Thyroid Cancer Update: Nodules to Treatment Strategies

1. Update on Thyroid Cancer KY Chapter ACS Meeting September 8, 2017 Cortney Y. Lee, MD, FACS Associate Professor of Surgery Section of Endocrine Surgery

2. Objectives • Review the evaluation and management of thyroid nodules. • Discuss FNA diagnosis including Bethesda Criteria. • Summarize types of thyroid cancer including differences in treatment. • Explain the new diagnosis of NIFTP and how it affects treatment/management. • Describe the surgical management of thyroid cancer. • Compare the shift in use of radioactive iodine in lieu of recent ATA guidelines.

3. “Can the thyroid in the state of enlargement be removed? Emphatically experience answers no…every stroke of the knife will be followed by a torrent of blood and lucky will it be for him if his victim lives long enough for him to finish his horrid butchery. No honest and sensible surgeon would ever engage in it.” - Samuel Gross 1848

4. Father of Thyroid Surgery Emil Theodor Kocher (1841-1917) Nobel Prize 1909 Study of the thyroid

5. Another nodule?!!! Thyroid nodules

6. Thyroid disease • 30 million Americans with thyroid problems • 15 million Synthroid scripts written annually • 1 of 10 women has a thyroid nodule • 60% women have a nodule by 60 yo • Abnormalities found on exam or incidentally on imaging • ATA guidelines on thyroid nodules and differentiated thyroid cancer • Search “ATA guidelines” 2

7. What if I find a nodule? • TSH • If normal/high, proceed with US/FNA • If low, nuclear uptake scan (only indication) • ULTRASOUND is best imaging test • FNAif indicated • ATA 2015 guidelines

8. 1 cm 1.5 cm 2 cm No FNA 2015 ATA Thyroid Nodule/DTC Guidelines

9. 2009 ATA Guidelines for Nodules

10. 2015 ATA Guidelines for Nodules

11. US Size FNA 2015 ATA Thyroid Nodule/DTC Guidelines

12. Thyroid Nodule Cliff Notes • Workup: TSH, US, FNA • Uptake scan is ONLY for hyperthyroidism • FNA criteria for nodules • Solid ~1.0 to1.5 cm • Complex/Spongiform ~ 2 cm • Simple cysts – no FNA

13. What is “Bethesda”? Thyroid FNA

14. Fine Needle Aspiration) • Office procedure with ultrasound guidance • Must get an adequate sample • 6 groups of at least 10 cells each • 2 passes minimum • Immediate cytopathology helps adequacy • Once adequate, three possible answers: • Benign (Bethesda II) • Malignant (Bethesda VI) • Indeterminant (Bethesda III, IV, V)

15. Benign Indeterminant Malignant Chance of cancer ≤3% Chance of cancer 5-75% Chance of cancer ≥97% Repeat US Surgery Repeat FNA (+/- genetic classifier) OR surgery Total (vs. lobe) +/- lymph nodes Stable Growth If surgery, lobe. If benign, follow. No f/u Repeat FNA

16. Key words in FNA reports • Adequate • “No malignancy” • Drying artifact • Obscured by blood • Paucicellular • Follicular cells • Hurthle cells • Lymphocytes • Macrofollicles • Macrophages • Thin colloid • Cellular • Cytologic atypia • Microfollicles • Nuclear grooves • Intranuclear inclusions • Thick colloid

17. Common descriptions • Benign – bland follicular cells, abundant colloid, macrophages, Hurthle cell change • Hashimoto’s – lymphocytes, Hurthle cells • Follicular/Hurthle cell nodules – cellular with predominantly follicular or Hurthle cells, microfollicles, little to no colloid • Papillary – Nuclear grooves, intranuclear inclusions, powdery chromatin

18. Algorithm for FNA result 6 Bethesda Categories 2015 ATA Thyroid Nodule/DTC Guidelines

19. Bethesda Categories The Bethesda System for Reporting Thyroid Cytopathology. ES Cibas, SZ Ali. Thyroid. Nov 2009, 19(11):1159-1165. 2015 ATA Thyroid Nodule/DTC Guidelines

20. Bethesda Categories Molecular/Genetic Testing The Bethesda System for Reporting Thyroid Cytopathology. ES Cibas, SZ Ali. Thyroid. Nov 2009, 19(11):1159-1165.

21. Gene Expression (i.e. Afirma) • Designed to assist in the indeterminate categories (mainly Bethesda III and IV) • Classifies indeterminate as: • Benign = <6% risk of malignancy • Suspicious = ~40% risk of malignancy • Use to avoid unnecessary surgery • Afirma suspicious ≠ cancer

23. FNA Cliff Notes • Assure adequacy • Request Bethesda classification by your pathologists • Follicular neoplasm ≠ cancer • Genetic/molecular tests can help

24. “If you had to pick a cancer…” Thyroid cancer

25. Rising incidence of thyroid cancer • Increased incidental findings (imaging) • Significant cancers are also increasing • Mortality is stable

26. Thyroid Cancer • Papillary, Follicular, Hurthle cell, Medullary, Anaplastic • Surgery ideal for all • RAI used postoperatively in some • Pregnancy– surgery can usually be delayed until after delivery • Can observe very small cancers in poor surgical candidates

