Annals of Surgical Oncology

, Volume 24, Issue 7, pp 1935–1942 | Cite as

The Impact of Pathologically Positive Lymph Nodes in the Clinically Negative Neck: An Analysis of 39,301 Patients with Papillary Thyroid Cancer

  • Ewa Ruel
  • Samantha Thomas
  • Jennifer M. Perkins
  • Sanziana A. Roman
  • Julie A. Sosa
Endocrine Tumors



Management of patients with low-risk papillary thyroid cancer (PTC) with clinically uninvolved lymph nodes (cN0 LNs), but who harbor metastatic central LNs (pN1a), remains unclear. The number of central LNs examined, radioactive iodine (RAI) utilization, and survival were compared across cN0 patients based on pN stage: pN0 (negative) versus pNx (unknown) versus pN1a (pathologically positive).


Adults with a PTC ≥1 cm who were cN0 preoperatively were compared based on surgical pathology using the National Cancer Data Base (NCDB; 2003–2011), after univariate and multivariate adjustment. Overall survival (OS) was examined using Kaplan–Meier curves, the log-rank test, and Cox proportional hazards modeling.


Overall, 39,301 patients were included; median tumor size was 1.9 cm. More LNs were examined for pN1a versus pN0 diagnosis (pN1a median = 5 LNs vs. pN0 median = 2 LNs; p < 0.0001), with a median of two central LNs found to be positive on surgical resection. Compared with pN0, pN1a patients were 78% more likely to receive RAI (odds ratio 1.78, 95% confidence interval [CI] 1.65–1.91; p < 0.0001). After adjusting for receipt of RAI, no difference in OS was observed for pN1a versus pN0 or pNx patients (p = 0.72). Treatment with RAI was associated with improved OS (hazard ratio 0.78, 95% CI 0.62–0.98, p = 0.03), but the effect of RAI did not differ based on pN stage (interaction p = 0.67).


More LNs were examined for positive versus negative pN diagnosis in patients with cN0 PTC. Unsuspected central neck nodal metastases in cN0 PTC patients are associated with increased RAI utilization, but no survival difference.



This work was supported by NIHT-32 Training Grant 2T32DK007012 - 36A1, the P30 Cancer Center Support Grant P30 CA014236, and the Endocrine Fellows Foundation Marilyn Fishman Grant for Endocrinology Research, Spring 2015 cycle.


Julie A. Sosa is a member of the Data Monitoring Committee of the Medullary Thyroid Cancer Consortium Registry supported by NovoNordisk, GlaxoSmithKline, Astra Zeneca, and Eli Lilly. Ewa Ruel, Samantha Thomas, Jennifer M. Perkins, and Sanziana A. Roman have no disclosures to declare.


