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Undercover active surveillance of small highly suspicious thyroid nodules without fine needle aspiration

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Abstract

Purpose

Active surveillance (AS) is an alternative treatment approach for small, low-risk papillary thyroid microcarcinoma (PTMC). This study aimed to assess the clinical outcomes of small, highly suspicious nodules lacking initial cytological confirmation.

Methods

This study included 112 patients with highly suspicious nodules measuring ≤ 10 mm who underwent serial ultrasound at Asan Medical Center, Korea, between 2010 and 2023.

Results

The median participant age was 51.9 years, and 74.1% were female. The median maximal tumor diameter and tumor volume (TV) were 4.5 (interquartile range [IQR] 3.7–5.2, range 2.2–9.3) mm and 25.2 (IQR 13.1–49.2) mm3, respectively. During a median follow-up period of 4.8 years, four (3.6%) patients showed a ≥ 3 mm increase in maximal diameter, and two (1.8%) developed new lymph node (LN) metastasis. Disease progression was associated with a TV doubling time (TVDT) of < 5 years and a ≥ 75% increase in TV (p = 0.017 and p < 0.005, respectively). Furthermore, 34.8% of patients underwent fine needle aspiration (FNA), primarily at their own request, yielding 46.2%, 5.1%, 41.0%, and 12.8 % malignant, benign, indeterminate, and non-diagnostic results, respectively. Of 18 patients with PTMC, 8 (44.4%) underwent surgery and 10 continued AS, with no LN metastasis during AS and no postoperative recurrence.

Conclusion

Small, highly suspicious nodules had a low disease progression rate during AS without FNA. Disease progression was associated with a TVDT of < 5 years and a ≥ 75% increase in TV. FNA can be performed more conservatively than it currently is in patients with highly suspicious nodules measuring ≤ 10 mm.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. M. Pizzato, M. Li, J. Vignat, M. Laversanne, D. Singh, C. La Vecchia, S. Vaccarella, The epidemiological landscape of thyroid cancer worldwide: GLOBOCAN estimates for incidence and mortality rates in 2020. Lancet Diab. Endocrinol. 10(4), 264–272 (2022). https://doi.org/10.1016/s2213-8587(22)00035-3

    Article  Google Scholar 

  2. H. Sung, J. Ferlay, R.L. Siegel, M. Laversanne, I. Soerjomataram, A. Jemal, F. Bray, Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 71(3), 209–249 (2021). https://doi.org/10.3322/caac.21660

    Article  PubMed  Google Scholar 

  3. H.S. Ahn, H.J. Kim, H.G. Welch, Korea’s thyroid-cancer “epidemic”: screening and overdiagnosis. N. Engl. J. Med. 371(19), 1765–1767 (2014). https://doi.org/10.1056/NEJMp1409841

    Article  PubMed  Google Scholar 

  4. A. Miyauchi, Y. Ito, M. Fujishima, A. Miya, N. Onoda, M. Kihara, T. Higashiyama, H. Masuoka, S. Kawano, T. Sasaki, M. Nishikawa, S. Fukata, T. Akamizu, M. Ito, E. Nishihara, M. Hisakado, K. Kosaka, M. Hirokawa, T. Hayashi, Long-Term Outcomes of Active Surveillance and Immediate Surgery for Adult Patients with Low-Risk Papillary Thyroid Microcarcinoma: 30-Year Experience. Thyroid 33(7), 817–825 (2023). https://doi.org/10.1089/thy.2023.0076

    Article  PubMed  PubMed Central  Google Scholar 

  5. S.J. Cho, C.H. Suh, J.H. Baek, S.R. Chung, Y.J. Choi, K.W. Chung, Y.K. Shong, J.H. Lee, Active Surveillance for Small Papillary Thyroid Cancer: A Systematic Review and Meta-Analysis. Thyroid 29(10), 1399–1408 (2019). https://doi.org/10.1089/thy.2019.0159

    Article  PubMed  Google Scholar 

  6. R. Chou, T. Dana, M. Haymart, A.M. Leung, R.P. Tufano, J.A. Sosa, M.D. Ringel, Active Surveillance Versus Thyroid Surgery for Differentiated Thyroid Cancer: A Systematic Review. Thyroid 32(4), 351–367 (2022). https://doi.org/10.1089/thy.2021.0539

