Prophylactic Central Compartment Neck Dissection(CCND) for Papillary Thyroid Cancer: Con

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1 Prophylactic Central Compartment Neck Dissection(CCND) for Papillary Thyroid Cancer: Con Christopher R. McHenry, M.D. Vice Chairman Department of Surgery MetroHealth Medical Center Professor of Surgery Case Western Reserve University School of Medicine Cleveland, Ohio

2 LN Metastases at the Time of Initial Surgery for PTC ~35% (20-50%): macroscopic metastases 80-90%: micrometastases Schlumberger MJ. N Engl J Med 1998;338; Noguchi S et al. Surg Clin North Am 1987;67:

3 PTC and LN Metastases Physical exam will miss macroscopic metastases in 40 % Kouvaraki MA, et al. Role of ultrasonogrphy in the surgical management of patients with thyroid cancer. Surgery 143, , 2003

4 US exam prior to thyroidectomy 486 pts with PTC * nonpalpable LN mets identified in 14% Sensitivity - 84% Specificity - 98% PPV - 89% Stulak JM, et al. Arch Surg 141:489-96,2006

5 US for Diagnosis of Central Compartment LN Metastases Sensitivity 30-53%, Specificity 80-86% Identifies only half of LNs found at surgery, due to overlying thyroid gland Hwang & Orloff. Efficacy of Preoperative Neck US in Detection of Cervical Lymph Node Metastases. Laryngoscope 2011: Choi, et al. Preoperative Diagnosis of Cervical Metastatic LNs in PTC: Comparison of US, CT, & combined US with CT. Thyroid, (4): Leboulleux,et al 2007 US Criteria of Malignancy for Cervical LNs in Patients Followed Up for DTC. J Clin Endocrinol Metab. 2007; 92:

6 2015 ATA Guidelines Recommendation 32 Preoperative US (central & lateral neck) for all patients with FNAB or molecular testing that is malignant or suspicious for malignancy prior to thyroidectomy Strong recommendation, moderatequality evidence

7 Therapeutic CCND Guidelines from all major endocrine societies recommend CCND for clinically node positive PTC ( ATA, NCCN, AHNS, European Thyroid Association, etc) Strong Recommendation, Moderatequality evidence

8 Macroscopic LN Metastases Increased recurrence Decreased survival in patients > 45 years Compartment-oriented neck dissection: CCND +/- Lateral Neck Dissection Lundgren, et al. Cancer 106: , 2006 Zaydfudim, et al. Surgery 144: ,2008

9 CCND Removal LNs & fibrofatty tissue between the carotid arteries laterally, from hyoid bone superiorly to innominate artery inferiorly

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12 Prophylactic CCND Defined as a CCND in a patient with PTC & no clinical, radiographic, or intraoperative evidence of abnormal LNs

13 Management Guidelines for Patients with Thyroid Nodules & DTC-2006 American Thyroid Association Guidelines Taskforce Recommendation 27: Routine CND should be considered for all patients with PTC. Recommendation Rating B Thyroid 16(2); , 2006

14 European Consensus There is no evidence that pccnd improves recurrence or mortality rates, but it does allow an accurate staging of the disease that may guide subsequent treatment and follow up Eur J Endocrinol 154; , 2006

15 Revised ATA Management Guidelines for Patients with Thyroid Nodules & DTC Recommendation 36B: Prophylactic CCND considered in patients with PTC with clinically uninvolved central neck LNs (cn0) who have advanced tumors (T3 or T4), clinically involved lateral neck nodes (cn1b), or if information will be used to plan further therapy Weak Recommendation, Low-quality evidence Thyroid 2016; 26:1-133.

16 pccnd for PTC? Biology of the disease Primum non nocerum, first do no harm

17 Prophylactic Central Neck Dissection No randomized controlled trials sufficiently powered to evaluate pccnd for PTC ATA feasibility study estimated a randomized trial would require 5840 patients & cost ~ $15 million Carling T, et al. Thyroid; 2012;22(3):237-44

18 Potential Benefits of CCND for Clinically N0 PTC Treatment of micrometastases with reduced rates of recurrence Lower serum Tg levels Accurate staging to help modify indications for RAI ablation Reduced reoperation in the central neck, which is associated with greater morbidity

19 Central Compartment Recurrence (CCR) for N0 PTC with or without pcnd Author, year pcnd No CND CCR-pCND CCR-NoCND Moreno % 2.4% Hughes % 2% Moo % 5.6% Roh % 4% Sywak % 1.7% Gemsenjager % 2% Total % 2.2%

20 Central Compartment LN Metastases 38-90% of patients with PTC have occult LN metastases in the central neck Median rate of recurrence for clinically N0 PTC is 2% Most micrometastases remain dormant & rarely become clinically significant Noguchi M,et al. International Surgery. 1987;72(2): Randolph G, et al. Thyroid 2012; 22(11): Cranshaw IM & Carnaille B. J Surg Oncol 2008;17:

