, Volume 63, Issue 1, pp 79–86 | Cite as

Clinical and prognostic role of detection timing of distant metastases in patients with differentiated thyroid cancer

  • Domenico AlbanoEmail author
  • Maria Beatrice Panarotto
  • Rexhep Durmo
  • Carlo Rodella
  • Francesco Bertagna
  • Raffaele Giubbini
Original Article



Distant metastases (DM) from DTC occur in 5–25% of cases and are correlated to lower survival; the prognostic significance of the temporal onset of DM is unclear. Our aim was to retrospectively analyze the prevalence of DM and to assess the prognostic role of the timing of manifestation of DM regarding the outcome.

Materials and methods

We included 174 patients (mean age 64 years). According to the time of manifestation, DM were divided in two groups: synchronous DM (SDM, n = 108) defined as metastases present at initial diagnosis and metachronous DM (MDM, n = 66) as diagnosed during follow-up. SDM were further sub grouped in pre-RAIT when diagnosed during pre-surgery work-up (n = 35) and baseline-RAIT when detected by first whole body scan after RAIT (n = 73). Disease-specific survival (DSS) was analyzed using the Kaplan–Meier method.


Total RAI activities and number of treatments were significantly higher in MDM, also loss of RAI avidity was more frequent in MDM. Forty-four patients died during follow-up, of which 41 were DTC-related deaths, 5-year and 10-year DSS were 80% and 56%. On univariate analysis MDM had significantly shorter DSS; also histotype and RAI avidity were significant risk factors of impaired survival. On multivariate analysis, only loss of RAI avidity remained as independent negative predictor (p = 0.043). Considering SDM, DSS was significantly shorter in pre-RAIT group than baseline-RAIT (p = 0.004). Instead there was no significant difference between pre-RAIT-SDM and MDM in survival outcome (p = 0.875).


In DTC with DM, loss of RAI uptake has an important role in survival. No significant difference in survival outcome was discovered between SDM and MDM; but, among SDM, pre-RAIT had significant shorter DSS than baseline-RAIT.


RAI Differentiated thyroid cancer Prognosis Distant metastases 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participant included in the study


