Surgical Management of Differentiated Thyroid Cancer: Update on 2015 ATA Guidelines Gerard M. Doherty, MD Chair of Surgery Utley Professor of Surgery and Medicine Boston University Surgeon-in-Chief Boston Medical Center Disclosures Gerard Doherty UCSF Postgraduate Course in Endocrine and Breast Surgery No financial relationships to disclose I will not discuss off-label or investigational use in my presentation ATA DTC Consensus Guidelines Risk-adapted Management Traditional Paradigm One Size Fits All 60 50 Recurrence Total thyroidectomy RAI remnant ablation TSH Suppression Unified follow up plan Risk Adapted Paradigm Individualized risk assessment 40 Percent 30 20 What Risks? Death Recurrence Persistence Failing initial therapy Preoperative imaging Tailored operation Selective RAI use Risk-based TSH suppression and follow-up 10 0 Death 0 5-9 10-19 2 20-29 30-39 4 40-49 50-59 6 60-69 >70 Age (yrs) at time of initial therapy Mazzaferri EL, Kloos RT. J Clin Endocrinol Metab. 2001;86(4):1447-1463. 1
Risk-adapted Management ATA Update - Estimating Risk of Recurrence Low Risk Classic PTC No local or distant mets N0 or <5 node micromets Complete resection No tumor invasion No vascular invasion If given, no RAI uptake outside thyroid bed Intermediate Risk Microscopic ETE Gross node mets or >5 micromets Aggressive Histology Vascular invasion High Risk Macroscopic gross ETE Incomplete tumor resection Node met > 3 cm Distant Mets Inappropriate Tg elevation Risk of Structural Disease Recurrence (In patients without structurally identifiable disease after initial therapy) High Risk Gross extrathyroidal extension, incomplete tumor resection, distant metastases, or lymph node >3 cm Intermediate Risk Aggressive histology, minor extrathyroidal extension, vascular invasion, or > 5 involved lymph nodes (0.2-3 cm) Low Risk Intrathyroidal DTC 5 LN micrometastases (< 0.2 cm) FTC, extensive vascular invasion ( 30-55%) pt4a gross ETE ( 30-40%) rmt1 pn1 with extranodal extension, >3 LN involved ( 40%) PTC, > 1 cm, TERT mutated ± BRAF mutated* (>40%) pn1, any LN > 3 cm ( 30%) PTC, extrathyroidal, BRAF mutated*( 10-40%) PTC, vascular invasion ( 15-30%) Clinical N1 ( 20%) pn1, > 5 LN involved ( 20%) Intrathyroidal PTC, < 4 cm, BRAF mutated* ( 10%) pt3 minor ETE ( 3-8%) pn1, all LN < 0.2 cm ( 5%) pn1, 5 LN involved ( 5%) Intrathyroidal PTC, 2-4 cm ( 5%) Multifocal PMC ( 4-6%) pn1 with extranodal extension, 3 LN involved (2%) Minimally invasive FTC ( 2-3%) Intrathyroidal, < 4 cm, BRAF wild type* ( 1-2%) Intrathyroidal unifocal PMC, BRAF mutated*, ( 1-2%) Intrathyroidal, encapsulated, FV-PTC ( 1-2%) Unifocal PMC ( 1-2%) Initial Surgery A) For patients with thyroid cancer >4 cm, or with gross extrathyroidal extension (clinical T4), or clinically apparent metastatic disease to nodes (clinical N1) or distant sites (clinical M1), the initial surgical procedure should include a near-total or total thyroidectomy and gross removal of all primary tumor unless there are contraindications to this procedure. (Strong Recommendation, Moderate-quality evidence) B) For patients with thyroid cancer >1 cm and <4 cm without extrathyroidal extension, and without clinical evidence of any lymph node metastases (cn0), the initial surgical procedure can be either a bilateral procedure (near-total or total thyroidectomy) or a unilateral procedure (lobectomy). Thyroid lobectomy alone may be sufficient initial treatment for low risk papillary and follicular carcinomas; however, the treatment team may choose total thyroidectomy to enable RAI therapy or to enhance follow-up based upon disease features and/or patient preferences. (Strong Recommendation, Moderatequality evidence) C) If surgery is chosen for patients with thyroid cancer <1 cm without extrathyroidal extension and cn0, the initial surgical procedure should be a thyroid lobectomy unless there are clear indications to remove the contralateral lobe. Thyroid lobectomy alone is sufficient treatment for small, unifocal, intrathyroidal carcinomas in the absence of prior head and neck irradiation, familial thyroid carcinoma, or clinically detectable cervical nodal metastases. Initial Surgery C) If surgery is chosen for patients with A) For patients with thyroid cancer >4 cm, or with gross extrathyroidal extension (clinical T4), or clinically apparent metastatic disease to nodes (clinical N1) or distant sites (clinical M1), the thyroid initial surgical cancer procedure <1 should cm include without a near-total or total thyroidectomy and gross removal of all primary tumor unless there are contraindications to this procedure. (Strong Recommendation, Moderate-quality evidence) extrathyroidal extension and cn0, the initial surgical procedure should be a