  1. 1.
    DeSantis CE, Lin CC, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64(4):252–71.CrossRefPubMedGoogle Scholar
  2. 2.
    Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26(1):1–133.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Randolph GW, Duh QY, Heller KS, et al. The prognostic significance of nodal metastases from papillary thyroid carcinoma can be stratified based on the size and number of metastatic lymph nodes, as well as the presence of extranodal extension. Thyroid. 2012;22(11):1144–52.CrossRefPubMedGoogle Scholar
  4. 4.
    Ricarte-Filho J, Ganly I, Rivera M, et al. Papillary thyroid carcinomas with cervical lymph node metastases can be stratified into clinically relevant prognostic categories using oncogenic BRAF, the number of nodal metastases, and extra-nodal extension. Thyroid. 2012;22(6):575–84.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    de Carvalho AY, Chulam TC, Kowalski LP. Long-term results of observation vs prophylactic selective level VI neck dissection for papillary thyroid carcinoma at a cancer center. JAMA Otolaryngol Head Neck Surg. 2015;141(7):599–606.CrossRefGoogle Scholar
  6. 6.
    Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging manual. 7th ed. New York, NY: Springer; 2010.Google Scholar
  7. 7.
    Mazzaferri EL, Doherty GM, Steward DL. The pros and cons of prophylactic central compartment lymph node dissection for papillary thyroid carcinoma. Thyroid. 2009;19(7):683–89.CrossRefPubMedGoogle Scholar
  8. 8.
    Conzo G, Calo PG, Sinisi AA, et al. Impact of prophylactic central compartment neck dissection on locoregional recurrence of differentiated thyroid cancer in clinically node-negative patients: a retrospective study of a large clinical series. Surgery. 2014;155(6):998–1005.CrossRefPubMedGoogle Scholar
  9. 9.
    Wada N, Duh QY, Sugino K, et al. Lymph node metastasis from 259 papillary thyroid microcarcinomas: frequency, pattern of occurrence and recurrence, and optimal strategy for neck dissection. Ann Surg. 2003;237(3):399–407.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Bilimoria KY, Stewart AK, Winchester DP, Ko CY. The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol. 2008;15(3):683–90.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Phillips JK, Stewart AK, editors. Facility oncology data standards. Chicago, IL: Commission on Cancer; 2006.Google Scholar
  12. 12.
    Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992;45(6):613–19.CrossRefPubMedGoogle Scholar
  13. 13.
    Commission on Cancer, American Cancer Society. National Cancer Data Base PUF. NCDB Participant User File, American College of Surgeons 2012. Accessed 29 May 2015.
  14. 14.
    Bonnet S, Hartl D, Leboulleux S, et al. Prophylactic lymph node dissection for papillary thyroid cancer less than 2 cm: implications for radioiodine treatment. J Clin Endocrinol Metab. 2009;94(4):1162–67.CrossRefPubMedGoogle Scholar
  15. 15.
    Lang BH, Wong KP, Wan KY, Lo CY. Impact of routine unilateral central neck dissection on preablative and postablative stimulated thyroglobulin levels after total thyroidectomy in papillary thyroid carcinoma. Ann Surg Oncol. 2012;19(1):60–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Barczynski M, Konturek A, Stopa M, Nowak W. Prophylactic central neck dissection for papillary thyroid cancer. Br J Surg. 2013;100(3):410–18.CrossRefPubMedGoogle Scholar
  17. 17.
    Carty SE, Cooper DS, Doherty GM, et al. Consensus statement on the terminology and classification of central neck dissection for thyroid cancer. Thyroid. 2009;19(11):1153–58.CrossRefPubMedGoogle Scholar
  18. 18.
    Ahn BH, Kim JR, Jeong HC, Lee JS, Chang ES, Kim YH. Predictive factors of central lymph node metastasis in papillary thyroid carcinoma. Ann Surg Treat Res. 2015;88(2):63–8.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Eun YG, Lee YC, Kwon KH. Predictive factors of contralateral paratracheal lymph node metastasis in papillary thyroid cancer: prospective multicenter study. Otolaryngol Head Neck Surg. 2014;150(2):210–15.CrossRefPubMedGoogle Scholar
  20. 20.
    Wu MH, Shen WT, Gosnell J, Duh QY. Prognostic significance of extranodal extension of regional lymph node metastasis in papillary thyroid cancer. Head Neck. 2015;37(9):1336–43.CrossRefPubMedGoogle Scholar
  21. 21.
    Suh YJ, Kwon H, Kim SJ, et al. Factors affecting the locoregional recurrence of conventional papillary thyroid carcinoma after surgery: a retrospective analysis of 3381 patients. Ann Surg Oncol. 2015;22(11):3543–49.CrossRefPubMedGoogle Scholar
  22. 22.
    Leboulleux S, Rubino C, Baudin E, et al. Prognostic factors for persistent or recurrent disease of papillary thyroid carcinoma with neck lymph node metastases and/or tumor extension beyond the thyroid capsule at initial diagnosis. J Clin Endocrinol Metab. 2005;90(10):5723–29.CrossRefPubMedGoogle Scholar
  23. 23.
    Xiao GZ, Gao L. Central lymph node metastasis: is it a reliable indicator of lateral node involvement in papillary thyroid carcinoma? World J Surg. 2010;34(2):237–41.CrossRefPubMedGoogle Scholar
  24. 24.
    Sugitani I, Kasai N, Fujimoto Y, Yanagisawa A. A novel classification system for patients with PTC: addition of the new variables of large (3 cm or greater) nodal metastases and reclassification during the follow-up period. Surgery. 2004;135(2):139–48.CrossRefPubMedGoogle Scholar
  25. 25.
    Ruel E, Thomas S, Dinan M, Perkins JM, Roman SA, Sosa JA. Adjuvant radioactive iodine therapy is associated with improved survival for patients with intermediate-risk papillary thyroid cancer. J Clin Endocrinol Metab. 2015;100(4):1529–36.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Adam MA, Pura J, Goffredo P, et al. Presence and number of lymph node metastases are associated with compromised survival for patients younger than age 45 years with papillary thyroid cancer. J Clin Oncol. 2015;33(21):2370–75.CrossRefPubMedGoogle Scholar
  27. 27.
    Carling T, Carty SE, Ciarleglio MM, 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;22(3):237–44.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2017

Authors and Affiliations

  • Ewa Ruel
    • 1
  • Samantha Thomas
    • 2
    • 3
  • Jennifer M. Perkins
    • 1
  • Sanziana A. Roman
    • 3
    • 4
  • Julie A. Sosa
    • 3
    • 4
    • 5
    • 6
  1. 1.Department of Medicine (Endocrinology, Metabolism and Nutrition)Duke University Medical CenterDurhamUSA
  2. 2.Department of Biostatistics and BioinformaticsDuke UniversityDurhamUSA
  3. 3.Duke Cancer InstituteDurhamUSA
  4. 4.Section of Endocrine Surgery, Department of SurgeryDuke University Medical CenterDurhamUSA
  5. 5.Duke Clinical Research InstituteDurhamUSA
  6. 6.Department of Medicine (Oncology)Duke University Medical CenterDurhamUSA

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