Can patients with papillary thyroid carcinoma and low postoperative thyroglobulin in the presence of clinically apparent lymph node metastases (cN1) be spared from radioiodine?

Abstract

Background

The study evaluated the recurrence rate in patients with papillary thyroid carcinoma (PTC) and clinically apparent lymph node metastases (LNM) (cN1) who had low thyroglobulin (Tg) after total thyroidectomy and who were not submitted to adjuvant therapy with 131I.

Methods

This was a prospective study. It included 82 cN1 patients (≤3 LNM ≤1.5 cm without macroscopic extracapsular extension) with tumors ≤4 cm without macroscopic extrathyroid invasion (T1–2) and who after thyroidectomy had unstimulated Tg (u-Tg) < 0.3 ng/ml, negative antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) showing no anomalies. The patients were not submitted to therapy with 131I.

Results

The time of follow-up ranged from 24 to 156 months (median 84 months). Seventy-nine patients (96.3%) continued to have u-Tg < 0.3 ng/ml and negative US. Three patients (3.6%) exhibited an increase in Tg and structural recurrence was detected in two. After treatment, these patients achieved u-Tg < 1 ng/ml and the imaging methods revealed no apparent tumor.

Conclusions

The results suggest that even cN1 patients, given the absence of extensive LNM or other adverse findings, who have low Tg and neck US showing no anomalies after thyroidectomy do not require radioiodine.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    G.W. Randolph, Q.Y. Duh, K.S. Heller, V.A. LiVolsi, S.J. Mandel, D.L. Steward, R.P. Tufano, R.M. Tuttle, American Thyroid Association Surgical Affairs Committee’s Taskforce on Thyroid Cancer Nodal Surgery. 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 22, 1144–1152 (2012)

    Article  Google Scholar 

  2. 2.

    B.R. Haugen, E.K. Alexander, K.C. Bible, G.M. Doherty, S.J. Mandel, Y.E. Nikiforov, F. Pacini, G.W. Randolph, A.M. Sawka, M. Schlumberger, K.G. Schuff, S.I. Sherman, J.A. Sosa, D.L. Steward, R.M. Tuttle, L. Wartofsky, 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 26, 1–133 (2016)

    Article  Google Scholar 

  3. 3.

    A.L. Mitchell, A. Gandhi, D. Scott-Coombes, P. Perros, Management of thyroid cancer: United Kingdom National Multidisciplinary Guidelines. J. Laryngol. Otol. 130, S150–S160 (2016)

    CAS  Article  Google Scholar 

  4. 4.

    S. Zerdoud, A.L. Giraudet, S. Leboulleux, L. Leenhardt, S. Bardet, J. Clerc, M.E. Toubert, A. Al Ghuzlan, P.J. Lamy, C. Bournaud, I. Keller, F. Sebag, R. Garrel, E. Mirallié, L. Groussin, E. Hindié, D. Taïeb, Radioactive iodine therapy, molecular imaging and serum biomarkers for differentiated thyroid cancer: 2017 guidelines of the French Societies of Nuclear Medicine, Endocrinology, Pathology, Biology, Endocrine Surgery and Head and Neck Surgery. Ann. Endocrinol. 78, 162–175 (2017)

    Article  Google Scholar 

  5. 5.

    F. Pacini, F. Basolo, R. Bellantone, G. Boni, M.A. Cannizzaro, M. De Palma, C. Durante, R. Elisei, G. Fadda, A. Frasoldati, L. Fugazzola, R. Guglielmi, C.P. Lombardi, P. Miccoli, E. Papini, G. Pellegriti, L. Pezzullo, A. Pontecorvi, M. Salvatori, E. Seregni, P. Vitti, Italian consensus on diagnosis and treatment of differentiated thyroid cancer: joint statements of six Italian societies. J. Endocrinol. Investig. 41, 849–876 (2018)

    CAS  Article  Google Scholar 

  6. 6.

    S. Filetti, C. Durante, D. Hartl, S. Leboulleux, L.D. Locati, K. Newbold, M.G. Papotti, A. Berruti; ESMO Guidelines Committee, Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 20, 1856–1883 (2019)

    Article  Google Scholar 

  7. 7.

    C. Lepoutre-Lussey, D. Deandreis, S. Leboulleux, M. Schlumberger, Postoperative radioactive iodine administration for differentiated thyroid cancer patients. Curr. Opin. Endocrinol. Diabetes Obes. 21, 363–371 (2014)

    CAS  Article  Google Scholar 

  8. 8.

    K.M. Creach, B.A. Siegel, B. Nussenbaum, P.W. Grigsby, Radioactive iodine therapy decreases recurrence in thyroid papillary microcarcinoma. ISRN Endocrinol. 2012, 816386 (2012)

    Article  Google Scholar 

  9. 9.

    S. Xue, P. Wang, J. Liu, G. Chen, Radioactive iodine ablation decrease recurrences in papillary thyroid microcarcinoma with lateral lymph node metastasis in Chinese patients. World J. Surg. 41, 3149–3146 (2017)

    Article  Google Scholar 

  10. 10.

    T. Yang, S.Y. Zheng, J. Jiao, Q. Zou, Y. Zhang, Radioiodine remnant ablation in papillary thyroid microcarcinoma: a meta-analysis. Nucl. Med. Commun. 40, 711–719 (2019)

    Article  Google Scholar 

  11. 11.

    F.A. Verburg, G. Flux, L. Giovanella, D. van Nostrand, K. Muylle, M. Luster, Differentiated thyroid cancer patients potentially benefitting from postoperative I-131 therapy: a review of the literature of the past decade. Eur. J. Nucl. Med. Mol. Imaging 47, 78–83 (2020)

    CAS  Article  Google Scholar 

  12. 12.

    National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in oncology: thyroid carcinoma version 2. 2019. http://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf. Accessed 10 May 2020

  13. 13.

    F.A. Verburg, U. Mäder, C. Reiners, H. Hänscheid, Long-term survival in differentiated thyroid cancer is worse after low-activity initial post-surgical 131I therapy in both high- and low-risk patients. J. Clin. Endocrinol. Metab. 99, 4487–4496 (2014)

    CAS  Article  Google Scholar 

  14. 14.

    K.P. Chu, S. Baker, J. Zenke, A. Morad, S. Ghosh, D.W. Morrish, A.J.B. McEwan, D.C. Willians, D. Severin, T.P.W. McMullen, Low activity radioactive iodine therapy for thyroid carcinomas exhibiting nodal metastases and extrathyroidal extension may lead to early disease recurrence. Thyroid 28, 902–912 (2018)

    CAS  Article  Google Scholar 

  15. 15.

    M. Luster, C. Aktolun, I. Amendoeira, M. Barczyński, K.C. Bible, L.H. Duntas, R. Elisei, D. Handkiewicz-Junak, M. Hoffmann, B. Jarzab, L. Leenhardt, T. Musholt, K. Newbold, I.J. Nixon, J. Smit, M. Sobrinho–Simões, J.A. Sosa, R.M. Tuttle, F. Verburg, L. Wartofsky, D. Führer-Sakel, European perspective on the 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Proceedings of an interactive international symposium. Thyroid 29, 7–26 (2018)

    Article  Google Scholar 

  16. 16.

    D. Ylli, D. Van Nostrand, L. Wartofsky, Conventional radioiodine therapy for differentiated thyroid cancer. Endocrinol. Metab. Clin. North Am. 48, 181–197 (2019)

    Article  Google Scholar 

  17. 17.

    A. Vaisman, S. Orlov, J. Yip, C. Hu, T. Lim, M. Dowar, J.L. Freeman, P.G. Walfish, Application of post-surgical stimulated thyroglobulin for radioiodine remnant ablation selection in low-risk papillary thyroid carcinoma. Head Neck. 32, 689–698 (2010)

    PubMed  Google Scholar 

  18. 18.

    T. Ibrahimpasic, I.J. Nixon, F.L. Palmer, M.M. Whitcher, R.M. Tuttle, A. Shaha, S.G. Patel, J.P. Shah, I. Ganly, Undetectable thyroglobulin after total thyroidectomy in patients with low- and intermediate-risk papillary thyroid cancer–is there a need for radioactive iodine therapy? Surgery 152, 1096–1105 (2012)

    Article  Google Scholar 

  19. 19.

    S. Orlov, F. Salari, L. Kashat, J.L. Freeman, A. Vescan, I.J. Witterick, P.G. Walfish, Post-operative stimulated thyroglobulin and neck ultrasound as personalized criteria for risk stratification and radioactive iodine selection in low- and intermediate-risk papillary thyroid cancer. Endocrine 50, 130–137 (2015)

    CAS  Article  Google Scholar 

  20. 20.

    D.P. Momesso, F. Vaisman, S.P. Yang, D.A. Bulzico, R. Corbo, M. Vaisman, R.M. Tuttle, Dynamic risk stratification in patients with differentiated thyroid cancer treated without radioactive iodine. J. Clin. Endocrinol. Metab. 101, 2692–2700 (2016)

    CAS  Article  Google Scholar 

  21. 21.

    L.F. Zavala, M.I. Barra, R. Olmos, M. Tuttle, H. González, N. Droppelmann, L. Mosso, J.M. Domínguez, In properly selected patients with differentiated thyroid cancer, antithyroglobulin antibodies decline after thyroidectomy and their sole presence should not be an indication for radioiodine ablation. Arch. Endocrinol. Metab. 63, 293–299 (2019)

    PubMed  Google Scholar 

  22. 22.

    A.D. McDow, C.M. Shumway, S.C. Pitt, D.F. Schneider, R.S. Sippel, K.L. Long, Utility of early postoperative unstimulated thyroglobulin in influencing decision making in patients with papillary thyroid carcinoma. Ann. Surg. Oncol. 26, 4002–4007 (2019)

    Article  Google Scholar 

  23. 23.

    G.F. Mourão, P.W. Rosario, M.R. Calsolari, Low postoperative nonstimulated thyroglobulin as a criterion to spare radioiodine ablation. Endocr. Relat. Cancer 23, 47–52 (2016)

    Article  Google Scholar 

  24. 24.

    P.W. Rosario, G.F. Mourão, M.R. Calsolari, Low postoperative nonstimulated thyroglobulin as a criterion for the indication of low radioiodine activity in patients with papillary thyroid cancer of intermediate risk ‘with higher risk features’. Clin. Endocrinol. 85, 453–458 (2016)

    CAS  Article  Google Scholar 

  25. 25.

    P.W. Rosario, G.F. Mourão, M.R. Calsolari, Long-term results of ablation with low radioiodine activity in patients with papillary thyroid carcinoma and predictive value of postoperative nonstimulated thyroglobulin. Nucl. Med. Commun. 37, 1024–1029 (2016)

    CAS  Article  Google Scholar 

  26. 26.

    P.W. Rosario, G.F. Mourão, M.R. Calsolari, Efficacy of adjuvant therapy with 3.7 GBq radioactive iodine in intermediate-risk patients with ‘higher risk features’ and predictive value of postoperative nonstimulated thyroglobulin. Nucl. Med. Commun. 37, 1148–1153 (2006)

    Article  Google Scholar 

  27. 27.

    P.W. Rosario, S. de Faria, L. Bicalho, M.F. Alves, M.A. Borges, S. Purisch, E.L. Padrão, L.L. Rezende, A.L. Barroso, Ultrasonographic differentiation between metastatic and benign lymph nodes in patients with papillary thyroid carcinoma. J. Ultrasound Med. 24, 1385–1389 (2005)

    Article  Google Scholar 

  28. 28.

    P.W. Rosario, W.C. Tavares, M.A. Borges, J.B. Santos, M.R. Calsolari, Ultrasonographic differentiation of cervical lymph nodes in patients with papillary thyroid carcinoma after thyroidectomy and radioiodine ablation: a prospective study. Endocr. Pract. 20, 293–298 (2014)

    Article  Google Scholar 

  29. 29.

    P.W. Rosario, G.F. Mourão, T.L. Siman, M.R. Calsolari, Serum Thyroglobulin measured with a second-generation assay in patients undergoing total thyroidectomy without radioiodine remnant ablation: a prospective study. Thyroid 25, 769–775 (2015)

    CAS  Article  Google Scholar 

  30. 30.

    M. Tuttle, L.F. Morris, B. Haugen, J. Shah, J.A. Sosa, E. Rohren, R.M. Subramaniam, J.L. Hunt, N.D. Perrier, in Thyroid—Differentiated and Anaplastic Carcinoma (Chapter 73). ed. by M.B. Amin, S.B. Edge, F. Greene, D. Byrd, R.K. Brookland, M.K. Washington, J.E. Gershenwald, C.C. Compton, K.R. Hess, D.C. Sullivan, J.M. Jessup, J. Brierley, L.E. Gaspar, R.L. Schilsky, C.M. Balch, D.P. Winchester, E.A. Asare, M. Madera, D.M. Gress, L.R. Meyer, AJCC Cancer Staging Manual. 8th edn. (Springer International Publishing, New York City, 2017)

  31. 31.

    P.W. Rosario, G.F. Mourão, J.B. dos Santos, M.R. Calsolari, Is empirical radioactive iodine therapy still a valid approach to patients with thyroid cancer and elevated thyroglobulin? Thyroid 24, 533–536 (2014)

    CAS  Article  Google Scholar 

  32. 32.

    S. Bardet, R. Ciappuccini, E. Quak, J.P. Rame, D. Blanchard, D. de Raucourt, E. Babin, J.J. Michels, D. Vaur, N. Heutte, Prognostic value of microscopic lymph node involvement in patients with papillary thyroid cancer. J. Clin. Endocrinol. Metab. 100, 132–140 (2015)

    CAS  Article  Google Scholar 

  33. 33.

    L. Giovanella, L. Ceriani, S. Suriano, A. Ghelfo, M. Maffioli, Thyroglobulin measurement before rhTSH-aided 131I ablation in detecting metastases from differentiated thyroid carcinoma. Clin. Endocrinol. 69, 659–663 (2008)

    CAS  Article  Google Scholar 

  34. 34.

    A. Matrone, C. Gambale, P. Piaggi, D. Viola, C. Giani, L. Agate, V. Bottici, F. Bianchi, G. Materazzi, P. Vitti, E. Molinaro, R. Elisei, Postoperative thyroglobulin and neck ultrasound in the risk restratification and decision to perform 131I ablation. J. Clin. Endocrinol. Metab. 102, 893–902 (2017)

    PubMed  Google Scholar 

  35. 35.

    E. Robenshtok, R.K. Grewal, S. Fish, M. Sabra, R.M. Tuttle, A low postoperative nonstimulated serum thyroglobulin level does not exclude the presence of radioactive iodine avid metastatic foci in intermediate-risk differentiated thyroid cancer patients. Thyroid 23, 436–442 (2013)

    CAS  Article  Google Scholar 

  36. 36.

    A. Matrone, C. Gambale, L. Torregrossa, P. Piaggi, F. Bianchi, L. Valerio, D. Viola, L. Agate, E. Molinaro, G. Materazzi, F. Basolo, P. Vitti, R. Elisei, Delayed 131-I first treatment after surgery has no impact on the median term outcome of patients with intermediate risk differentiated thyroid cancer. Endocr. Pract. 26, 58–71 (2020)

    Article  Google Scholar 

  37. 37.

    R.S. Scheffel, A.B. Zanella, J.M. Dora, A.L. Maia, Timing of radioactive iodine administration does not influence outcomes in patients with differentiated thyroid carcinoma. Thyroid 26, 1623–1629 (2016)

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Council for Scientific and Technological Development (CNPq).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Pedro Weslley Rosario.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Research Ethics Committee of our institution.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Rosario, P.W., Mourão, G.F. & Calsolari, M.R. Can patients with papillary thyroid carcinoma and low postoperative thyroglobulin in the presence of clinically apparent lymph node metastases (cN1) be spared from radioiodine?. Endocrine 70, 552–557 (2020). https://doi.org/10.1007/s12020-020-02414-1

Download citation

Keywords

  • Papillary Thyroid Carcinoma
  • Lymph Node Metastases
  • Postoperative Nonstimulated Thyroglobulin
  • Radioiodine