27. Types of thyroid cancer *Survival data from Mayo Clinic 1940-1990

28. TNM for Thyroid Cancer T Categories N Categories Nx Nodes not assessed N0 Nodes negative N1a Central nodes (VI) N1b Lateral nodes (II-V, VII) • Tx Not assessed • T0 No evidence of 1° • T1a ≤ 1 cm • T1b 1-2 cm • T2 2-4 cm • T3 >4 or minimal ETE • T4a gross ETE • T4b invading spine or major vessels (arteries) • All anaplastic T4a or T4b M Categories • Mx Not assessed • M0 No distant mets • M1 Distant mets 2015 ATA Thyroid Nodule/DTC Guidelines

29. Staging for PTC & FTC * The staging system will change in January 2018 (one change is age to 55) 2015 ATA Thyroid Nodule/DTC Guidelines

30. Factors that influence prognosis • Age (40yo for men, 50yo for women) • Size of primary • Extrathyroidal invasion • Aggressive variants (tall cell, columnar) • Extent of nodal metastases • Distant mets • Sex (questionably worse for men)

31. New Diagnosis: NIFTP • NIFTP= Noninvasive follicular thyroid neoplasm with papillary-like nuclear features • Previously classified as FVPTC

32. “Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma”. YE Nikiforov, et al. JAMA Oncol. 2016 Aug 1; 2(8): 1023-1029.

33. “Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma”. YE Nikiforov, et al. JAMA Oncol. 2016 Aug 1; 2(8): 1023-1029.

34. How does NIFTP change things? • Changes surgical management • No need for completion or RAI • Patient DOES need follow up (like a cancer) • Risk % of malignancy in Bethesda will change • Affects utility of molecular/genetic tests

35. Cancer Cliff Notes • Papillary is most common and has best prognosis • Follicular and Hurthle cell cancers CANNOT be diagnosed on FNA– only on final pathology • New NIFTP is not cancer, but not benign • Medullary pts need genetic evaluation

36. What changes with cancer? Surgery for cancer

37. Surgical Options • Total (or near-total) thyroidectomy • No role for subtotal thyroidectomy • Small PTC/FTC can be treated with lobectomy • If known nodal involvement, entire compartment should be addressed • Central (VI) vs. Lateral (II-V) • Prophylactic central node dissection • Pro: staging, could change treatment; decrease need for future central neck surgery • Con: more risk to parathyroids, higher risk of temporary hypoparathyroidism, doesn’t change outcome

38. Nodal Basins • Imperative to perform detailed US of nodal basins (II-VI) preoperatively • Can change surgical decision making • Anatomic compartment dissections • Not “berry picking”

39. It’s out. Now what? Postsurgical treatment & follow up

40. How do we follow thyroid cancer? • Thyroglobulin (Tg) • Made by normal thyroid and most thyroid cancers • Used as a tumor marker after resection of tumor • Not used to diagnosis cancer prior to surgery • US • Nodes • Remaining thyroid (if applicable)

41. TSH Suppression • Thyroid hormone suppresses cancer • Goal TSH • Low risk, Tg <0.2 TSH 0.5-2.0 • Low risk, Tg >0.2 TSH 0.1-0.5 • Intermediate risk TSH 0.1-0.5 • High risk TSH <0.1 • If excellent response to therapy, TSH up to 0.1-0.5

42. Why give radioactive iodine? • Primary goal: ablation of thyroid remnant • Recommended ablative dose of 30-50 mCi • Can also treat non-imagable micrometastases • Can be therapeutic • Need higher dose (100+ mCi) • Given 1-2 months after surgery • Low iodine diet for 2 weeks prior to treatment • Must elevate TSH prior to treatment

43. Two methods of TSH elevation • Hormone withdrawal • Patient stops short-acting thyroid hormone 2 weeks prior to treatment • Cheap, effective, miserable • Thyrogen (recombinant human TSH) • Shots for a few days prior to treatment • Expensive, but avoids swing in hormone levels (less life-altering)

44. Who needs RAI? 2015 ATA Thyroid Nodule/DTC Guidelines

46. (continued)

47. Who needs RAI? • Clearly indicated in large cancers (>4cm) and cancers with aggressive features, invasion or lateral nodal mets • Not indicated in cancers ≤ 1cm • Clear benefit not demonstrated in most cancers <4 cm without suspicious features or nodal involvement

48. Changes in recommendations • Indication for RAI is decreasing • Less need for RAI changes surgical planning • Lobectomy may be a viable option in low-risk cancers • Requires a change in our standard treatment and follow up of thyroid cancer • Ongoing evolution

49. Cut-throat surgeons… Why surgery?!

50. Thyroid Surgery • Outpatient surgery (or overnight) • Incisions much smaller than in past • Recovery • ~1 week off work • No restrictions (except for driving for 4-5 days) • Low risk in experienced hands (temp, permanent) • Voice – injury to recurrent laryngeal nerve (<5%, <1%) • Hypocalcemia – injury to parathyroids (10-15%, 2-5%) • Post op hematoma (<1%)