Skip to main content
Log in

Long-term clinical outcomes and prognostic factors for patients with papillary thyroid carcinoma with other organ invasions after adjuvant radioactive iodine

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript



Papillary thyroid carcinoma (PTC) with other organ invasions is directly related to patient prognosis and quality of life; however, studies on the clinical outcomes of adjuvant radioactive iodine (RAI) for PTC with other organ invasions are limited. This study aimed to clarify the clinical outcomes and prognostic factors for patients with PTC with other organ invasions after adjuvant RAI.


Patients with PTC with other organ invasions without distant metastases who underwent surgery and adjuvant RAI were retrospectively reviewed. We evaluated the initial responses based on the American Thyroid Association guidelines and survival rates. Prognostic factors for locoregional recurrence-free survival (LRRFS) were analyzed.


Between January 2005 and December 2019, 102 patients were included in the study. Their median age was 55 years. The median follow-up duration was 92 months (range; 30–231 months). The excellent response rate after RAI was 42%. The 7-year overall survival, LRRFS, and recurrence-free survival rates were 100%, 75%, and 75%, respectively. Metastatic lymph node size, resection margin status, and post-RAI suppressed thyroglobulin level were the independent prognostic factors for LRRFS.


We demonstrated that 75% of patients with PTC with other organ invasions could achieve long-term survival without recurrence after adjuvant RAI. Future development of effective treatment strategies for large metastatic lymph nodes, gross residual tumors, and high serum thyroglobulin levels is warranted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Data availability

Raw data of this analysis are available from the corresponding author upon request.



American Thyroid Association


confidence interval


computed tomography


external-beam radiotherapy


extra-capsular extension


hazard ratio


locoregional recurrence-free survival


overall survival


papillary thyroid carcinoma


radioactive iodine




thyroid-stimulating hormone


  1. G. Pellegriti, F. Frasca, C. Regalbuto, S. Squatrito, R. Vigneri, Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J. Cancer Epidemiol. 2013, 965212 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  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  PubMed  PubMed Central  Google Scholar 

  3. 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)

    Article  PubMed  Google Scholar 

  4. National Comprehensive Cancer Network, Thyroid Cancer (Version 2.2022). (2022).

  5. S. Kruijff, A.M. Aniss, P. Chen, S.B. Sidhu, L.W. Delbridge, B. Robinson, R.J. Clifton-Bligh, P. Roach, A.J. Gill, D. Learoyd, M.S. Sywak, Decreasing the dose of radioiodine for remnant ablation does not increase structural recurrence rates in papillary thyroid carcinoma. Surgery 154, 1337–1344 (2013)

    Article  PubMed  Google Scholar 

  6. J.M. Han, W.G. Kim, T.Y. Kim, M.J. Jeon, J.S. Ryu, D.E. Song, S.J. Hong, Y.K. Shong, W.B. Kim, Effects of low-dose and high-dose postoperative radioiodine therapy on the clinical outcome in patients with small differentiated thyroid cancer having microscopic extrathyroidal extension. Thyroid 24, 820–825 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. M.M. Sabra, R.K. Grewal, R.A. Ghossein, R.M. Tuttle, Higher administered activities of radioactive iodine are associated with less structural persistent response in older, but not younger, papillary thyroid cancer patients with lateral neck lymph node metastases. Thyroid 24, 1088–1095 (2014)

    Article  CAS  PubMed  Google Scholar 

  8. K.D. Gray, S. Bannani, C. Caillard, S. Amanat, T.M. Ullmann, P. Romanov, L. Brunaud, T. Beninato, T.J. Fahey 3rd, E. Mirallie, R. Zarnegar, High-dose radioactive iodine therapy is associated with decreased risk of recurrence in high-risk papillary thyroid cancer. Surgery 165, 37–43 (2019)

    Article  PubMed  Google Scholar 

  9. S.Y. Jeong, S.W. Lee, W.W. Kim, J.H. Jung, W.K. Lee, B.C. Ahn, J. Lee, Clinical outcomes of patients with T4 or N1b well-differentiated thyroid cancer after different strategies of adjuvant radioiodine therapy. Sci. Rep. 9, 5570 (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  10. K. Watanabe, T. Igarashi, M. Uchiyama, H. Ojiri, Relapse-free survival after adjuvant radioactive iodine therapy in patients with differentiated thyroid carcinoma with a microscopically positive tumor margin. Ann. Nucl. Med. 34, 920–925 (2020)

    Article  CAS  PubMed  Google Scholar 

  11. K. Kim, J.S. Bae, J.S. Kim, Long-term oncological outcome comparison between intermediate- and high-dose radioactive iodine ablation in patients with differentiated thyroid carcinoma: a propensity score matching study. Int. J. Endocrinol. 2021, 6642971 (2021)

    Article  PubMed  PubMed Central  Google Scholar 

  12. M.L. Shindo, S.M. Caruana, E. Kandil, J.C. McCaffrey, L.A. Orloff, J.R. Porterfield, A. Shaha, J. Shin, D. Terris, G. Randolph, Management of invasive well-differentiated thyroid cancer: an American Head and Neck Society consensus statement. AHNS consensus statement. Head Neck 36, 1379–1390 (2014)