B) For patients with thyroid cancer >1 cm and <4 cm without extrathyroidal extension, and without clinical evidence of any lymph node metastases (cn0), the initial surgical procedure thyroid can be either lobectomy a bilateral procedure unless (near-total there or total are thyroidectomy) clear or a unilateral procedure (lobectomy). Thyroid lobectomy alone may be sufficient initial treatment indications for low risk papillary to remove and follicular the carcinomas; contralateral however, the treatment team may choose total thyroidectomy to enable RAI therapy or to enhance follow-up based upon disease lobe. features and/or patient preferences. (Strong Recommendation, Moderatequality evidence) C) If surgery is chosen for patients with thyroid cancer <1 cm without extrathyroidal extension and cn0, the initial surgical procedure should be a thyroid lobectomy unless there are clear indications to remove the contralateral lobe. Thyroid lobectomy alone is sufficient treatment for small, unifocal, intrathyroidal carcinomas in the absence of prior head and neck irradiation, familial thyroid carcinoma, or clinically detectable cervical nodal metastases. 2
Slide 6 rmt1 This "approximately 40%" was previously "38%". so I made it approximately 40% to make it seem less precise tuttler, 4/13/2014
Initial Surgery A) For patients with thyroid cancer >4 cm, A) For patients with thyroid cancer >4 cm, or with gross extrathyroidal extension (clinical T4), or clinically apparent metastatic disease to nodes (clinical N1) or distant sites (clinical M1), the or initial with surgical gross procedure extrathyroidal should include a near-total extension or total thyroidectomy and gross removal of all primary tumor unless there are contraindications to this procedure. (Strong Recommendation, Moderate-quality evidence) (clinical T4), or clinically apparent metastatic disease to nodes (clinical N1) or B) For patients with thyroid cancer >1 cm and <4 cm without extrathyroidal extension, and without clinical evidence of any lymph node metastases (cn0), the initial surgical procedure distant can be either sites a bilateral (clinical procedure M1), (near-total the or total initial thyroidectomy) or a unilateral procedure (lobectomy). Thyroid lobectomy alone may be sufficient initial treatment surgical for low risk procedure papillary and follicular should carcinomas; include however, a the neartotal disease features or total and/or patient thyroidectomy preferences. (Strong and Recommendation, gross Moderate- treatment team may choose total thyroidectomy to enable RAI therapy or to enhance follow-up based upon quality evidence) removal of all primary tumor unless there are contraindications to this procedure. C) If surgery is chosen for patients with thyroid cancer <1 cm without extrathyroidal extension and cn0, the initial surgical procedure should be a thyroid lobectomy unless there are clear indications to remove the contralateral lobe. Thyroid lobectomy alone is sufficient treatment for small, unifocal, intrathyroidal carcinomas in the absence of prior head and neck irradiation, familial thyroid carcinoma, or clinically detectable cervical nodal metastases. Initial Surgery B) For patients with thyroid cancer >1 cm and <4 A) For patients with thyroid cancer >4 cm, or with gross extrathyroidal extension (clinical T4), or cm clinically without apparent extrathyroidal metastatic disease to nodes extension, (clinical N1) and or distant without sites (clinical M1), the initial surgical procedure should include a near-total or total thyroidectomy and gross clinical removal of all evidence primary tumor of unless any there lymph are contraindications node metastases to this procedure. (Strong Recommendation, Moderate-quality evidence) (cn0), the initial surgical procedure can be either a bilateral procedure (near-total or total B) For patients with thyroid cancer >1 cm and <4 cm without extrathyroidal extension, and without clinical evidence of any lymph node metastases (cn0), the initial surgical procedure thyroidectomy) can be either a bilateral or procedure a unilateral (near-total procedure or total thyroidectomy) or a unilateral procedure (lobectomy). Thyroid lobectomy alone may be sufficient initial treatment (lobectomy). for low risk papillary Thyroid and follicular lobectomy carcinomas; alone however, may the treatment be team may choose total thyroidectomy to enable RAI therapy or to enhance follow-up based upon disease sufficient features initial and/or patient treatment preferences. for (Strong low Recommendation, risk papillary Moderatequality evidence) and follicular carcinomas; however, the treatment team may choose total thyroidectomy to enable C) If surgery is chosen for patients with thyroid cancer <1 cm without extrathyroidal extension and cn0, the initial surgical procedure should be a thyroid lobectomy unless there are RAI clear therapy indications to or remove to enhance the contralateral follow-up lobe. Thyroid based lobectomy upon alone is sufficient treatment for small, unifocal, intrathyroidal carcinomas in the absence of prior head and disease neck irradiation, features familial and/or thyroid patient carcinoma, or preferences. clinically detectable cervical nodal metastases. 