  1. 1.
    S.I. Sherman, Thyroid carcinoma. Lancet 361, 501–511 (2003)CrossRefGoogle Scholar
  2. 2.
    B.R. Haugen, E.K. Alexander, K.C. Bible, G.M. Doherty, S.J. Mandel, Y.E. Nikiforov 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 26, 1–133 (2016)CrossRefGoogle Scholar
  3. 3.
    E.P. Simard, E.M. Ward, R. Siegel, A. Jemal, Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J. Clin. 62, 118–128 (2012)CrossRefGoogle Scholar
  4. 4.
    E. Sampson, J.D. Brierley, L.W. Le, L. Rotstein, R.W. Tsang, Clinical management and outcome of papillary and follicular (differentiated) thyroid cancer presenting with distant metastasis at diagnosis. Cancer 110, 1451–1456 (2007)CrossRefGoogle Scholar
  5. 5.
    M. Schlumberger, M. Tubiana, F. De Vathaire, C. Hill, P. Gardet, J.P. Travagli et al. Long term results of treatment of 283 patients with lung and bone metastases from differentiated thyroid carcinoma. J. Clin. Endocrinol. Metab. 63, 960–967 (1986)CrossRefGoogle Scholar
  6. 6.
    D. Albano, F. Bertagna, M. Bertoli, M. Bonacina, R. Durmo, E. Cerudelli et al. Possible delayed diagnosis and treatment of metastatic differentiated thyroid cancer by adopting the 2015 ATA guidelines. Eur. J. Endo. (2018)
  7. 7.
    M. Haq, C. Harmer, Differentiated thyroid carcinoma with distant metastases at presentation: prognostic factors and outcome. Clin. Endocrinol. 63, 87–93 (2005)CrossRefGoogle Scholar
  8. 8.
    F.A. Verburg, M. Luster, Radioactive iodine (RAI) therapy for metastatic differentiated thyroid cancer. Best. Pract. Res Clin. Endocrinol. Metab. 31, 279–290 (2017)CrossRefGoogle Scholar
  9. 9.
    M. Shoup, A. Stojadinovic, A. Nissan, R.A. Ghossein, S. Freedman, M.F. Brennan et al. Prognostic indicators of outcomes in patients with distantmetastasesfromdifferentiated thyroid carcinoma. J. Am. Coll. Surg. 197, 191–197 (2003)CrossRefGoogle Scholar
  10. 10.
    A. Stojadinovic, M. Shoup, R.A. Ghossein, A. Nissan, M.F. Brennan, J.P. Shah et al. The role of operations for distantly metastatic well-differentiated thyroid carcinoma. Surgery 131, 636–643 (2002)CrossRefGoogle Scholar
  11. 11.
    J.M. Mihailovic, L.J. Stefanovic, M.D. Malesevic, M.D. Erak, D.D. Tesanovic, Metastatic differentiated thyroid carcinoma: clinical management and outcome of disease in patients with initial and late distant metastases. Nucl. Med. Commun. 30, 558–564 (2009)CrossRefGoogle Scholar
  12. 12.
    Y. Orita, I. Sugitani, M. Matsuura, M. Ushijima, K. Tsukahara, Y. Fujimoto et al. Prognostic factors and the therapeutic strategy for patients with bone metastasis from differentiated thyroid carcinoma. Surgery 147, 424–431 (2010)CrossRefGoogle Scholar
  13. 13.
    F. Pitoia, F. Bueno, G. Cross, Long-term survival and low-effective cumulative radioiodine doses to achieve remission in patients with 131iodine-avid lung metastasis from differentiated thyroid cancer. Clin. Nucl. Med. 39, 784–790 (2014)CrossRefGoogle Scholar
  14. 14.
    A. Sabet, I. Binse, S. Dogan, A. Koch, S.J. Rosenbaum-Krumme, H.J. Biersack et al. Distinguishing sinchronous from metachronous manifestation of distant metastases: a prognostic feature in differentiated thyroid carcinoma. Eur. J. Nucl. Med. Mol. Imaging 44, 190–195 (2017)CrossRefGoogle Scholar
  15. 15.
    M. Luster, S.E. Clarke, M. Dietlein, M. Lassmann, P. Lind, W.J. Oyen et al. European Association of Nuclear Medicine (EANM). Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur. J. Nucl. Med. Mol. Imaging 35, 1941–1959 (2008)CrossRefGoogle Scholar
  16. 16.
    S.B. Edge, D.R. Byrd, C.C. Compton, A. G. Fritz, F. L. Greene, A. Trotti (eds.) AJCC Cancer Staging Manual. 7th edn. (Springer, New York, 2010).Google Scholar
  17. 17.
    J. Lee, E.Y. Soh, Differentiated thyroid carcinoma presenting with distant metastasis at initial diagnosis clinical outcomes and prognostic factors. Ann. Surg. 251, 114–119 (2010)CrossRefGoogle Scholar
  18. 18.
