Contemporary Management Guidelines for

“Differentiated Thyroid Cancer”

Yahya Al Badaai, M.D, FRCSC

Otolaryngologist Head & Neck Surgeon
Differentiated Thyroid Cancer
(DTC)
Differentiated Thyroid Cancer
(DTC)

JAMA. 2006;295(18):2164-2167. doi:10.1001/jama.295.18.2164

Differentiated Thyroid Cancer
(DTC)
 Evolution of Management
DTC

Less
Radical
Radical
 DTC Guidlines

• ATA

• NCCN

• LATS

• ESMO

• JTA
 Nodule

Surgery

Initial risk
stratification

ablative/
adjuvant/therapeutic
Rx

Follow-
Up continuous risk
stratification
H&P TSH US

FNAC
 DTC
• History:
• Age (>40 M – 45 F or < 15)
• Gender (M>F)
• Previous thyroid cancer
• Family Hx of thyroid cancer
• Thyroid cancer syndrome (e.g., Cowden’s syndrome, familial polyposis,
Carney complex, multiple endocrine neoplasia [MEN] 2, Werner
syndrome)
• XRT head & neck region during childhood
• Exposure to ionizing radiation from fallout
• History of rapid growth
• Symptoms of invasion (Hoarsness, Dysphagia)
• 18 FDG avidity on PET scanning (33% risk of cancer)
 DTC

• Physical examinations:

• > 4 cm
• Fixation
• Signs of invasion (cord paralysis)
• lymphadenopathy
 DTC

• Laboratory investigation:

• TSH
• Normal or elevated
• Low

• TG

• Calcitonin
 DTC

• Radiological Investigations (US):

• Thyroid & lateral neck US:
• Is there truly a nodule that corresponds to the palpable
abnormality or incidentally on other radiological modalities?
• How large is the nodule?
• Does the nodule have benign or suspicious features?
• Is suspicious cervical lymphadenopathy present?
FNA at > 1 cm

FNA at > 1 cm

FNA at > 1.5 cm

FNA at > 2cm

NO FNA
DTC
DTC
DTC
DTC
DTC
DTC
DTC
 DTC
• High Suspicion US features:

• Hypoechoeic + one or more of the following:

• micro calcifications

• irregular borders

• taller than wider

• pathological lymph nodes

• extra-thyroidal extension

• interrupted macro calcifications

FNA at > 1 cm

FNA at > 1 cm

FNA at > 1.5 cm

FNA at > 2cm

NO FNA
 FNAC

The Bethesda system for reporting thyroid cytopathology: Diagnostic categories and risk of malignancy
 FNAC
Non-
Benign
diagnostic

Repeat
US-FNAC
No Surgery

Non- Us pattern:
diagnostic High risk: repeat 12 m
intermediate risk: 12-24 m
low risk: ? 24 m

Surveillance surgery
 FNAC
AUS/FLUS
Molecular Testing:
• BRAF
• NRAS
• HRAS
• KRAS
Repeat US-FNAC and /
• RET/PTC1
or molecular testing
• RET/PTC3
• PPARY

Inconclusive

• clinical risk factors surgery

Surveillance • sonographic pattern
• patient preference
 FNAC
SUSPECIOUS
FN/SFN
PAPILLARY CANCER

molecular testing molecular testing

surgery surgery
 PAPILLARY CANCER

CENTRAL /
LOBECTOMY / NEAR TOTAL / TOTAL LATERAL NECK
HEMITHYROIDECTOMY DISSECTION

Surveillance

Goals of Surgery:
• Improve overall and disease-specific survival
• Reduce the risk of persistent/recurrent disease and associated morbidity
• Permit accurate disease staging and risk stratification
• Minimizing treatment-related morbidity and unnecessary therapy
 New ATA Guidelines 2015
• >4 cm, or with gross extrathyroidal extension (clinical T4), or
clinical N1 or distant sites M1:

• near total or total thyroidectomy and and gross removal of all

primary tumor

• > 1 cm and < 4 cm with no extra thyroidal extension and cN0:

• can be either a bilateral procedure (near-total or total

thyroidectomy) or a unilateral procedure(lobectomy)

• < 1 cm with no extra thyroidal extension and cN0:

• if surgery is chosen lobectomy should be done

 Previous Recommendations

• All tumor > 1 cm:

• Bilateral surgical procedure (retrospective
studies) :
• Improve survival
• Decrease recurrence rates
• Allow for routine use of RAI remnant ablation
• Facilitate detection of recurrent/persistent
disease during follow-up
 Why The Changes?
• In properly selected patients, clinical outcomes are
very similar following unilateral or bilateral thyroid
surgery
Ito K 2014 Thyroid lobectomy for papillary thyroid cancer: long-term follow-up study of 1,088 cases.
World J Surg 38:68-79
Shah JP 2012 Thyroid lobectomy for treatment of well differentiated intrathyroid malignancy.

Surgery 151:571-579 


• Current more selective approach to RAI ablation

(since the requirement for routine use of RAI ablation was one of the major
reasons given in support of total thyroidectomy in low to intermediate risk
patients)
 Why The Changes?

• Recurrences that develop during long-term follow-

up are readily detected and appropriately treated
with no impact on survival
Vaisman F, Shaha A, Fish S, Michael TR 2011 Initial therapy with either thyroid lobectomy or total
thyroidectomy without radioactive iodine remnant ablation is associated with very low rates of structural
disease recurrence in properly selected patients with differentiated thyroid cancer. Clin Endocrinol (Oxf)
75:112-119
 Why The Changes?
• Surgical complications: (HCUP-NIS)

Volum # Thyroidectomies Complications rate for

total thyroidectomy
Low <10/year 18.9%
(6072 Surgeons)
Intermediate 10-100/year 13.4%
(11544 Surgeons)
High >100/year 7.5%
(4009 Surgeons)

Kandil E, Noureldine SI, Abbas A, Tufano RP 2013 The impact of surgical volume on patient outcomes following thyroid
surgery. Surgery 154:1346-1352
 Why The Changes?

Surgeon Lobectomy Total thyroidectomy

High Volum 7.6% 14.5%

Low volume 11.8% 24.1%

Kandil E, Noureldine SI, Abbas A, Tufano RP 2013 The impact of surgical volume on patient outcomes following thyroid
surgery. Surgery 154:1346-1352
 Japanese experience

• Active Surveillance : (US 1-2/year)

• Micropapillary thyroid carcinoma ( <=1 cm )

• no extra thyroidal extension

• no regional or distant metastasis

• no agressive histology

• not close to the trachea or recurrent laryngeal nerve

Ito Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A 2014 Patient age is significantly related to the
progression of papillary microcarcinoma of the thyroid under observation. Thyroid 24:27-34 

 Japanese experience

Ito Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A 2014 Patient age is significantly related to the
progression of papillary microcarcinoma of the thyroid under observation. Thyroid 24:27-34 

 Japanese experience

Ito Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A 2014 Patient age is significantly related to the
progression of papillary microcarcinoma of the thyroid under observation. Thyroid 24:27-34 

 Japanese experience

Ito Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A 2014 Patient age is significantly related to the
progression of papillary microcarcinoma of the thyroid under observation. Thyroid 24:27-34 

 Management of the Neck

• Level 1< 5%

• Level 2 ~ 53%

• 2a 53%

• 2b 15%

• Level 3 ~70%

• Level 4 ~ 66%

• Level 5 ~ 25%
Iskander et al Thyroid 2013
 Central Neck
Level 6
• cN1: Therapeutic central neck dissection

• cN0: prophylactic ND if: ( weak recommendation)

• T3 or T4 Tumor

• clinically N+ lateral neck

• or to be used for staging

 Lateral Neck

• Level II - V

• cN+ clinically (US & FNAC or TG measurement or

intra-operatively)

• Reduce the risk of recurrence and possibly

mortality
Level VII (Superior mediastinum)
 Revised ATA Initial risk stratifications

• Low Risk for Recurrence:

• INtrathyroidal DTC 1-4 cm

• No local or vascular invasion

• ≤ 5 LN micromets (≤2mm)

• Minimally invasive FTC (Capsular or minor vascular)

• Intermediate Risk for Recurrence:

• All not in low or high risk

• High risk variants of DTC

• Intrathyroidal 1-4 or multifocal micropapilary with local invasion if BRAF V600E

• Nodes 2 mm to 3 cm

• High Risk of Recurrence:

• Gross Extrathyroidal extension

• Incomplete resection

• Distant mets

• large nodes > 3 cm

• extensive vascular invasion in FTC

 I131

• Why I131?

• Ablation of the normal thyroid remnant

• Adjuvant therapy to try to eliminate suspected micrometastases
• Facilitate initial staging by identifying previously undiagnosed
disease, especially in the lateral neck or distant metastasis
• To treat known persistent disease
 I131
• High risk for persistent disease:
• gross extrathyroidal extension
• primary tumor greater than 4 cm
• known/suspected distant metastases
• High risk for recurrence:
• poorly differentiated histology
• vascular invasion
• clinically significant cervical lymph node metastases
• inappropriately elevated postoperative serum Tg
• Decreased recurrence and disease-specific mortality in
high risk patients
 I131

• Not routinely recommend RAI for patients with either

unifocal or multifocal papillary microcarcinomas (<1 cm)
confined to the thyroid
• No change in overall survival
• Increased secondary malignancies (leukemia & salivary
glands )
 I131 Administration
• Quantitative dosimetry

• Blood dosimetry

• Empiric fixed doses (most common):

• 30 – 100 mCi: Intrathyroidal
• 100 – 150 mCi: + LNs
• 200 mCi: distant mets
 Post I131
• WBS

• TG

• 2 – 10 days after ablation therapy

• Important in staging

• May reveal regional or distant metastasis

• Thyroid bed uptake on 1st WBS after ablation dose most likely indicate
residual thyroid tissue
 Page 408 of 411

408
Low Risk
ub.com by 70.209.21.208 on 10/23/15. For personal use only.

Figure 5. Clinical decision-making and management recommendations in ATA low

 409

Low Risk
e.liebertpub.com by 70.209.21.208 on 10/23/15. For personal use only.
Thyroid

Figure 6. Clinical decision-making and management recommendations in ATA low

risk differentiated thyroid cancer patients that have undergone less than total
 Page 410 of 411

410

Intermediate Risk
pub.com by 70.209.21.208 on 10/23/15. For personal use only.

Figure 7. Clinical decision-making and management recommendations in ATA

 Page 411 of 411

411

High Risk
bertpub.com by 70.209.21.208 on 10/23/15. For personal use only.
Thyroid

Figure 8. Clinical decision-making and management recommendations in ATA high

risk differentiated thyroid cancer patients that have undergone total thyroidectomy and
 Take Home Message
• Less aggressive approach is feasible option in
treating a subset of DTC

• US is a valuable tool in stratifying patient at high

risk for malignancy as well as risk stratification and
follow-up

• Post op ablation or adjuvant I131 should be used

more selectively rather than routinely

• Risk stratification is a continuous evolving process

“The good physician treat the disease;
the great physician treat the patient
who has the disease”

–Sir William Osler