Guidelines for the Management of Differentiated Thyroid Cancer Nancy D. Perrier, MD, FACS Professor of Surgery Chief, Section of Surgical Endocrinology Department of Surgical Oncology M.D. Anderson Cancer Center Houston, Texas
Papillary Thyroid Cancer Current Controversy • Increased awareness of the incidence of neck • recurrence causing physical and emotional patient • distress • Improved ability to detect neck recurrence: • transcutaneous US and stimulated Tg • Greater sensitivity of US and Thyroglobulin (Tg) • Diagnosis of sub-cm neck recurrence of ? clinical • significance
Aims: • Discuss Incidence of Differentiated Thyroid Cancer • Review the Staging System • Become aware of the 2009 Management Guidelines • Review: Treatment Extent of Surgical Resection Role of Radioactive Iodine Ablation Long – Term Follow Up
Age at Diagnosis: Differentiated Thyroid Cancer 400 350 Papillary 300 250 Follicular No. patients 200 150 100 50 0 20-29 10-19 30-39 50-59 80-90 <10 40-49 60-69 70-79 Age at time of diagnosis (yr) Ohio State Study 1,355 Patients Mazzaferri EL. Am J Med. 1994;97:418–428. Median ages (yr): papillary 32.0; follicular 36.5. 929 (69%) females; 426 (31%) males.
40 30 Recurrence 20 Cancer death Cumulative percent 10 0 0 10 20 30 40 Years after initial therapy Outcome: Differentiated Thyroid Ca A Mandate for Lifelong Follow up Outcome: Cumulative % Recurrence& Cancer Death After Initial Therapy Mazzaferri EL. Am J Med 1994; 97:418-428.
Under Age 45 Stage I M0 Stage II M1 Age > 45 Stage I T1N0 Stage II T2N0 Stage III T3 or N1a Stage IVA T4a or N1b Stage IVB T4b Stage IVC M1 AJCC Staging Manual (6th ed)Papillary/Follicular T1 < 2 cm T2 2 - 4 cm T3 > 4 cm or extrathyroidal T4a adjacent structures T4b vertebral fascia,vessels N1a level VI N1b all others M0 No distant mets M1 Distant mets 2002
“Levels of Evidence”: ATA Guidelines U.S. Preventive Services Task Force , Agency for Healthcare Research & Quality
Treatment and Management ofThyroid Cancer • Preoperative Workup • Primary Treatment • Adjuvant Treatment • Long Term Monitoring
Adjuvant Treatment Radioiodine TSH-suppressive thyroid hormone therapy Long term Monitoring Ultrasonography Serum Thyroglobulin Whole-body 131I scanning PET Preoperative Workup Ultrasonography FNA Laboratory Tests TSH ( no Tg or Calcitonin) Primary Treatment Thyroidectomy Lymph Node Resection Treatment and Management ofThyroid Cancer Cooper, DS. Thyroid Volume 19, Nov 2009
ATA Guidelines:Preoperative Assessment of Thyroid Ca • Ultrasonography • Entire thyroid gland including contralateral lobe • Cervical lymph nodes- central and bilateral (Recommendation B) • No Thyroglobulin (Recommendation E: fair evid no improve) • No Calcitonin (Recommendation I: insufficient evidence) NCCN, Practice Guidelines in Oncology v.1.2007
Preoperative Ultrasound / Thyroid Ca N= 212 US (+) / PE (-) = 82 (39%) N = 61 N = 151 MTC = 26 (43%) DTC = 52 (34%) Operative strategy changed • Neck Dissection • Central = 32 • Ipsilateral = 21 • Contralateral = 9 • Neck Dissection • Central = 22 • Ipsilateral = 8 • Contralateral = 2 Kouvaraki MA. Role of preoperative ultrasonography in the surgical management of patients with thyroid cancer. Surgery 2003;134:946-954.
Cervical Recurrences = 9 (6%) Group 1 = 5 (6%) Group 2 = 0 Group 3 = 4 (8%) N = 207 Follow-up = 3 yrs DTC = 149 MTC = 58 Follow-up < 1 yr = 33 NED = 124 (83%) AWD = 14 (9%) DOD = 6 (4%) DOC = 5 (3%) Kouvaraki MA. Role of preoperative ultrasonography in the surgical management of patients with thyroid cancer. Surgery 2003;134:946-954.
Role of Preoperative Ultrasonography in Detecting LN Disease • Differentiated Thyroid Cancer involves cervical lymph nodes in 20-50% of patients • Frequency of micrometastasis may approach 90% depending on sensitivity of the detection method • Ultrasonography changed surgical paradigm in 39% cases Chow, SM. Cancer 2003;98:31-40 Qubain SW. Surgery 2002;131:249-56 Kouvaraki, MA. Surgery 2003;134:946-954
Adjuvant Treatment Radioiodine TSH-suppressive thyroid hormone therapy Long term Monitoring Ultrasonography Serum Thyroglobulin Whole-body 131I scanning PET Preoperative Workup Ultrasonography Thyroid Cervical Nodes FNA Laboratory Tests Primary Treatment Thyroidectomy Lymph Node Resection Treatment and Management ofThyroid Cancer Cooper, DS et al . Thyroid 2006;16:1-33
Surgical Intervention:2009 ATA Guidelines Recommendation A : Good Evidence “For patients with thyroid cancer > 1 cm, the initial surgical procedure should be a near- total or total thyroidectomy. Thyroid lobectomy alone may be sufficient for small, low risk, isolated, intrathyroidal papillary carcinomas in the absence of cervical LND or prior head and neck irradiation.”
Surgical Intervention:2009 ATA Guidelines “ Therapeutic central-compartment (level VI) neck is recommended for patients with clinically involved LN (Rec B- fair evid) “ProphylacticCLND may be performed in pts with T3 or T4 PTC tumors and uninvolved CLN disease (Rec C- exp opin) “No prophylactic CLND may be appropriate for small T1, T2 noninvasive clinically node negative and most follicular cancers. (Rec C- exp onin)
Total Thyroidectomy + Central Lymph Node Dissection • Will result in stage migration • Up to 40% of T1 tumors with (-) US may be N1a if the ipsilateral level VI nodes removed • May increase the number of patients receiving RAI • May increase the number of patients with negative total body scans Bonnet, et al. JCEM 2009;94:1162; Hughes, Doherty et al. Surgery Dec 2010; 148 (6) .
Level VI Cranial- superior thyroidal artery Caudal- innominate vein Lateral- carotid sheath Dorsal-prevertebral fascia Medial-border of contralateral thymus Central Neck Dissection Compliments of Sywak, M.
Central Lymph Node Dissection (Level VI)
Study Population (Dec 1995 - April 2005) 594 PTC (>1cm) 147 Clinical N+ 447 Clinical N0 Group A Total Thyroidectomy +Central LND (N=56) Group B Total Thyroidectomy (N = 391)
Group A: Total Thyroidectomy + CND • Mean nodal yield 5.3 • Positive nodes (H&E) 21/56 (38%)
Stimulated Serum Thyroglobulin (6-12 month) Group B: TT alone Group A : TT + CND 72%* 43%* *p=0.001
Well Differentiated Thyroid Carcinoma: Therapeutic vs. Elective Neck Dissection • Total Thyroidectomy • Ipsilateral Central Neck Dissection (Level VI) • Lateral neck dissection if biopsy proven metastatic lateral lymph node disease is • present
Preoperative Workup Ultrasonography Thyroid Cervical Nodes FNA Thyroid Function Tests Primary Treatment Thyroidectomy Lymph Node Resection Adjuvant Treatment Radioactive iodine TSH-suppressive thyroid hormone therapy Long term Monitoring Ultrasonography Serum Thyroglobulin Whole-body 131I scanning PET Treatment and Management ofWell Differentiated Thyroid Cancer
Papillary Carcinoma of the ThyroidRecurrence: AMES low-risk at Mayo Remnant 11% Distant 18% Non Remnant 14% Nodes 57% Hay, Surgery 1998;124:958. N = 1,656, 1940-1991
Role of Radioactive Iodine Ablation In Low Risk Patients (20 yr f/u) Hay, et al. 2002 MACIS < 6, 1970-2000
Role of Postoperative RAI Therapy • Ablation: Metastases, extra-thyroidal extension, primary tumor > 4 cm • Selective: 1-4 cm primary tumor, LN mets intermediate histology • Not recommended: < 1 cm or multifocal disease with all foci < 1 cm
