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

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.

“Can the thyroid in the state of enlargement be removed “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

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

Another nodule?!!! Thyroid nodules

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

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

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

2009 ATA Guidelines for Nodules

2015 ATA Guidelines for Nodules

US Size FNA 2015 ATA Thyroid Nodule/DTC Guidelines

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

What is “Bethesda”? Thyroid FNA

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)

Repeat FNA (+/- genetic classifier) OR surgery 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

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 Unfortunately, not all pathologists use the Bethesda categories, which can make interpretation difficult.

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

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

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

Bethesda Categories Molecular/Genetic Testing Category % cancer Recommendation I Nondiagnostic 1-4% Repeat FNA II Benign 0-3% US follow up III AUS/FLUS 5-15% IV Follicular neoplasm/Suspicious for follicular neoplasm 15-30% Surgery (lobe) V Suspicious for malignancy 60-75% Surgery (lobe vs. total) VI Malignant 97-99% Surgery (likely total) Molecular/Genetic Testing Discuss follicular and hurthle cell cancer– about diagnosis (invasion, etc) The Bethesda System for Reporting Thyroid Cytopathology. ES Cibas, SZ Ali. Thyroid. Nov 2009, 19(11):1159-1165.

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

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

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

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

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 Mention that Hurthle cell = oncocytic and that Hurthle is a variant of follicular

Types of thyroid cancer Diagnosis on FNA? RAI avid? Prognosis 10yr / 20 yr survival (%)* Papillary Yes Best 95.5 / 94.7 Follicular No Most (2/3) 80.5 / 71.1 Hurthle Some (1/3) 84.4 / 78.7 Medullary Yes (occ.) None 82.9 / 79.7 Anaplastic Usually not needed Worst Fatal For benign FNAs– if susp US features, repeat US/FNA in 1 year. If low/intermediate– repeat US in 1-2 years. If very low risk, maybe never but if so >2 years. When repeating FNAs, some say wait 3 months, but it’s not been shown that waiting that long is necessary to get a better answer. *Survival data from Mayo Clinic 1940-1990

TNM for Thyroid Cancer T Categories N Categories 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 Nx Nodes not assessed N0 Nodes negative N1a Central nodes (VI) N1b Lateral nodes (II-V, VII) M Categories Mx Not assessed M0 No distant mets M1 Distant mets 2015 ATA Thyroid Nodule/DTC Guidelines

Staging for PTC & FTC < 45 yo ≥ 45 yo Stage I Any T, any N, M0 T1 (<2 cm), N0, M0 Stage II Any T, any N, M1 T2 (2-4 cm), N0, M0 Stage III T3, N0, M0 or T1-3, N1a, M0 Stage IVA T4a or any T, N1b, M0 Stage IVB T4b (any N, M0) Stage IVC * The staging system will change in January 2018 (one change is age to 55) 2015 ATA Thyroid Nodule/DTC Guidelines

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)

New Diagnosis: NIFTP International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature. NIFTP= Noninvasive follicular thyroid neoplasm with papillary-like nuclear features Previously classified as FVPTC

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

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

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

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

What changes with cancer? Surgery for cancer

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

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

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

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)

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

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

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)

Who needs RAI? 2015 ATA Thyroid Nodule/DTC Guidelines

(continued)

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

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

Cut-throat surgeons… Why surgery?!

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%)

“High-volume” Thyroid Surgeon The more the surgeon does, the better the outcomes Number/year ranges from 25 to 100

Tricks of the trade Nerve monitoring Latest technology Special ET tube with wires Can avoid dreaded bilateral injury by stopping if first side is injured

More Tricks of the Trade Autotransplantation Transplant normal parathyroids into the muscle Will eventually make their own hormone PTH monitoring in the OR Monitor the levels of parathyroid hormone Helps guide medication after surgery

Big and small 5 g 279.27 g

Summary: 10 Years of Thyroid Cancer Progression Bethesda classification of FNA Genetic/molecular evaluation of indeterminate nodules RAI use more limited resulting in changes in surgical treatment (lobes for low-risk cancer) NIFTP– no longer cancer, but not benign–changing the way we evaluate nodules Less complications with >25 cases/yr

Useful websites American Thyroid Association (ATA) Search “ATA guidelines” American Association of Endocrine Surgery (AAES) EndocrineSurgery.org EndocrineDiseases.org (patient education)

Questions? Cortney Y. Lee, MD, FACS Associate Professor of Surgery Section of Endocrine surgery Cortney.Lee@uky.edu Clinic: (859) 218- 2780