1088 Thyroid lobectomies for PTC Factors affecting change Recent on lobectomy Reevaluation of Bilimoria NCDB Decreased routine RAI use Improved ultrasound exams both pre and post treatment Experience with thyroglobulin follow-up after lobectomy Matsuzu World J Surg 2014 3
Lymph node metastases Thyroid cancer survival by Age and Palpable Lymphadenopathy Nodal metastases long believed important for locoregional recurrence but not survival Large studies did not show nodal metastases as important to survival (Cady, Hay, Degroot) Newer show nodes can be important predictors extent of node involvement in predicting recurrence Survival rates 100 80 60 40 20 0 Older with PLA (n=19) Younger with PLA (n=11) P: not calculated 0 60 120 150 240 (M) Time Younger without PLA (n=67) Older without PLA (n=134) Wada N, et al. Eur J Surg Oncol. 2008;34(2):202-207. SEER Database Assessment 1988 2003; sampled about 26% of US population 40034 patients 33088 with complete and no XRT 30054 Papillary or FVPTC 2584 Follicular PTC Survival by Age and Node Status Zaydfudim et al, Surgery 2008 Zaydfudim et al, Surgery 2008 4
Pathologic N1 Status Recurrence Risk Stratification Will Rogers Phenomenon Characteristic Median Recurrence Rate Range of Recurrence Rate Clinical N0 2% 0-9% < 5 metastatic nodes 4% 3-8% > 5 metastatic nodes 19% 7-21% Clinical N1 22% 10-42% Clinical N1 with extranodal extension 24% 15-32% ATA Surgical Affairs Committee. Thyroid 2012 When the Okies left Oklahoma and moved to California, they raised the average intelligence level in both states. Feinstein AR NEJM 1985 Will Rogers Current node paradigm Lymph node status is important in DTC Reveals biology of disease Size and number of nodes important Prognosis Recurrence Survival Can we alter the course of disease with riskbased therapy? No controversy regarding the value of therapeutic central neck node dissection Key Points Prophylactic central neck node dissection may be useful in light of some patient characteristics (higher risk) or impact on treatment decisions 5
Proposed Guidelines ATA Rec 36 Variation in Utilization of RAI for Thyroid Cancer 100 A) Therapeutic central-compartment (level VI) neck dissection for patients with clinically involved central nodes should accompany total thyroidectomy to provide clearance of disease from the central neck. B) Prophylactic central-compartment neck dissection (ipsilateral or bilateral) should be considered in patients with papillary thyroid carcinoma with clinically uninvolved central neck lymph nodes (cn0) who have advanced primary tumors (T3 or T4), clinically involved lateral neck nodes (cn1b), or if the information will be used to plan further steps in therapy. Estimated Probability (%) of Receiving RAI for Low Risk PTC 80 60 40 20 C) Thyroidectomy without prophylactic central neck dissection may be appropriate for small (T1 or T2), noninvasive, clinically nodenegative PTC (cn0) and for most follicular cancer. Haymart MR, JAMA Aug 2011 1 100 200 300 400 Hospital Rank Probability of Receiving RAI for Low Risk PTC ATA recurrence risk ATA low risk T1a N0,Nx Tumor size 1cm RAI Improves Disease- Specific Survival? RAI Improves Disease- Free Survival? Post-Surgical RAI Indicated? No No No Key Points RAI Risk- Adapted Management ATA low risk T1b,T2 N0, Nx ATA low to intermediate risk T3 N0,Nx ATA low to intermediate risk T3 N0,Nx ATA low to intermediate risk T1-3 N1a ATA low to intermediate risk T1-3 N1b ATA high risk T4 Any N Any M ATA high risk M1 Any T Any N Tumor size 1-4 cm Tumor size >4 cm Microscopic ETE, any tumor size Level 6 lymph node metastases Lateral neck or mediastinal lymph node metastases Gross extrathyroidal extension Distant metastases No No No, except possibly in subgroup of patients 45 years of age No, except possibly in subgroup of patients 45 years of age Not routine consider with aggressive histology or vascular invasion (ATA intermediate risk) Consider Consider Consider Consider More risk-based judgment on extent of primary treatment Less routine radioiodine treatment Selective use of prophylactic central neck dissection unchanged 6
Central neck dissection Boston University Medical Campus http://www.bumc.bu.edu/surgery/ 7