Role of Postoperative RAI Therapy • Stage IV: Definitely • Stage III: Definitely • Stage II: Probably (all > 45 y) • Stage I: • Positive Nodes • Positive Invasive • Age > 45 • Vascular Invasion (Rec B) • TSH > 30 mU/L • After withdrawal or rhTSH • Post therapy scan 5-8 days after ablation Maybe, probably not Cooper, DS. Thyroid 2009; Vol 19
Highpoints of RAI Ablation • Thyroxin withdrawal or rhTSH stimulation • TSH > 30 mU/L • Iodine free diet for 2-3 weeks • Pre therapy scan may be useful if thyroid remnant cannot be ascertained • No residual disease: 30-100 mCi I 131 • Residual disease: 100-200 mCi I 131 • Posts treatment scan 5-8 days after I 131
Adjuvant therapy for DTC with rhTSH* < Age 45 T2-3 N0; T1-3 N1a ≥ Age 45 T1-2 N0 Excludes patients with incidental PTC of any age and T1N0 PTC in patients <45 years † MD discussion with nuclear medicine/endocrinologist on day 3 prior to ablative dose. Recommend no ablative dose if dxWBS is negative and serum Tg < 2 ng/mL ‡ Low-iodine diet starts 2 weeks prior to Day 1 rhTSH
Low Risk Target TSH 0 .1-0.5 mU/L Consider normalization as patient remains disease free High Risk Target TSH <0.1 mU/L Consider less aggressive therapy as patients ages (Rec B) Degree of TSH Suppression
Adjuvant Treatment Radioiodine TSH-suppressive thyroid hormone therapy Long term Monitoring Ultrasonography Serum Thyroglobulin Whole-body 131I scanning PET Preoperative Workup Ultrasonography Thyroid Cervical Nodes FNA Thyroid Function Tests Primary Treatment Thyroidectomy Lymph Node Resection Treatment and Management ofThyroid Cancer
Utility of Serum Thyroglobulin Measurements • Recommendation A: Good Evidence • “ Serum thyroglobulin should be measured every 6-12 months……using the same assay calibrated against a standard …......during follow-up of patients with DTC who have undergone total or near-total thyroidectomy and thyroid remnant ablation. • Antibodies should be assessed with every Tg” .
12 Month Follow Up • T1-2, N0-1 1) US 2) TSH Stimulated Tg and Tg antibodies 3) TSH stimulated Dx WBS scan • T3-4, detectable Tg or distant mets: RAI scan every 12 months until no response is seen to RAI treatment in iodine avid tumors NCCN 2009
Long Term Monitoring: ATA Guidelines • Thyroglobulin and anti-thyroglobulin antibodies: • Check Tg + abs every 6-12 months • TSH stimulated Tg ( withdrawal or rhTSH stim) measured 12 months after ablation. Subsequent testing ? • Neck Ultrasound: • 6 & 12 months, then annually for at least 3-5 years. LN > 5-8 mm should be bx for cytology, Tg and needle washout • RAI scan: • Low risk patient, negative ultrasound and negative TSH-stim Tg- No WBS after first scan following ablation • Others: Maybe scan, using low dose I 131 (Rec C: exp opin) Cooper, DS. Thyroid 2009 Nov , Vol 19
Conclusion • Preoperative ultrasonography helps to detect clinically occult lymph node disease • Standard techniques of total thyroidectomy plus ipsilateral central lymph node resectionminimizes cervical recurrences • RAI plays role of Stage 2, 3 ,4 disease. • TSH suppression is beneficial, degree depends on • risk assessment
Conclusions • End point for assessment of therapy in M0 patients is neck recurrence (not survival) • Therapeutic neck dissection should be • compartment oriented • Elective dissection of the ipsilateral paratracheal region (central neck) is the current controversy in surgery • All but the highest risk patients will have a dominant pattern of failure (neck) the treatment of which is surgery . Hold back on RAI please
Surgical Endocrinology THYROID ENDOCRINE PANCREAS PARA THYROID ADRENAL