    B.H. Lang, K.P. Wong, C.Y. Cheung, K.Y. Wan, C.Y. Lo, Evaluating the prognostic factors associated with cancer-specific survival of differentiated thyroid carcinoma presenting with distant metastasis. Ann. Surg. Oncol. 20, 1329–1335 (2013)CrossRefGoogle Scholar
  19. 19.
    I.J. Nixon, M.M. Whitcher, F.L. Palmer, R.M. Tuttle, A.R. Shaha, J.P. Shah et al. The impact of distant metastases at presentation on prognosis in patients with differentiated carcinoma of the thyroid gland. Thyroid 22, 884–889 (2012)CrossRefGoogle Scholar
  20. 20.
    S.F. Dinneen, M.J. Valimaki, E.J. Bergstralh, J.R. Goellner, C.A. Gorman, I.D. Hay, Distant metastases in papillary thyroidcarcinoma:100 cases observed at one institution during 5 decades. J. Clin. Endocrinol. Metab. 80, 2041–2045 (1995)Google Scholar
  21. 21.
    C. Durante, N. Haddy, E. Baudin, S. Leboulleux, D. Hartl, J.P. Travagli et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J. Clin. Endocrinol. Metab. 91, 2892–2899 (2006)CrossRefGoogle Scholar
  22. 22.
    U. Feine, R. Lietzenmayer, J.P. Hanke, H. Wöhrle, W. Müller-Schauenburg, 18FDG whole body PET in differentiated thyroid carcinoma. Flipflop in uptake patterns of 18FDG and 131I. Nuklearmedizin 34, 127–134 (1995)CrossRefGoogle Scholar
  23. 23.
    F. Bertagna, D. Albano, G. Bosio, A. Piccardo, B. Dib, R. Giubbini, 18F-FDG-PET/CT in patients affected by differentiated thyroid carcinoma with positive thyroglobulin level and negative 131I whole body scan. it’s value confirmed by a bicentric experience. Curr. Radiopharm. 9, 228–234 (2016)CrossRefGoogle Scholar
  24. 24.
    C.I. Lundgren, P. Hall, P.W. Dickman, J. Zedenius, Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case–control study. Cancer 106, 524–531 (2006)CrossRefGoogle Scholar
  25. 25.
    I.D. Hay, E.J. Bergstralh, J.R. Goellner, J.R. Ebersold, C.S. Grant, Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989. Surgery 114, 1050–1057 (1993)Google Scholar
  26. 26.
    M.Y. Do, Y. Rhee, D.J. Kim, C.S. Kim, K.H. Nam, C.W. Ahn et al. Clinical features of bone metastases resulting from thyroid cancer: a review of 28 patients over a 20-year period. Endocr. J. 52, 701–707 (2005)CrossRefGoogle Scholar
  27. 27.
    S.W. Cho, H.S. Choi, G.J. Yeom, J.A. Lim, J.H. Moon, D.J. Park et al. Long-term prognosis of differentiated thyroid cancer with lung metastasis in Korea and its prognostic factors. Thyroid 24, 277–286 (2014)CrossRefGoogle Scholar
  28. 28.
    G. Riesco-Eizaguirre, P. Gutierrez-Martinez, M.A. Garcia-Cabezas, M. Nistal, P. Santisteban, The oncogene BRAF V600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na + /I- targeting to the membrane. Endocr. Relat. Cancer 13, 257–269 (2006)CrossRefGoogle Scholar
  29. 29.
    Y.M. Choi, W.G. Kim, H. Kwoon, M.J. Jeon, J.J. Lee, J.S. Ryu et al. Early prognostic factors at the time of diagnosis of bone metastasis in patients with bone metastases of differentiated thyroid carcinoma. Eur. J. End. 175, 165–172 (2016)CrossRefGoogle Scholar
  30. 30.
    E. Hindie, P. Zanotti-Fregonara, I. Keller, F. Duron, J.Y. Devaux, M. Calzada-Nocaudie et al. Bone metastases of differentiated thyroid cancer: impact of early 131I-based detection on outcome. Endocr. Relat. Cancer 14, 799–807 (2007)CrossRefGoogle Scholar
  31. 31.
    E. Robenshtok, A. Farooki, R.K. Grewal, R.M. Tuttle, Natural history of small radioiodine-avid bone metastases that have no structural correlate on imaging studies. Endocrine 47, 266–272 (2014)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Domenico Albano
    • 1
    Email author
  • Maria Beatrice Panarotto
    • 1
  • Rexhep Durmo
    • 1
  • Carlo Rodella
    • 2
  • Francesco Bertagna
    • 3
  • Raffaele Giubbini
    • 3
  1. 1.Nuclear MedicineSpedali Civili BresciaBresciaItaly
  2. 2.Health Physics DepartmentSpedali CiviliBresciaItaly
  3. 3.Nuclear MedicineUniversity of Brescia and Spedali Civili BresciaBresciaItaly

Personalised recommendations