Knowledge of pathologically versus clinically negative lymph nodes is associated with reduced use of radioactive iodine post-thyroidectomy for low-risk papillary thyroid cancer
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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.
KeywordsPapillary thyroid cancer Prophylactic lymph node dissection Radioactive iodine Cervical lymph node metastasis NCDB
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.
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Conflict of interest
The authors declare no conflict of interest. The data used in the study are derived from a de-identified National Cancer Data Base (NCDB) file. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology employed, or the conclusions drawn from these data by the investigators.
- 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
- 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.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.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.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
- 9.J.K.S.A. Phillips (ed.), Facility Oncology Data Standards (Commission on Cancer, Chicago, 2006)Google Scholar
- 11.Commission on Cancer, American Cancer Society. National Cancer Data Base PUF. http://ncdbpuf.facs.org. Accessed 29 May 2015
- 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
- 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
- 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.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
- 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.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
- 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