Joint Hospital Surgical Grand Round United Christian Hospital Review of Central Compartment Dissection in Papillary Carcinoma of Thyroid Joint Hospital Surgical Grand Round 2nd February 2013 Dr. WY Kwan United Christian Hospital

Outline Introduction Lymph node metastasis in papillary carcinoma of thyroid (PTC) Pattern and significance Central compartment dissection (CCD) Principles and definition Benefits and complications of prophylactic CCD Current guidelines on prophylactic CCD Extent of dissection Conclusion

Thyroid Cancer The most common endocrine malignancy ~ 650 new cases in 2010 in HK Papillary thyroid carcinoma (PTC): the most common histological subtype ~ 80% Hong Kong Cancer Registry. http://www3.ha.org.hk/cancereg/Statistics.html#cancerfacts

Lymph Node Metastasis in PTC Cervical lymph nodes are the principle sites of metastasis 20% - 80% of patients with PTC Central compartment > Lateral compartment White ML et al. Central lymph node dissection in differentiated thyroid cancer. World J Surg 2007;5:895-904

Central compartment = Level VI Lateral compartment = Levels II - V IIB IIA VA VB III IB IA IV VI VII Central compartment = Level VI Lateral compartment = Levels II - V American Thyroid Association Surgery Working Group et al. Consensus statement on the terminology and classification of central neck dissection for thyroid cancer. Thyroid 2009;11:1153-8.

Patterns of LN Metastasis Thyroid Gland Ipsilateral central compartment Contralateral central compartment Thyroid tumour cells spread through the lymphatic system in a sequential fashion Central compartment is most commonly involved Skip metastasis (5% to 20%) Contralateral lateral compartment Ipsilateral lateral compartment Mediastinal compartment

Significance of LN Metastasis In The Central Compartment?

LN Status NOT Included In Most Prognostic Scoring Systems for PTC AMES- Age, Metastasis, Extrathyroidal extension, Size AGES- Age, Grade, Extrathyroidal extension, Size MACIS- Metastasis, Age, Completeness of resection, Invasion (extrathyroidal), Size (modification of the AGES system) TNM staging- Tumor, Node, Metastasis AMES from Lahey clinic – age < 40 in man or < 50 in women, size < 5cm = low risks, high risks if any risk factor AGES from Mayo clinic – age < 45, size < 4cm FactorsScoredistant Metastasis: Did the tumor spread to other parts of the body outside of the region of the neck?yes = 3 no = 0Age at the time the tumor was foundLess than 39 years = 3.1 over 40 = 0.08 x ageInvasion: Did the surgeon see that the tumor had extended beyond the thyroid into other regions of the neck?yes = 1 no = 0Completeness of resection: Were there parts of the tumor that the surgeon was unable to remove (for example a part that was attached to the windpipe)?yes = 1 no = 0Size of tumor (measured by the pathologist)0.3 x size in cm 20-year survival rate according to MAICS scoreMAICS Score< 6.06.0 - 6.997.0 - 7.99> 8.020 yr Survival99%89%56%24%

Significance of LN Metastasis LN metastasis in PTC probably associated with a higher rate of loco-regional recurrence ↑no. of LN metastasis in central compartment  ↑ risks of lateral compartment metastasis as well ↑↓ Hay ID et al. Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery. 1992;112;6:1139-46. discussion 1146-1147 Spires JR et al. Metastatic papillary carcinoma of the thyroid: the significance of extranodal extension. Head Neck 1989;11: 242-246

Significance of LN Metastasis Conflicting data on the impact of LN metastasis on survival No prospective RCT available Swedish study - 5123 patients Lymph node metastasis was associated with diminished survival, even when adjusted for TNM staging Harwood J et al. Significance of lymph node metastasis in differentiated thyroid cancer. Am J Surg. 1978;136:107-112 Lundgren CI et al. Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study. Cancer. 2006;106;3:524-531 Hay ID et al. Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery. 1992;112;6:1139-46. discussion 1146-1147 Spires JR et al. Metastatic papillary carcinoma of the thyroid: the significance of extranodal extension. Head Neck 1989;11: 242-246

