Controversies in the Surgical Management of Thyroid Cancer

AACE Southern States February 10-12, 2017

Carmen C. Solórzano Professor of Surgery

Chief, Division of Surgical Oncology and Endocrine Surgery Vanderbilt University Medical Center

Nashville, TN

Current Controversies

• Lobectomy is it enough? • Prophylactic central neck dissection: yes or

no? • Management of microcarcinoma: surveillance

or surgery?- will not be covered today

Case • 75 yo male incidental left thyroid mass on carotid

exam. Physical exam: left lobe 2cm firm mass • Prior carotid endarterectomy right neck • US 1.7 cm lobulated solid hypoechoid nodule with

micro-calcification. No adenopathy. FNA= insufficient

22200935

Thyroid Lobectomy With or without isthmus Total lobectomy or

Near total lobectomy

Always save the parathyroids, auto-transplant them if necessary

When is Lobectomy indicated?

• To provide a diagnosis for indeterminate nodules • To remove “low risk” thyroid cancer • When the risk of a total thyroidectomy is “too

high” • To treat compression symptoms from benign

goiters (including sub-sternal goiters) • For cosmetic reasons • To remove a single toxic thyroid nodule

When Not? • In patients who have a family history of cancer or

radiation exposure • When the patient has bi-lobar thyroid nodules

and low risk thyroid cancer (this is relative) • High risk thyroid cancer • When there is obvious clinically positive lymph

nodes • Graves’, Hashimoto’s goiters, Plummer’s • Bilateral thyroid nodules with compression

Thyroid Nodules are Common • Palpable in 5% women and 1% men • By ultrasound present in 19-68% • Our objective is to exclude cancer and treat

symptoms • Chance of cancer in a thyroid nodule ranges

from 5-15%

Thyroid Cancer Incidence

• Increasing (x3 since 1970) • In the USA - 39% of all thyroid cancer is a

microcarcinoma (less than 1cm) • We are faced with a “Tsunami” of

microcarcinomas and low risk thyroid cancer • Lobectomy is a great option for micro-

carcinoma and “low risk” thyroid cancer

• New diagnostic techniques • Increased medical surveillance • Increased access to medical services

Vaccarella S,et al. New England J of Med 2016; 375:7:614-7

Massive increases in detection of small papillary lesions caused by a large reservoir of asymptomatic, nonlethal disease known

to exist in the thyroid gland.

Vaccarella S,et al. N Engl J Med 2016; 375:614-7

expected

observed incidence

observed incidence

expected

Overdiagnosis (1993 – 2007)

Overdiagnosis women

(2003 – 2007)

Overdiagnosis men

(2003 – 2007)

USA 228,000 70 – 80% 45%

Italy 65,000 70 – 80% 70%

France 46,000 70 – 80% 70%

Japan 36,000 50% <25%

South Korea

77,000 90% 70%

Vaccarella S,et al. N Engl J Med 2016; 375:614-7

12 countries / two decades 470,000 women + 90,000 men

When to Recommend FNA of a Thyroid Nodule

• Not every nodule needs biopsy • The risk of cancer in the nodule can be stratified

based on the ultrasound characteristics of the nodule • No biopsy for thyroid nodules <1cm

High Risk Features (70-90% cancer): Biopsy at 1 cm or greater

Solid and hypoechoic with one of these: microcalcifications, irregular border, taller>wide, rim calcium with extrusion, extrathyroidal extension

Look at the Lateral Lymph Nodes they can Tell a Story

Level 4 Lateral Compartment

Intermediate Risk Features (10-20% cancer)

Biopsy at 1 cm or greater

Solid, hypoechoic, smooth border

Low Suspicion (5-10%) Biopsy >1.5cm

Very Low (<3%) Biopsy >2cm

Benign (<1%) No Biopsy

cystic

Diagnostic Categories and Cancer Risk Bethesda Cytology Category Malignancy

risk % by cytology

Malignancy rates in surgical series % (range)

Non-diagnostic (I) 1-4 20 (9-32)

Benign (II) 0-3 2.5 (1-10)

AUS/FLUS (III) 5-15 16 (6-48) FN/SFN (IV) Follicular/Hurthle neoplasm

15-33 25 (14-33)

Suspicious for Malignancy (Susp- usually PTC) (V)

60-75 70 (53-97)

Malignant (VI) 97-99 99 (94-100)

Bethesda Cytology Categories: Suspicious for PTC or PTC

• The risk of cancer in my hospital is: 68% for Bethesda V >95% for Bethesda VI • When is thyroid lobectomy enough? does extent of thyroidectomy improve survival? does it improve recurrence?