    PubMed  Google Scholar 

  13. S.M. Chow, S. Yau, C.K. Kwan, P.C. Poon, S.C. Law, Local and regional control in patients with papillary thyroid carcinoma: specific indications of external radiotherapy and radioactive iodine according to T and N categories in AJCC 6th edition. Endocr. Relat. Cancer 13, 1159–1172 (2006)

    Article  PubMed  Google Scholar 

  14. E.L. Mazzaferri, S.M. Jhiang, Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am. J. Med. 97, 418–428 (1994)

    Article  CAS  PubMed  Google Scholar 

  15. J. Brierley, M.K. Gospodarowicz, C. Wittekind, Tnm Classification of Malignant Tumours, 8th edn. (John Wiley & Sons, Inc., Chichester, West Sussex, UK, Hoboken, NJ, 2017)

  16. Y. Ito, N. Onoda, T. Okamoto, The revised clinical practice guidelines on the management of thyroid tumors by the Japan Associations of Endocrine Surgeons: core questions and recommendations for treatments of thyroid cancer. Endocr. J. 67, 669–717 (2020)

    Article  PubMed  Google Scholar 

  17. Y. Kanda, Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 48, 452–458 (2013)

    Article  CAS  Google Scholar 

  18. A. Sanabria, A. Rojas, J. Arevalo, L.P. Kowalski, I. Nixon, Microscopically positive surgical margins and local recurrence in thyroid cancer. A meta-analysis. Eur. J. Surg. Oncol. 45, 1310–1316 (2019)

    Article  PubMed  Google Scholar 

  19. S.A. Terezakis, K.S. Lee, R.A. Ghossein, M. Rivera, R.M. Tuttle, S.L. Wolden, M.J. Zelefsky, R.J. Wong, S.G. Patel, D.G. Pfister, A.R. Shaha, N.Y. Lee, Role of external beam radiotherapy in patients with advanced or recurrent nonanaplastic thyroid cancer: Memorial Sloan-kettering Cancer Center experience. Int. J. Radiat. Oncol. Biol. Phys. 73, 795–801 (2009)

    Article  PubMed  Google Scholar 

  20. P.B. Romesser, E.J. Sherman, A.R. Shaha, M. Lian, R.J. Wong, M. Sabra, S.S. Rao, J.A. Fagin, R.M. Tuttle, N.Y. Lee, External beam radiotherapy with or without concurrent chemotherapy in advanced or recurrent non-anaplastic non-medullary thyroid cancer. J. Surg. Oncol. 110, 375–382 (2014)

    Article  PubMed  Google Scholar 

  21. D.L. Schwartz, M.J. Lobo, K.K. Ang, W.H. Morrison, D.I. Rosenthal, A. Ahamad, D.B. Evans, G. Clayman, S.I. Sherman, A.S. Garden, Postoperative external beam radiotherapy for differentiated thyroid cancer: outcomes and morbidity with conformal treatment. Int. J. Radiat. Oncol. Biol. Phys. 74, 1083–1091 (2009)

    Article  PubMed  Google Scholar 

  22. A.P. Kiess, N. Agrawal, J.D. Brierley, U. Duvvuri, R.L. Ferris, E. Genden, R.J. Wong, R.M. Tuttle, N.Y. Lee, G.W. Randolph, External-beam radiotherapy for differentiated thyroid cancer locoregional control: a statement of the American Head and Neck Society. Head Neck 38, 493–498 (2016)

    Article  PubMed  Google Scholar 

  23. G.W. Randolph, Q.Y. Duh, K.S. Heller, V.A. LiVolsi, S.J. Mandel, D.L. Steward, R.P. Tufano, R.M. Tuttle, 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  PubMed  Google Scholar 

  24. J. Lee, Y. Song, E.Y. Soh, Prognostic significance of the number of metastatic lymph nodes to stratify the risk of recurrence. World J. Surg. 38, 858–862 (2014)

    Article  PubMed  Google Scholar 

  25. R.M. Tuttle, H. Tala, J. Shah, R. Leboeuf, R. Ghossein, M. Gonen, M. Brokhin, G. Omry, J.A. Fagin, A. Shaha, Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system. Thyroid 20, 1341–1349 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. A.L. Ho, M. Dedecjus, L.J. Wirth, R.M. Tuttle, W.B. Inabnet, 3rd, J. Tennvall, F. Vaisman, L. Bastholt, A.G. Gianoukakis, P. Rodien, R. Paschke, R. Elisei, D. Viola, K. So, D. Carroll, T. Hovey, B. Thakre, J.A. Fagin, Selumetinib plus adjuvant radioactive iodine in patients with high-risk differentiated thyroid cancer: a phase III, randomized, placebo-controlled trial (ASTRA). J. Clin. Oncol. 40, Jco2100714 (2022)

Download references

Author information

Authors and Affiliations



T.K. prepared the manuscript and conducted the literature search; T.K. reviewed and edited the manuscript; and T.K., N.S., T.F., M.H., and T.Y. reviewed the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Terufumi Kawamoto.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethical approval

All procedures followed the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent to be included in the study was obtained from all patients. The study protocol was approved by the participating centers’ institutional review boards.

Additional information

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kawamoto, T., Shikama, N., Fukumori, T. et al. Long-term clinical outcomes and prognostic factors for patients with papillary thyroid carcinoma with other organ invasions after adjuvant radioactive iodine. Endocrine 80, 79–85 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: