren 2006, Doherty 2007 Routine CND Arguments Against Increased risk Conflicting recurrence & survival data LN metastases are not a factor in MACIS or AMES staging systems Elective CND morbidity correlates with surgeon experience and extent of dissection Most thyroid surgery not done by highvolume surgeons Overview Clinical Epidemiology in DTC Diagnostic Imaging and Biopsy Surgical Management of the Neck Central/ Recurrence

8 ATA Guidelines 2009 R28. Therapeutic lateral neck dissection should be performed for patients with biopsy proven metastatic lateral cervical lymphadenopathy. B ATA Consensus Review of the Anatomy, Terminology, and Rationale for Dissection in Differentiated Thyroid Cancers. Thyroid 2012;22(5): ATA Guidelines 2009 R28. Therapeutic lateral neck dissection should be performed for patients with biopsy proven metastatic lateral cervical lymphadenopathy. B Selective neck dissection of levels IIA, III, IV, and VB Routine prophylactic lateral neck dissection not proven to improve survival ATA Guidelines 2009 Biopsy any highly suspicious lymph node in the lateral neck without regard to size Comprehensive compartment-oriented neck dissection Revision cases: Focus upon levels of demonstrable recurrence appropriate for lateral neck Assumes prior LND ATA Consensus Review of the Anatomy, Terminology, and Rationale for Dissection in Differentiated Thyroid Cancers. Thyroid 2012;22(5): ATA Consensus Review of the Anatomy, Terminology, and Rationale for Dissection in Differentiated Thyroid Cancers. Thyroid 2012;22(5): Management Types of Neck Dissection Selective Lateral II, III, IV Anterior VI Comprehensive II, III, IV, V, VI Mediastinal VII Initial Management: cn+ patient Prove Disease: USgFNA Bx Stage neck: US and Total thyroidectomy with ipsilateral CND + LND Postoperative RAI T4 suppression therapy

9 Management Follow-Up Management: cn+ patient Surgical Risks Infection (<1%) Follow TG levels Surveillance iodine scan Surveillance neck US Suspicious Nodes USgFNA PET for non-iodine avid (I 131 -), Tg rising patients Lymphadenectomy for FNA+ disease Bleeding Chyle leakage Frozen shoulder syndrome Vascular injury Damage to major nervous structures Hypoglossal, Vagus, Phrenic, Brachial plexus Damage to cervical sensory and greater auricular nerves Therapy After Surgery Overview Hospital PT (shoulder exercises): Routine post-nd Calcium replacement or supplementation? Treatment of hypothyroidism Endocrinology Referral RAI: Post-operative scanning +/- therapy Serum Tg monitoring (with Tg Abs) TSH supression therapy: T3/T4 Clinical Epidemiology in DTC Diagnostic Imaging and Biopsy Surgical Management of the Neck Central/ Recurrence Surveillance US Thyroid bed, central + bilateral necks Avoiding Recurrence Management Tips Preoperative Imaging US; CT or if cn+ Complete thyroidectomy Leave no gross disease (R0-R1) Leave minimal residual thyroid tissue Carefully examine the paratracheal bed Do this in every case Therapeutic CND if nodes are detected Recurrence in DTC Pitfalls of Reoperation Nerve injury Failure to locate and remove disease Hypocalcemia Risk: 0-30% Permanent more common in reoperation Avoid superior parathyroid Parathyroid autotransplantation

10 Detection of Recurrence Summary Palpable neck mass Elevated Tg Surveillance Imaging US I 131 scan scan FNA Confirmation Systematic Preoperative Nodal Evaluation US with USgFNA Cross-sectional imaging to optimize surgical planning and identify metastatic disease in unusual locations Comprehensive Surgical Dissection Post-operative Therapy Re-operation ND Summary Summary Systematic Preoperative Nodal Evaluation Systematic Preoperative Nodal Evaluation Comprehensive Surgical Dissection Primary or recurrent DTC metastatic to neck Comprehensive Surgical Dissection Levels IIA-VB CND for N1a+, N1b+, high risk cn0 Post-operative Therapy Post-operative Therapy PT, LT4, Calcium, RAI, Surveillance imaging Re-operation ND Re-operation ND Summary Systematic Preoperative Nodal Evaluation Comprehensive Surgical Dissection Post-operative Therapy Re-operation ND Focused re-dissection