Bilimoria, KY et al. Ann Surg 2007; 246:3:375-81. Using the National Cancer Database (NCDB) ATA guidelines en 2009 reflected the results of this paper

N= >52,000 patients with PTC

Total thyroidectomy improves survival for cancer >1cm

Surveillance Epidemiology and End Results=SEER 1988-2001

• 22,724 patients with PTC: 5,964 had a lobectomy • Controlling for tumor size no difference in survival

with more aggressive surgical procedure (i.e. Total) • Average follow-up: 9.1 years

Disease Specific Survival

2010 Arch Oto Head and Neck

• Tumor size is not the only factor to consider • After adjusting for other clinical and tumor factors no

survival advantage was seen in patients with 1-4cm cancers

• Medial follow-up: 82 mos

Ann of Surg Oct 2014 1998 to 2006 Using the National Cancer Database

• How good are the registries that send data to the national cancer database or SEER?

• We analyzed cases of thyroid lobectomy for WDTC to see if the surgery of primary site was correctly coded

• 40% of thyroid lobectomies were incorrectly coded • 27% of the patients coded as having lobectomy

actually had a total thyroidectomy

Annals of Surgical Oncology 2016- using the TN Cancer Registry

Surgery 2012 Memorial Sloan Kettering

• 1,088 patients with PTC underwent lobectomy and no RAI

• Follow-up 17 years: Cause specific survival at 25 yrs was >95.2%

• Recurrence rate in the remnant thyroid at 25 yrs was 6.5%

• Lobectomy is a valid alternative for patients <45 yrs of age, tumor diameter <4cm, no ETE and no clinically involved lymph nodes

WJS 2014

Cause Specific Survival

• 20 year TR for patients with microscopic intra-thyroid tumors was 5.2% and those with MEE was 2.4%

• Clinical T1/T2 N0M0 with min ETE may not lead to greater recurrence at any anatomic site

• Leading to doubt about the current guideline recommendations of the ATA

2015 ATA Initial Risk Stratification: Risk of Structural Disease Recurrence

“Punishment should fit the crime”

Selection Very Important: Lobectomy Total Thyroidectomy?

• Ultrasound characteristics suggesting extra-thyroidal extension

• Intraoperative evidence of extra-thyroidal extension and or lymph node involvement

• Bilobar thyroid nodules • Patient preference

Ultrasound Characteristics Suggesting Higher Risk Cancer

Posterior location violating the capsule?

Path of RLN Extrathyroidal extension?

More Selective Approach to the Extent of Thyroidectomy

• Previous guidelines endorsed total thyroidectomy for >1cm cancer

• Extent of initial thyroidectomy has little impact on disease specific survival and recurrence is low (with proper selection)

• More selective approach to RAI ablation- less of a mandate for total thyroidectomy

• Higher complications with Total vs. Lobe • No need for life long levothyroxine

ATA guidelines

Extent of Thyroidectomy For Differentiated Thyroid Cancer (R35)

• For thyroid cancer >4cm, gross ETE, clinically apparent metastatic disease (cN1 or M1)

total or near total thyroidectomy • >1 to <4cm, no ETE, cN0 total or lobectomy; Lobectomy

may be sufficient for low risk PTC or Follicular carcinoma…team approach

• If surgery chosen for <1cm cancers (no ETE, cN0) lobectomy

ATA guidelines

• Low risk ultrasound characteristics • The patient is not very anxious • Afima GEC- benign, Thyroseq v2 negative,

ThyGenX/ThyraMIR negative

Factors to Consider in Decision for Surgery vs. Surveillance For Indeterminate Nodules

Alexander NEJM 2012, Nikiforov Thyroid 2015 Cancer 2014, Labourier JCEM 2015

What about the Surgical Management

of the Cervical Lymph Nodes

Carty et al. Thyroid 2009

Central Neck: Between carotids from hyoid to innominate artery

The Neck Compartments and Levels: Be Familiar with Terminology so we

can Speak the Same Language

Other Definitions

• Prophylactic dissection: When pathologic LNs are NOT detected clinically or by image (cN0)

• Therapeutic dissection: When LNs are grossly involved by ultrasound or exam

• Unilateral/Ipsilateral dissection: Para-tracheal LNs same side as the cancer, + pre-tracheal, + pre-laryngeal

ANATOMY 1-Removal of the pre-laryngeal nodes and pre-tracheal nodes up to the innominate artery 2-Para-tracheal: the recurrent nerves carefully dissected with removal of nodes anterior and posterior 3-Remove nodes behind the right carotid and inferior thyroid arteries 4-Preserve blood supply to the parathyroids and transplant as needed

Agreement: Therapeutic Central Neck Dissection

• A therapeutic central neck dissection should be performed in the presence of clinically involved lymph nodes

Why Therapeutic Central Neck or Lateral Dissections

• Clinically involved LN can not be adequately treated with RAI

• Metastatic lymph nodes are the most common cause of recurrent/persistent disease after initial treatment

• Presence of gross lymph node metastasis may decrease long term survival and increase recurrence rates

Podnos Am Surg 2005, Adam JCO 2015, Zaydfudim Surgery 2008, Leboulleux JCEM 2005

Disagreement on Prophylactic Central Neck Dissection

• The central neck is difficult to asses by US • Some contend that this procedure decreases

recurrence • Others say recurrence rates are the same and

the morbidity is too high • Others argue you can avoid RAI if you properly

stage patients

One Randomized Trial by Viola et al.