LN Dissection - Principles Compartment-oriented LN clearance Berry picking not recommended

Central Compartment Dissection (CCD) Pre-cricoid laryngeal (Delphian) nodes Paratracheal nodes Pre-tracheal nodes Central Compartment Dissection (CCD) Bilateral CCD  Bilateral paratracheal LN Ipsilateral CCD  Ipsilateral paratracheal LN

LN Dissection - Definitions Therapeutic- Clearance of lymphatic tissues when there are involved LNs preoperatively or intraoperatively Prophylactic- No suspicious LN preoperatively or intraoperatively clinical palpation, USG, FNAC, intraoperative inspection frozen section

Routine Prophylactic Central Compartment Dissection For Patients with PTC?

Use Of USG In Detecting LN Metastasis Sensitivity in detecting cervical LN metastasis: 40 – 83% Argument: “In papillary thyroid cancer, preoperative central neck ultrasound detects only macroscopic surgical disease, but negative findings predict excellent long term regional control and survival” “USG of the central compartment is an age-independent predictor for survival and central compartment recurrence-free survival. Stulak JM et al. Value of preoperative ultrasonography in the surgical management of initial and reoperative papillary thyroid cancer. Arch Surg 2006;141;5:489-494. discussion: 494-496

Prophylactic CCD And Serum Thyroglobulin (Tg) Popadich et al, retrospective multicenter study (Australia, USA, UK) 606 patients with PTC, clinically node –ve Group A: Total thyroidectomy Group B: Total thyroidectomy with routine CCD 78% ipsilaterasl CCD Popadich A et al. A multicenter cohort study of total thyroidectomy and routine central lymph node dissection for cN0 papillary thyroid cancer. Surgery. 2011;150;6:1048-57

Prophylactic CCD And Serum Thyroglobulin (Tg) Stimulated Thyroglobulin values ng/mL p = 0.025 NS Popadich A et al. A multicenter cohort study of total thyroidectomy and routine central lymph node dissection for cN0 papillary thyroid cancer. Surgery. 2011;150;6:1048-57 NS = Not statistically significant

Prophylactic CCD And Recurrence Meta-analysis, 5 retrospective studies 1264 patients, FU 6 months to 27 years Group A: Total thyroidectomy + prophylactic CCD Group B: Total thyroidectomy alone Local recurrence rates: Group A: 2.02% Odds ratio= 1.05 (CI 0.48-2.31) Group B: 3.92% Not Significant “ the available studies have substantial limitations…” Zetoune T et al Prophylactic central neck dissection and local recurrence in papillary thyroid cancer; a meta-analysis Ann Surg Oncol. 2010; 17:3287-93

Prophylactic CCD and Survival Comparative study from Sweden 562 patients, 13-year FU Disease-specific mortality rate in CCD (1.6%) VS no CCD (1.9%) Tisell LE et al. Improved survival of patients with papillary thyroid cancer after surgical microdissection. World J Surg 1996. 20:854–859.

Complication Rates Of Total Thyroidectomy +/- CCD Transient RLN injury: 1% to 13% Permanent RLN injury: 0% to 3.6% Transient hypoparathyroidism: 14% to 60% Permanent hypoparathyroidism: 0% to 11% Lee YS et al. Extent of routine central lymph node dissection with small papillary thyroid carcinoma. World J Surg 2007;10:1954-9. Henry JF et al. Morbidity of prophylactic lymph node dissection in the central neck area in patients with papillary thyroid carcinoma. Langenbecks Arch Surg 1998;2:167-9. Pereira JA et al. Nodal yield, morbidity, and recurrence after central neck dissection for papillary thyroid carcinoma. Surgery 2005;6:1095-100 Sywak M et al. Routine level six lymphadenectomy reduces postoperative thyroglobulin levels in papillary thyroid cancer. Surgery 2006;140:1000–1005 Roh JL et al. Total thyroidectomy plus neck dissection in differentiated papillary thyroid carcinoma patients: Pattern of nodal metastasis, morbidity, recurrence, postoperative levels of serum parathyroid hormone. Ann Surg 2007; 245:604–610. Palestini N et al. Is central neck dissection a safe procedure in the treatment of papillary thyroid cancer? Our experience. Langenbecks Arch Surg 2008;393:693–698.