21 pcnd & Recurrence in PTC: A Metaanalysis 3(1.9%) of 161 in thyroidectomy & pcnd group vs 12 (1.7%) of 713 in thyroidectomy alone Transient hypoparathyroidism(p<0.02): 18-44%-thyroidectomy & pcnd vs 8-14%- thyroidectomy alone Zetoune,et al Ann Surg Oncol 2010;17:

22 Serum Tg following Total Thyroidectomy with or without pcnd Sywak: lower serum Tg and higher rate of athyroglobulinemia with pcnd (? due to more complete thyroidectomy) Hughes, Yoo: found no difference Normalization less critical than change in Tg over time Sywak, et al. Surgery 2006;140(6): Hughes, et al. Surgery 2010; 148(6): Yoo, et al.world J Surgery 2012;36(6):

23 Yoo, et al.world J Surgery 2012;36(6): No difference in RAI uptake in 190 who underwent TT alone (1.2%) vs. 87 TT and CND (0.93%)

24 CND & RAI 3 retrospective studies have suggested that pccnd may affect dosing or obviate I-131 therapy for low risk PTC & no micrometastases Bonnet S, et al J Clin Endocrinol Metab 94: Hartl DM, et al: Ann Surg: 255: ,2012 Hughes DT, et al. Surgery 148: ,2010

25 Influence of pcnd on RAI Treatment Hughes, et al. Surgery 2010;148: Retrospective cohort study: TT (n=65) vs TT & pcnd (n=78) for N0 PTC Central LN metastases 62% Median dose RAI: 30 mci TT group vs 150 mci TT & pccnd group Even with pccnd & higher RAI doses, central compartment recurrence 2% for both groups

26 Hughes and colleagues Concluded that pccnd is of value for determining doses of RAI therapy Alternative conclusion: pccnd lead to the administration of higher doses of RAI without apparent benefit Complications of RAI: salivary ( xerostomia & sialadenitis) & lacrimal dysfunction, dysphagia, dysgeusia & 2 nd malignancies

27 RAI Ablation Sawka and colleagues in systematic literature review could not demonstrate a significant and consistent benefit of I-131 ablation in decreasing cause specific mortality or recurrence Sawka AM, et al Endocrinol Metab Clin North Am 37: , 2008

28 Memorial Sloan Kettering Cancer Center Experience RAI not conclusively proven to reduce recurrence or mortality in absence of distant metastases RAI not given for patients with low risk PTC treated with TT who have T1 or T2 disease with lymph node micrometastses Nixon, IJ. Results of Selective Use of RAI on Survival & Recurrence in Management of PTC Based on MSKCC Risk Group Stratification. Thyroid 23(6): , 2013

29 Postoperative RAI ATA Recommendation 51 RAI after TT for high risk DTC: Strong recommendation, moderate-quality evidence RAI considered after TT for intermediate risk DTC: Weak recommendation, Low-quality evidence Efficacy of RAI for LN micrometastases unclear Thyroid 2016; 26:1-133.

30 Complications of CND in Patients with PTC N=1087 consecutive patients operated on for clinically N0 PTC at a single institution Complication Permanent RLN injury TT (n=394) TT + ICND (n=385) TT + BCND (n=308) P value 4(1%) 2(0.5%) 7(2.3%) Permanent Hypoparathyroidism 25(6.3%) 27(7%) 50(16.2%) < Giordano D, et al. Thyroid 22(9): , 2012

31 Morbidity: Thyroidectomy with (+) or without (-) CND # Patients RLN paralysis Hypoparathyroidism Authors Henry (4%) 0 Gemsenjager (5.6%) 0 1(1.4%) 0 Rosenbaum (1.1%) 1(4.5%) 0 Hughes (3.1%) 2(2.6%) 0 Pereira (4.6%) - Tissell (3.4%) - 6(3.4%) -

32 Thyroid Surgery in the USA Published morbidity for pccnd comes from expert Endocrine surgeons at specialized centers (publication bias) Low volume surgeons ( <3/yr): majority of thyroid surgery & treat majority of patients with thyroid cancer Stavrakis AI, et al. Surgery 2007; 142: Saunders BD, et al. Surgery 2003;134:

33 Secondary Central Neck Dissection Can be performed for metastatic disease following initial TT with no additional morbidity Alvarado R, et al: Surgery 145: , 2009 Shen WT, et al: Arch Surg 145: , 2010 Recurrence in central neck best managed by referral to specialized center with Endocrine surgery expertise

34 Summary Only potential benefit of pccnd : precise LN staging may determine need for RAI ablation? High price of hypoparathyroidism is not offset by any measurable oncologic benefit It is better for experienced surgeons to perform therapeutic operations for rare recurrences in central neck than for inexperienced surgeons to perform pccnd in all patients

35 Conclusions Balance between risks and benefits favors total thyroidectomy alone for clinically N0 PTC No proven benefit for pccnd

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