JHSGR

Management of Papillary Ca Thyroid

Chris Cheng Tsz Ling

Princess Margaret Hospital

Introduction Thyroid carcinoma has the fastest rising incidence

of all major cancers, ↑4% per year Papillary thyroid carcinoma(PTC) is the most

common type of differentiated thyroid carcinoma, incidence x 2 throughout 25 years

Excellent prognosis, 10-year cancer specific survival rate >90%

Locoregional recurrence (LRR) is a major cause of disease morbidity

Grubbs EG, Rich TA, Li G, et al. Recent advances in thyroid cancer. Curr Probl Surg 2008;45:156 –250

Cancer incidence and mortality in Hong Kong 1983–2008: Hong Kong Cancer Registry, Hong Kong

Agenda

The optimal extent of surgery

Prophylactic central neck LN dissection

Rationale for use of adjuvant radioactive iodine (RAI) remnant ablation

Thyroidectomy

Total/Near total Thyroidectomy Vs Lobectomy

Total thyroidectomy (n=43227) Vs Lobectomy (n=8946)

≥ 1cm CA thyroid, Lobectomy was associated with

15% higher risk of recurrence (p=0.04)

31% higher risk of death (p=0.009)

< 1cm CA thyroid, no difference in recurrence or survival

Bilimoria et al. Extent of surgery affects survival for papillary thyroid cancer. Ann Surg 2007 Sep;246(3):375-81

American Thyroid Association recommendation:

Lobectomy: for <1cm, low risk, unifocal, intrathyroidal papillary carcinoma without cervical LN or history of head & neck irradiation

Near-total / Total thyroidectomy: for >1cm

Neck LN Dissection

Neck Dissection Therapeutic

- Clinically evident and biopsy proven LN involvement

Prophylactic

- No clinical evidence of LN

- HOT debate: Prophylactic Central LN dissection(level VI)

ATA Guideline. Consensus Statement on the Terminology and Classificationof Central Neck Dissection for Thyroid Cancer. Thyroid. Volume 19, Number 11, 2009

Central neck dissection may be extended to:-Retropharyngeal-Retroesophageal-Paralaryngopharyngeal (superior vascular pedicle) -Superior mediastinal (inferior to innominate artery)

Central neck dissection (minimum)-Pre-laryngeal-Pre-tracheal-Para-tracheal

Central Neck dissection SEER (Surveillance, Epidemiology, and End Results) database

9904 Papillary thyroid cancer

Cervical LN met in papillary cancer of Age>45

Independent risk factor for decreased survival

The most common site for lymph node metastases and DTC recurrence is within the central compartment

Roh JL et al. Total thyroidectomy plus neck dissection in differentiated papillary thyroid carcinoma patients: pattern of nodal metastasis, morbidity, recurrence, and postoperative levels of serum parathyroid hormone. Ann Surg 2007 245:604–610.

Central neck dissection may convert some patients from cN0 to pathologic N1a

Central Neck dissection

Mayo clinic 60-year observation in 900 patients with <1cm microcarcinoma In 450 patients with any form of LN surgery done,

30% lymph node involvement at initial surgery

80% recurrence at central LN

Hay ID et al. Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period. Surgery 2009. 144:980–987.

CND may reduce recurrence

In 950 Papillary thyroid cancer patients Stage I 45%, Stage II 25%, Stage III 22%, Stage IV 6%

75% LN dissection done (mostly CND only)

Recurrences LN dissection: 6.8%

No LN dissection: 16.5% (p<0.001)

Stage I (1%), Stage II (6%), Stage III (6%), Stage IV (77%)

No difference in 10-yr / 15-yr survival Toniato A et al. Papillary thyroid carcinoma: factors influencing

recurrence and survival. Ann Surg Oncol 2008;15: 1518–1522.

Central Neck Dissection

Seems Improve survival in comparing observational studies

Tisell LE et al. Improved survival of patients with papillary thyroid cancer after surgical microdissection. World J Surg 1996. 20:854–859.

Central Neck Dissection

Increases the proportion of patients who appear disease free with unmeasureable Tg levels 6 months after surgery

undetectable TG levels

Total thyroidectomy + CND: 72%

Total thyroidectomy only: 43% (p<0.001)

Sywak M et al. Routine ipsilateral level VI lymphadenectomy reduces postoperative thyroglobulin levels in papillary thyroid cancer. Surgery 2006. 140:1000–1007

Central neck dissection increases complications?

Complications of thyroidectomy alone Vs thyroidectomy + CND

Chrisholm et al. Systematic review and meta-analysis of the adverse effects of thyroidectomy combined with central neck dissection as compared with thyroidectomy alone. Laryngoscope 2009 Jun;119(6):1135-9

Complications of thryoidectomy alone Vs thryoidectomy + CND

Chrisholm et al. Systematic review and meta-analysis of the adverse effects of thyroidectomy combined with central neck dissection as compared with thyroidectomy alone. Laryngoscope 2009 Jun;119(6):1135-9

Central Neck Dissection

All existing literatures are cohort studies

No RCT

American thyroid association has commented it is NOT feasible to do an RCT on prophylactic central neck dissection

Need to randomize 5840 patients to have enough power to show a difference in recurrence or complications!

American Thyroid Association Design and Feasibility of a Prospective Randomized Controlled Trial of Prophylactic

Central Lymph Node Dissection for Papillary Thyroid Carcinoma. THYROID. Volume 22, Number 3, 2012

American Thyroid Association (ATA) guideline – Central neck dissection

Prophylactic central-compartment neck dissection (ipsilateral or bilateral)

PTC with clinically uninvolved central neck LN,

especially for advanced primary tumors (T3 or T4).

Recommendation rating: C

Near-total or total thyroidectomy without prophylactic central neck dissection

for small (T1 or T2), noninvasive, clinically node-negative PTCs.

Recommendation rating: C

These recommendations should be interpreted in light of available surgical expertise.

Radioactive Iodine Ablation

Role of post thyroidectomy RAI1.Remnant ablation (to facilitate detection

of recurrent disease and initial staging)

2.Adjuvant therapy (to decrease risk of recurrence and disease specific mortality by destroying suspected, but unproven metastatic disease), or

3.RAI therapy (to treat known persistent disease).

↓ Recurrence and cancer death in Stage 2/3 disease

Mazzaferri EL, Jhiang SM 1994 Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97:418–428.

RAI improved survival

The single most powerful prognostic indicator

- ↑ increase disease-free interval (p<0.001)

- ↑ increase survival

Samaan Na et al. The results of various modalities of treatment of well differentiated thyroid carcinomas: a retrospective review of 1599 patients. J Clin Endocrinol Metab 1992. 75:714–720.

The National Thyroid Cancer Treatment Cooperative Study Group (NTCTCSG)

2936 patients

median follow-up of 3 years

Near-total thyroidectomy followed by RAI therapy and aggressive thyroid hormone suppression therapy

Improved overall survival of patients with NTCTCSG stage II-IV disease

No impact of therapy in stage I disease

Jonklaas J et al. Outcomes of patients with differentiated thyroid carcinomafollowing initial therapy. Thyroid 2006. 16:1229–1242.

Mayo Clinic experience on MACIS low risk papillary thyroid cancer

Hay ID, McConahey WM, Goellner JR. Managing patients with papillary thyroid carcinoma: insights gained from the Mayo Clinic’s experience of treating 2,512 consecutive patients during 1940 through 2000. Trans Am Clin Climatol Assoc 2002.113:241–260

RAI in papillary thyroid microcarcinoma

Hay ID et al. Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period. Surgery 2009. 144:980–987.

RAI after thyroidectomy for <1cm PTM did not reduce recurrence

RAI in papillary cancer

RAI did not show benefit in low risk disease

Recurrence and survival benefits restricted to: >1.5cm

Residual disease following surgery

ATA guideline on RAI remnant ablation

Recommended for T3-4 or M1

Recommended for selected cases in 1-4cm thyroid cancers with:

Lymph node metastases, or

high risk features

Age >45, tumor invasion, individual histology, incomplete resection

Recommendation rating: C

NOT recommended for patients with:

unifocal cancer <1 cm without other higher risk features

Recommendation rating: E

multifocal cancer when all foci are <1 cm in the absence other higher risk features

Recommendation rating: E

ATA guideline on RAI remnant ablation

Conclusion

Individualized management according to risk stratification

Low Vs High risk

Total/Near-total Thyroidectomy is standard for >1cm papillary thyroid cancer

Prophylactic Central neck dissection is indicated for T3-4 tumors to reduce local recurrence

For T1-2 tumors, need to balance benefits and complications

RAI mainly indicated for T3-4 & M1 disease

Thank you