Complications Of CCD Meta-analysis from UK, 5 studies, 1132 patients For every 7.7 CCD performed with thyroidectomy, there was one extra case of temporary hypocalcaemia when compared to thyroidectomy alone “…..There is no increased permanent morbidity by performing the procedure at the same time as thyroidectomy.” 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

Prophylactic CCD: Continuous Debates Pros LN metastasis have a negative effect on patient outcome LN metastasis in the central neck cannot be reliably identified preoperatively or at operation Accurate staging and guides RAI treatment No increased risks of permanent complications Reduce morbidity of reoperation for central neck recurrence Cons Increased risks of temporary hypoparathyroidism Survival benefit not certain

A Lack Of High Level Evidence Given the low rates of recurrence 5840 patients would have to be recruited in an RCT to achieve adequate statistical power Carling T et al. American Thyroid Association design and feasibility of a prospective randomized controlled trial of prophylactic central lymph node dissection for papillary thyroid carcinoma. Thyroid 2012;3:237-44.

Current Guidelines On Prophylactic Central Compartment Dissection?

Comparison Of Guidelines On Prophylactic CCD National Comprehensive Cancer Network (1/2013) “Can be considered”: age <15 or > 45 years; radiation Hx; M1; extrathyroidal extension; tumour > 4cm; aggressive histological variant American Thyroid Association 2009 “Ipsilateral/ bilateral CCD may be performed”, esp. T3 / T4 tumours. TT without CCD may be appropriate for T1/T2 and noninvasive PTC British Thyroid Association 2007 Should be performed if: male / age>45 / tumour>4cm /extracapsular or extrathyroidal extension/ suspicious nodes intraoperatively European Thyroid Association 2006 Controversial benefits; No evidence to improve recurrence or mortality; may perform to guide treatment and follow-up

Comparison Of Guidelines On Prophylactic CCD American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi 2006 “should be performed if the surgeon has specific training” for and experience with thyroid surgical techniques Papillary thyroid microcarcinoma (<1cm in max diameter) without LN involvement may avoid CCD Latin American Thyroid Society 2009 “should be performed” for T3 / T4 tumours Japanese Society of Thyroid Surgeons 2011 Routine central compartment dissection is recommended (Policy of RAI only in high risks patients)

Should We Perform Ipsilateral Or Bilateral Central Compartment Dissection?

Extent of CCD: Unilateral VS Bilateral 1 out of 4 patients with bilateral CCD done had +ve LN metastasis in contralateral central compartment Risks of transient hypoparathyroidism Unilateral CCD < Bilateral CCD Sadowski BM, et al. Routine bilateral central lymph node clearance for papillary thyroid cancer. Surgery. 2009 146(4):696-703; discussion 703-5 Grodski S, Cornford L, Sywak M et al. Routine level VI lymph node dissection for papillary thyroid cancer: surgical technique. ANZ J Surg 2007;4:203-8

What If The Policy Of Prophylactic CCD Is Not Implemented?

Alternative Options Watchful waiting Empirical radioactive iodine therapy Regular clinical exam during follow-up Surveillance USG of neck Monitoring of thyroglobulin level

Conclusions Therapeutic LN dissection if LN metastasis confirmed Prophylactic CCD helps in accurate staging of PTC but carries increased risks of transient hypoparathyroidism Prophylactic CCD in high risks groups by experienced surgeons Ipsilateral CCD could reduce morbidity of transient hypocalcaemia compared with bilateral CCD

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