• 181 patients with PTC • Total tx with bilateral pCND vs total thyroidectomy • No evidence of lymph node involvement by

ultrasound or at the time or the surgical procedure • Primary end point: successful ablation and incidence

or persistent or recurrent disease at 5years • Secondary end point: complications

Randomized Trial Viola et al. Cont…

• Mean tumor size 1.6cm for both groups • 46% of those with pCND had occult LN+ • Median follow-up was 60 months • Biochemical or structural persistent dz in 8% vs.

7.5% (p=0.09) for TT vs. TT+pCND • The TT group required significantly more RAI

treatment to achieve successful ablation • Higher prevalence of permanent

hypoparathyroidism in the TT+pCND 19.4% vs. 8% p=0.02

Prophylactic Central Neck Dissection Meta-analysis

Total Tx PCND

Total Tx only

Local Rec Total Tx PCND

Local Rec Total Tx

Local Rec rate significantly different?

Zetoune 2010

161 713 2.02% 3.92% No

Wang 2013

745 995 4.7% 7.9% No Treat 30 to avoid 1

Lang 2013

1,592 1,739 4.7% 8.6% Yes

Total 3,997 5,506 Mean 4.5%

Mean 7.05%

Complications are similar with or without pCND but most reports are from Specialized centers with high volume patients and surgeons

Prophylactic Central Neck Dissection My Review of the Literature

• When performed-50% will have

micrometastases • Loco-regional recurrence is similar with or

without pCND (short term) • Improved staging and upstaging • In the literature—RAI is universally given

when positive lymph nodes are encountered even when LN mets are microscopic

Case • 75 yo male incidental thyroid mass on carotid exam • US 1.7 cm lobulated solid hypo-echoid nodule with

calcification. No adenopathy. FNA= insufficient • Because I was unsure about ETE I performed:

Total thyroidectomy Path: PTC with ETE+ min 1/10 LN <2mm lymph node met Stage III due to N1a and min ETE/T3 But low/intermediate ATA risk?

RAI Yes/No: Low/Intermediate Risk ATA Recurrence Risk

Description Evidence: RAI improves DSS

Evidence: RAI improves DFS

RAI Indicated?

ATA low risk T1a, N0,M0

Size <=1cm (uni or multifocal)

No No No

ATA low risk T1b, T2,N0,M0

Size >1-4cm No Conflicting Not Routine

ATA low/interm T3,N0,M0

Size >4cm Conflicting Conflicting Consider

ATA low/interm T3,N0,M0

Microscopic ETE, any size

No Conflicting Consider

ATA low/interm T1-3,N1a,M0

Central compartment LN mets

No, except possibly >=45yo

Conflicting Consider

ATA low/interm T1-3,N1b,M0

Lateral compartment LN mets

No, except possibly >=45yo

Conflicting Consider

Includes Nx/MX

My Opinion • It is reasonable to perform ipsilateral

prophylactic CND if the information will change practice and you have access to experienced surgeons

• Better staging- could avoid RAI in micromets • For example: in the case presented will the

finding of 1/10 LN micro met lead to avoidance of RAI?

• ? Less local recurrence- unclear

Prophylactic Central Neck Dissection

• Prophylactic central compartment dissection should be considered in patients with PTC with cN0 who have advanced primary tumors (T3 or T4) or clinically involved lateral lymph nodes, or if the information will be used to plan further therapy.

(Weak Recommendation- Low quality evidence)** • Thyroidectomy without prophylactic CND is appropriate for

small (T1 or T2), noninvasive, cN0 PTC and most Follicular cancers.

(Strong Recommendation- Moderate quality evidence) **Interpret in light of local expertise

ATA guidelines 2015

Conclusions

•Thyroid lobectomy is an excellent choice for low risk thyroid cancer and indeterminate neoplasms • Complications of lobectomy are lower • Prophylactic central neck dissection is controversial- reasonable if changes managment and you have access to high volume surgeons

Thank you

RAI Yes/No: High Risk

ATA Recurrence Risk

Description Evidence: RAI improves DSS

Evidence: RAI improves DFS

RAI Indicated?

ATA high risk T4 Any N Any M

Any size, gross ETE

Yes Yes Yes

ATA high risk M1 Any T Any N

Distant metastases

Yes Yes Yes