    Article  CAS  PubMed  Google Scholar 

  7. H.S. Oh, J. Ha, H.I. Kim, T.H. Kim, W.G. Kim, D.J. Lim, T.Y. Kim, S.W. Kim, W.B. Kim, Y.K. Shong, J.H. Chung, J.H. Baek, Active Surveillance of Low-Risk Papillary Thyroid Microcarcinoma: A Multi-Center Cohort Study in Korea. Thyroid 28(12), 1587–1594 (2018). https://doi.org/10.1089/thy.2018.0263

    Article  PubMed  Google Scholar 

  8. 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), 1–133 (2016). https://doi.org/10.1089/thy.2015.0020

    Article  PubMed  PubMed Central  Google Scholar 

  9. R.M. Tuttle, J.A. Fagin, G. Minkowitz, R.J. Wong, B. Roman, S. Patel, B. Untch, I. Ganly, A.R. Shaha, J.P. Shah, M. Pace, D. Li, A. Bach, O. Lin, A. Whiting, R. Ghossein, I. Landa, M. Sabra, L. Boucai, S. Fish, L.G.T. Morris, Natural History and Tumor Volume Kinetics of Papillary Thyroid Cancers During Active Surveillance. JAMA Otolaryngol. Head Neck Surg. 143(10), 1015–1020 (2017). https://doi.org/10.1001/jamaoto.2017.1442

    Article  PubMed  PubMed Central  Google Scholar 

  10. A.S. Ho, S. Kim, C. Zalt, M.L. Melany, I.E. Chen, J. Vasquez, J. Mallen-St Clair, M.M. Chen, M. Vasquez, X. Fan, W.K. van Deen, R.W. Haile, T.J. Daskivich, Z.S. Zumsteg, G.D. Braunstein, W.L. Sacks, Expanded Parameters in Active Surveillance for Low-risk Papillary Thyroid Carcinoma: A Nonrandomized Controlled Trial. JAMA Oncol. 8(11), 1588–1596 (2022). https://doi.org/10.1001/jamaoncol.2022.3875

    Article  PubMed  PubMed Central  Google Scholar 

  11. T. Sakai, I. Sugitani, A. Ebina, O. Fukuoka, K. Toda, H. Mitani, K. Yamada, Active Surveillance for T1bN0M0 Papillary Thyroid Carcinoma. Thyroid 29(1), 59–63 (2019). https://doi.org/10.1089/thy.2018.0462

    Article  PubMed  Google Scholar 

  12. G. Russ, S.J. Bonnema, M.F. Erdogan, C. Durante, R. Ngu, L. Leenhardt, European Thyroid Association Guidelines for Ultrasound Malignancy Risk Stratification of Thyroid Nodules in Adults: The EU-TIRADS. Eur. Thyroid J. 6(5), 225–237 (2017). https://doi.org/10.1159/000478927

    Article  PubMed  PubMed Central  Google Scholar 

  13. E.J. Ha, S.R. Chung, D.G. Na, H.S. Ahn, J. Chung, J.Y. Lee, J.S. Park, R.E. Yoo, J.H. Baek, S.M. Baek, S.W. Cho, Y.J. Choi, S.Y. Hahn, S.L. Jung, J.H. Kim, S.K. Kim, S.J. Kim, C.Y. Lee, H.K. Lee, J.H. Lee, Y.H. Lee, H.K. Lim, J.H. Shin, J.S. Sim, J.Y. Sung, J.H. Yoon, M. Choi, 2021 Korean Thyroid Imaging Reporting and Data System and Imaging-Based Management of Thyroid Nodules: Korean Society of Thyroid Radiology Consensus Statement and Recommendations. Korean J. Radiol. 22(12), 2094–2123 (2021). https://doi.org/10.3348/kjr.2021.0713

    Article  PubMed  PubMed Central  Google Scholar 

  14. S.M. Ha, J.K. Kim, J.H. Baek, Detection of Malignancy Among Suspicious Thyroid Nodules <1 cm on Ultrasound with Various Thyroid Image Reporting and Data Systems. Thyroid 27(10), 1307–1315 (2017). https://doi.org/10.1089/thy.2017.0034

    Article  CAS  PubMed  Google Scholar 

  15. P.W. Rosario, A.L. Silva, M.R. Calsolari, Is fine needle aspiration really not necessary in patients with thyroid nodules ≤ 1 cm with highly suspicious features on ultrasonography and candidates for active surveillance? Diagn. Cytopathol. 45(4), 294–296 (2017). https://doi.org/10.1002/dc.23673

    Article  PubMed  Google Scholar 

  16. H.J. Moon, E. Son, E.K. Kim, J.H. Yoon, J.Y. Kwak, The diagnostic values of ultrasound and ultrasound-guided fine needle aspiration in subcentimeter-sized thyroid nodules. Ann. Surg. Oncol. 19(1), 52–59 (2012). https://doi.org/10.1245/s10434-011-1813-1

    Article  PubMed  Google Scholar 

  17. J.Y. Kwak, E.K. Kim, M.J. Kim, E.J. Son, Significance of sonographic characterization for managing subcentimeter thyroid nodules. Acta. Radiol. 50(8), 917–923 (2009). https://doi.org/10.1080/02841850903062724

    Article  PubMed  Google Scholar 

  18. D. Berker, Y. Aydin, I. Ustun, K. Gul, Y. Tutuncu, S. Işik, T. Delibasi, S. Guler, The value of fine-needle aspiration biopsy in subcentimeter thyroid nodules. Thyroid 18(6), 603–608 (2008). https://doi.org/10.1089/thy.2007.0313

    Article  PubMed  Google Scholar 

  19. K.L. Partyka, H.H. Wu, Fine-needle aspirates of thyroid microcarcinoma. J. Am. Soc. Cytopathol. 6(6), 236–241 (2017). https://doi.org/10.1016/j.jasc.2017.06.006

    Article  PubMed  Google Scholar 

  20. A. Rozenbaum, C. Buffet, C. Bigorgne, B. Royer, A. Rouxel, M. Bienvenu, N. Chereau, F. Menegaux, L. Leenhardt, G. Russ, Outcomes of active surveillance of EU-TIRADS 5 thyroid nodules. Eur. J. Endocrinol. 184(5), 677–686 (2021). https://doi.org/10.1530/eje-20-1481

    Article  CAS  PubMed  Google Scholar 

  21. S.R. Chung, Y.J. Choi, S.S. Lee, S.O. Kim, S.A. Lee, M.J. Jeon, W.G. Kim, J.H. Lee, J.H. Baek, Interobserver Reproducibility in Sonographic Measurement of Diameter and Volume of Papillary Thyroid Microcarcinoma. Thyroid 31(3), 452–458 (2021). https://doi.org/10.1089/thy.2020.0317

    Article  CAS  PubMed  Google Scholar 

  22. W.K. Jeong, J.H. Baek, H. Rhim, Y.S. Kim, M.S. Kwak, H.J. Jeong, D. Lee, Radiofrequency ablation of benign thyroid nodules: safety and imaging follow-up in 236 patients. Eur. Radiol. 18(6), 1244–1250 (2008). https://doi.org/10.1007/s00330-008-0880-6

    Article  PubMed  Google Scholar 

  23. Kuma Hospital, Doubling time and progression calculator. www.kuma-h.or.jp/english/about/doubling-time-progression calculator (2019). Accessed 4 August 2023

  24. O. Fukuoka, I. Sugitani, A. Ebina, K. Toda, K. Kawabata, K. Yamada, Natural History of Asymptomatic Papillary Thyroid Microcarcinoma: Time-Dependent Changes in Calcification and Vascularity During Active Surveillance. World J. Surg. 40(3), 529–537 (2016). https://doi.org/10.1007/s00268-015-3349-1

    Article  PubMed  Google Scholar 

  25. H. Kwon, H.S. Oh, M. Kim, S. Park, M.J. Jeon, W.G. Kim, W.B. Kim, Y.K. Shong, D.E. Song, J.H. Baek, K.W. Chung, T.Y. Kim, Active Surveillance for Patients With Papillary Thyroid Microcarcinoma: A Single Center’s Experience in Korea. J. Clin. Endocrinol. Metab. 102(6), 1917–1925 (2017). https://doi.org/10.1210/jc.2016-4026

    Article  PubMed  Google Scholar 

  26. M.J. Jeon, W.G. Kim, K.W. Chung, J.H. Baek, W.B. Kim, Y.K. Shong, Active Surveillance of Papillary Thyroid Microcarcinoma: Where Do We Stand? Eur. Thyroid J. 8(6), 298–306 (2019). https://doi.org/10.1159/000503064

    Article  PubMed  PubMed Central  Google Scholar 

  27. A. Miyauchi, T. Kudo, Y. Ito, H. Oda, M. Yamamoto, H. Sasai, T. Higashiyama, H. Masuoka, M. Fukushima, M. Kihara, A. Miya, Natural history of papillary thyroid microcarcinoma: Kinetic analyses on tumor volume during active surveillance and before presentation. Surgery 165(1), 25–30 (2019). https://doi.org/10.1016/j.surg.2018.07.045

    Article  PubMed  Google Scholar 

  28. H.S. Oh, H. Kwon, E. Song, M.J. Jeon, T.Y. Kim, J.H. Lee, W.B. Kim, Y.K. Shong, K.W. Chung, J.H. Baek, W.G. Kim, Tumor Volume Doubling Time in Active Surveillance of Papillary Thyroid Carcinoma. Thyroid 29(5), 642–649 (2019). https://doi.org/10.1089/thy.2018.0609

    Article  PubMed  Google Scholar 

  29. M. Jin, H.I. Kim, J. Ha, M.J. Jeon, W.G. Kim, D.J. Lim, T.Y. Kim, J.H. Chung, Y.K. Shong, T.H. Kim, W.B. Kim, Tumor Volume Doubling Time in Active Surveillance of Papillary Thyroid Microcarcinoma: A Multicenter Cohort Study in Korea. Thyroid 31(10), 1494–1501 (2021). https://doi.org/10.1089/thy.2021.0094

    Article  CAS  PubMed  Google Scholar 

  30. Y. Ito, A. Miyauchi, T. Kudo, T. Higashiyama, H. Masuoka, M. Kihara, A. Miya, Kinetic analysis of growth activity in enlarging papillary thyroid microcarcinomas. Thyroid 29(12), 1765–1773 (2019). https://doi.org/10.1089/thy.2019.0396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Y. Ito, A. Miyauchi, M. Kihara, T. Higashiyama, K. Kobayashi, A. Miya, Patient age is significantly related to the progression of papillary microcarcinoma of the thyroid under observation. Thyroid 24(1), 27–34 (2014). https://doi.org/10.1089/thy.2013.0367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. R.M. Tuttle, J. Fagin, G. Minkowitz, R. Wong, B. Roman, S. Patel, B. Untch, I. Ganly, A. Shaha, J. Shah, D. Li, A. Bach, J. Girshman, O. Lin, M. Cohen, J.M. Cohen, J. Cracchiolo, R. Ghossein, M. Sabra, L. Boucai, S. Fish, L. Morris, Active Surveillance of Papillary Thyroid Cancer: Frequency and Time Course of the Six Most Common Tumor Volume Kinetic Patterns. Thyroid 32(11), 1337–1345 (2022). https://doi.org/10.1089/thy.2022.0325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Y. Ito, A. Miyauchi, H. Inoue, M. Fukushima, M. Kihara, T. Higashiyama, C. Tomoda, Y. Takamura, K. Kobayashi, A. Miya, An observational trial for papillary thyroid microcarcinoma in Japanese patients. World J. Surg. 34(1), 28–35 (2010). https://doi.org/10.1007/s00268-009-0303-0

    Article  PubMed  Google Scholar 

  34. C.M. Oh, K.W. Jung, Y.J. Won, A. Shin, H.J. Kong, J.S. Lee, Age-Period-Cohort Analysis of Thyroid Cancer Incidence in Korea. Cancer Res. Treat. 47(3), 362–369 (2015). https://doi.org/10.4143/crt.2014.110

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

A part of this study was presented as an abstract at a meeting of the Seoul International Congress of Endocrinology and Metabolism in 2023. This study work was supported by a grant (Grant number 2023IL0010) from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.

Author contributions

C.A.K., Y.K.S., and W.G.K. contributed to the study conceptualization and design. C.A.K., J.Y., and H.-S.O. performed data collection. C.A.K. and M.J.J. conducted the statistical analysis and visualization of the results. C.A.K., S.R.C., J.H.B., W.B.K., and W.G.K. contributed to the interpretation of data and manuscript editing. The first draft of the manuscript was written by C.A.K.; Y.K.S. and W.G.K. reviewed and edited the manuscript. All the authors had full access to the data, take responsibility for the accuracy of the data analysis, and approved the final version of the manuscript.

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Authors and Affiliations

  1. Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Chae A Kim, Jungmin Yoo, Hye-Seon Oh, Min Ji Jeon, Won Bae Kim, Young Kee Shong & Won Gu Kim

  2. Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Sae Rom Chung & Jung Hwan Baek

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  1. Chae A Kim
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Correspondence to Won Gu Kim.

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This study was performed in line with the principles of the Declaration of Helsinki. The study protocol was approved by the Institutional Review Board of Asan Medical Center, Seoul, Republic of Korea.

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Kim, C.A., Yoo, J., Oh, HS. et al. Undercover active surveillance of small highly suspicious thyroid nodules without fine needle aspiration. Endocrine (2023). https://doi.org/10.1007/s12020-023-03601-6

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