Endocrine

, Volume 52, Issue 3, pp 579–586 | Cite as

Knowledge of pathologically versus clinically negative lymph nodes is associated with reduced use of radioactive iodine post-thyroidectomy for low-risk papillary thyroid cancer

  • Ewa Ruel
  • Samantha Thomas
  • Michaela A. Dinan
  • Jennifer M. Perkins
  • Sanziana A. Roman
  • Julie Ann Sosa
Original Article

Abstract

Cervical lymph node metastases are common in papillary thyroid cancer (PTC). Clinically negative lymph nodes confer uncertainty about true lymph node status, potentially prompting empiric postoperative radioactive iodine (RAI) administration even in low-risk patients. We examined the association of clinically (cN0) versus pathologically negative (pN0) lymph nodes with utilization of RAI for low-risk PTC. Using the National Cancer Database 1998–2011, adults with PTC who underwent total thyroidectomy for Stage I/II tumors 1–4 cm were evaluated for receipt of RAI based on cN0 versus pN0 status. Cut-point analysis was conducted to determine the number of pN0 nodes associated with the greatest decrease in the odds of receipt of RAI. Survival models and multivariate analyses predicting RAI use were conducted separately for all patients and patients <45 years. 64,980 patients met study criteria; 39,778 (61.2 %) were cN0 versus 25,202 (38.8 %) pN0. Patients with pN0 nodes were more likely to have negative surgical margins and multifocal disease (all p < 0.001). The mean negative nodes reported in surgical pathology specimens was 4; ≥5 pathologically negative lymph nodes provided the best cut-point associated with reduced RAI administration (OR 0.91, CI 0.85–0.97). After multivariable adjustment, pN0 patients with ≥5 nodes examined were less likely to receive RAI compared to cN0 patients across all ages (OR 0.89, p < 0.001) and for patients aged <45 years (0R 0.86, p = 0.001). Patients with <5 pN0 nodes did not differ in RAI use compared to cN0 controls. Unadjusted survival was improved for pN0 versus cN0 patients across all ages (p < 0.001), but not for patients <45 years (p = 0.11); adjusted survival for all ages did not differ (p = 0.13). Pathological confirmation of negative lymph nodes in patients with PTC appears to influence the decision to administer postoperative RAI if ≥5 negative lymph nodes are removed. It is possible that fewer excised lymph nodes may be viewed by clinicians as incidentally resected and thus may suboptimally represent the true nodal status of the central neck. Further research is warranted to determine if there is an optimal number of lymph nodes that should be resected to standardize pathological diagnosis.

Keywords

Papillary thyroid cancer Prophylactic lymph node dissection Radioactive iodine Cervical lymph node metastasis NCDB 

References

  1. 1.
    E.L. Mazzaferri, G.M. Doherty, D.L. Steward, The pros and cons of prophylactic central compartment lymph node dissection for papillary thyroid carcinoma. Thyroid 19, 683–689 (2009)CrossRefPubMedGoogle Scholar
  2. 2.
    G. Conzo, P.G. Calo, A.A. Sinisi, A. De Bellis, D. Pasquali, S. Iorio, E. Tartaglia, C. Mauriello, C. Gambardella, F. Cavallo, F. Medas, A. Polistena, L. Santini, N. Avenia, 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 155, 998–1005 (2014)CrossRefPubMedGoogle Scholar
  3. 3.
    F. Arturi, D. Russo, D. Giuffrida, A. Ippolito, N. Perrotti, R. Vigneri, S. Filetti, Early diagnosis by genetic analysis of differentiated thyroid cancer metastases in small lymph nodes. J. Clin. Endocrinol. Metab. 82, 1638–1641 (1997)CrossRefPubMedGoogle Scholar
  4. 4.
    D.S. Cooper, G.M. Doherty, B.R. Haugen, R.T. Kloos, S.L. Lee, S.J. Mandel, E.L. Mazzaferri, B. McIver, F. Pacini, M. Schlumberger, S.I. Sherman, D.L. Steward, R.M. Tuttle, Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19, 1167–1214 (2009)CrossRefPubMedGoogle Scholar
  5. 5.
    S. Bonnet, D. Hartl, S. Leboulleux, E. Baudin, J.D. Lumbroso, A. Al Ghuzlan, L. Chami, M. Schlumberger, J.P. Travagli, Prophylactic lymph node dissection for papillary thyroid cancer less than 2 cm: implications for radioiodine treatment. J. Clin. Endocrinol. Metab. 94, 1162–1167 (2009)CrossRefPubMedGoogle Scholar
  6. 6.
    D.T. Hughes, M.L. White, B.S. Miller, P.G. Gauger, R.E. Burney, G.M. Doherty, Influence of prophylactic central lymph node dissection on postoperative thyroglobulin levels and radioiodine treatment in papillary thyroid cancer. Surgery 148, 1100–1106 (2010). discussion 1006–1107 CrossRefPubMedGoogle Scholar
  7. 7.
    D. Viola, G. Materazzi, L. Valerio, E. Molinaro, L. Agate, P. Faviana, V. Seccia, E. Sensi, C. Romei, P. Piaggi, L. Torregrossa, S. Sellari-Franceschini, F. Basolo, P. Vitti, R. Elisei, P. Miccoli, Prophylactic central compartment lymph node dissection in papillary thyroid carcinoma: clinical implications derived from the first prospective randomized controlled single institution study. J. Clin. Endocrinol. Metab. 100, 1316–1324 (2015)CrossRefPubMedGoogle Scholar
  8. 8.
    K.Y. Bilimoria, A.K. Stewart, D.P. Winchester, C.Y. Ko, The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann. Surg. Oncol. 15, 683–690 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    J.K.S.A. Phillips (ed.), Facility Oncology Data Standards (Commission on Cancer, Chicago, 2006)Google Scholar
  10. 10.
    R.A. Deyo, D.C. Cherkin, M.A. Ciol, Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J. Clin. Epidemiol. 45, 613–619 (1992)CrossRefPubMedGoogle Scholar
  11. 11.
    Commission on Cancer, American Cancer Society. National Cancer Data Base PUF. http://ncdbpuf.facs.org. Accessed 29 May 2015
  12. 12.
    B.A. Williams, J.N. Mandrekar, S.J. Mandrekar, S.S. Cha, A.F. Furth, Finding Optimal Cutpoints for Continuous Covariates with Binary and Time-to-Event Outcomes. Technical Report Series #79, 2006. http://www.mayo.edu/research/documents/biostat-79pdf/doc-10027230
  13. 13.
    B.H. Lang, K.P. Wong, K.Y. Wan, C.Y. Lo, Impact of routine unilateral central neck dissection on preablative and postablative stimulated thyroglobulin levels after total thyroidectomy in papillary thyroid carcinoma. Ann. Surg. Oncol. 19, 60–67 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    M. Barczynski, A. Konturek, M. Stopa, W. Nowak, Prophylactic central neck dissection for papillary thyroid cancer. Br. J. Surg. 100, 410–418 (2013)CrossRefPubMedGoogle Scholar
  15. 15.
    Y.D. Podnos, D.D. Smith, L.D. Wagman, J.D. Ellenhorn, Survival in patients with papillary thyroid cancer is not affected by the use of radioactive isotope. J. Surg. Oncol. 96, 3–7 (2007)CrossRefPubMedGoogle Scholar
  16. 16.
    J. Jonklaas, N.J. Sarlis, D. Litofsky, K.B. Ain, S.T. Bigos, J.D. Brierley, D.S. Cooper, B.R. Haugen, P.W. Ladenson, J. Magner, J. Robbins, D.S. Ross, M. Skarulis, H.R. Maxon, S.I. Sherman, Outcomes of patients with differentiated thyroid carcinoma following initial therapy. Thyroid 16, 1229–1242 (2006)CrossRefPubMedGoogle Scholar
  17. 17.
    J. Jonklaas, D.S. Cooper, K.B. Ain, T. Bigos, J.D. Brierley, B.R. Haugen, P.W. Ladenson, J. Magner, D.S. Ross, M.C. Skarulis, D.L. Steward, H.R. Maxon, S.I. Sherman, Radioiodine therapy in patients with stage I differentiated thyroid cancer. Thyroid 20, 1423–1424 (2010)CrossRefPubMedGoogle Scholar
  18. 18.
    S. Edge, D.R. Byrd, C.C. Compton, A.G. Fritz, F.L. Greene, A. Trotti, AJCC Cancer Staging Manual, 7th edn. (Springer, New York, 2010)Google Scholar
  19. 19.
    S.E. Carty, D.S. Cooper, G.M. Doherty, Q.Y. Duh, R.T. Kloos, S.J. Mandel, G.W. Randolph, B.C. Stack Jr, D.L. Steward, D.J. Terris, G.B. Thompson, R.P. Tufano, R.M. Tuttle, R. Udelsman, Consensus statement on the terminology and classification of central neck dissection for thyroid cancer. Thyroid 19, 1153–1158 (2009)CrossRefPubMedGoogle Scholar
  20. 20.
    B.H. Ahn, J.R. Kim, H.C. Jeong, J.S. Lee, E.S. Chang, Y.H. Kim, Predictive factors of central lymph node metastasis in papillary thyroid carcinoma. Ann. Surg. Treat. Res. 88, 63–68 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Y.G. Eun, Y.C. Lee, K.H. Kwon, Predictive factors of contralateral paratracheal lymph node metastasis in papillary thyroid cancer: prospective multicenter study. Otolaryngol. Head Neck Surg. 150, 210–215 (2014)CrossRefPubMedGoogle Scholar
  22. 22.
    C.W. Lee, G. Gong, J.L. Roh, Intraoperative diagnosis of central compartment lymph node metastasis predicts recurrence of patients with papillary thyroid carcinoma and clinically node-negative lateral neck and may guide extent of initial surgery. World J. Surg. 39, 194–202 (2015)CrossRefPubMedGoogle Scholar
  23. 23.
    M. Raffaelli, C. De Crea, L. Sessa, P. Giustacchini, L. Revelli, C. Bellantone, C.P. Lombardi, Prospective evaluation of total thyroidectomy versus ipsilateral versus bilateral central neck dissection in patients with clinically node-negative papillary thyroid carcinoma. Surgery 152, 957–964 (2012)CrossRefPubMedGoogle Scholar
  24. 24.
    V. Zaydfudim, I.D. Feurer, M.R. Griffin, J.E. Phay, The impact of lymph node involvement on survival in patients with papillary and follicular thyroid carcinoma. Surgery 144, 1070–1077 (2008). discussion 1077–1078 CrossRefPubMedGoogle Scholar
  25. 25.
    T.S. Wang, K. Cheung, F. Farrokhyar, S.A. Roman, J.A. Sosa, A meta-analysis of the effect of prophylactic central compartment neck dissection on locoregional recurrence rates in patients with papillary thyroid cancer. Ann. Surg. Oncol. 20, 3477–3483 (2013)CrossRefPubMedGoogle Scholar
  26. 26.
    D.M. Hartl, E. Mamelle, I. Borget, S. Leboulleux, H. Mirghani, M. Schlumberger, Influence of prophylactic neck dissection on rate of retreatment for papillary thyroid carcinoma. World J. Surg. 37, 1951–1958 (2013)CrossRefPubMedGoogle Scholar
  27. 27.
    D. Giordano, R. Valcavi, G.B. Thompson, C. Pedroni, L. Renna, P. Gradoni, V. Barbieri, Complications of central neck dissection in patients with papillary thyroid carcinoma: results of a study on 1087 patients and review of the literature. Thyroid 22, 911–917 (2012)CrossRefPubMedGoogle Scholar
  28. 28.
    L. Davies, H.G. Welch, Thyroid cancer survival in the United States: observational data from 1973 to 2005. Arch. Otolaryngol. Head Neck Surg. 136, 440–444 (2010)CrossRefPubMedGoogle Scholar
  29. 29.
    T. Carling, S.E. Carty, M.M. Ciarleglio, D.S. Cooper, G.M. Doherty, L.T. Kim, R.T. Kloos, E.L. Mazzaferri Sr, P.N. Peduzzi, S.A. Roman, R.S. Sippel, J.A. Sosa, B.C. Stack Jr, D.L. Steward, R.P. Tufano, R.M. Tuttle, R. Udelsman, American Thyroid Association design and feasibility of a prospective randomized controlled trial of prophylactic central lymph node dissection for papillary thyroid carcinoma. Thyroid 22, 237–244 (2012)CrossRefPubMedGoogle Scholar
  30. 30.
    M.V. Raval, K.Y. Bilimoria, A.K. Stewart, D.J. Bentrem, C.Y. Ko, Using the NCDB for cancer care improvement: an introduction to available quality assessment tools. J. Surg. Oncol. 99, 488–490 (2009)CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Division of Endocrinology, Metabolism and Nutrition, Department of MedicineDuke University Medical CenterDurhamUSA
  2. 2.Department of Biostatistics and BioinformaticsDuke University School of MedicineDurhamUSA
  3. 3.Duke Clinical Research InstituteDuke UniversityDurhamUSA
  4. 4.Section of Endocrine Surgery, Department of SurgeryDuke University Medical CenterDurhamUSA
  5. 5.Duke Cancer InstituteDurhamUSA

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