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Multifocality and Progression of Papillary Thyroid Microcarcinoma During Active Surveillance

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Abstract

Background

Prospective trials of active surveillance (AS) have shown low rates of progression in low-risk papillary thyroid microcarcinoma (PTMC; T1aN0M0). However, the significance of multifocality as a prognostic factor remains controversial.

Methods

Data from 571 patients (mean age, 53.1 years; 495 females) who underwent AS were reviewed. PTMC was unifocal in 457 patients (80.0%) and multifocal in 114 patients (20.0%), with 2–5 lesions each (261 tumors in total). Tumor progression was defined as tumor size enlargement ≥ 3 mm and/or development of clinically evident lymph node metastasis (LNM).

Results

After a mean duration of AS of 7.6 years, 53 patients (9.3%) showed tumor enlargement and 8 patients (1.4%) developed LNM. The 10-year progression rate was 13.1%. Age, sex, and calcification pattern did not differ significantly between uni- and multifocal diseases. However, anti-thyroglobulin antibody and/or anti-thyroid peroxidase antibody was more frequently positive with multifocal PTMCs (46.7%) than with unifocal disease (34.4%, p = 0.024). Patients with uni- and multifocal disease showed no significant differences in 10-year rate of tumor enlargement (11.4% vs. 14.8%), LNM development (1.1% vs. 2.4%), or progression (12.4% vs 15.9%). Multivariate analysis of predictors for progression showed multifocality was not a significant risk factor (odds ratio, 1.45; 95% confidence interval, 0.79–2.54; p = 0.22). Eventually, 9 patients (7.9%) with multifocal PTMCs underwent surgery and 7 needed total thyroidectomy, although 7 still showed T1N0M0 low-risk cancer.

Conclusions

Even patients with multiple PTMCs (T1amN0M0) are good candidates for AS. Many patients can avoid total thyroidectomy and subsequent surgical complications.

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References

  1. Davies L, Welch HG (2006) Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA 295:2164–2167

    Article  CAS  PubMed  Google Scholar 

  2. Davies L, Welch HG (2014) Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg 140:317–322

    Article  PubMed  Google Scholar 

  3. Ahn HS, Kim HJ, Welch HG (2014) Korea’s thyroid-cancer “epidemic”–screening and overdiagnosis. N Engl J Med 371:1765–1767

    Article  PubMed  Google Scholar 

  4. Furuya-Kanamori L, Bell KJL, Clark J et al (2016) Prevalence of differentiated thyroid cancer in autopsy studies over six decades: a meta-analysis. J Clin Oncol 34:3672–3679

    Article  PubMed  Google Scholar 

  5. Sugitani I, Toda K, Yamada K et al (2010) Three distinctly different kinds of papillary thyroid microcarcinoma should be recognized: our treatment strategies and outcomes. World J Surg 34:1222–1231

    Article  PubMed  Google Scholar 

  6. Ito Y, Miyauchi A, Kihara M et al (2014) Patient age is significantly related to the progression of papillary microcarcinoma of the thyroid under observation. Thyroid 24:27–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ito Y, Miyauchi A, Kudo T et al (2018) Trends in the implementation of active surveillance for low-risk papillary thyroid microcarcinomas at Kuma Hospital: gradual increase and heterogeneity in the acceptance of this new management option. Thyroid 28:488–495

    Article  PubMed  PubMed Central  Google Scholar 

  8. Sugitani I (2018) Active surveillance for very low-risk papillary thyroid carcinoma: experience and perspectives from Japan. Annals Thyr 3:26–40

    Article  Google Scholar 

  9. Takami H, Ito Y, Okamoto T et al (2011) Therapeutic strategy for differentiated thyroid carcinoma in Japan based on a newly established guideline managed by Japanese society of thyroid surgeons and Japanese association of endocrine surgeons. World J Surg 35:111–121

    Article  PubMed  Google Scholar 

  10. Haugen BR, Alexander EK, Bible KC et al (2016) 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

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sugitani I, Ito Y, Miyauchi A et al (2019) Active surveillance versus immediate surgery: questionnaire survey on the current treatment strategy for adult patients with low-risk papillary thyroid microcarcinoma in Japan. Thyroid 29:1563–1571

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kim HJ, Sohn SY, Jang HW et al (2013) Multifocality, but not bilaterality, is a predictor of disease recurrence/persistence of papillary thyroid carcinoma. World J Surg 37:376–384

    Article  PubMed  Google Scholar 

  13. Zhang W, Jiao D, Liu B et al (2016) Analysis of risk factors contributing to recurrence of papillary thyroid carcinoma in Chinese patients who underwent total thyroidectomy. Med Sci Monit 22:1274–1279

    Article  PubMed  PubMed Central  Google Scholar 

  14. Vasileiadis I, Karakostas E, Charitoudis G et al (2012) Papillary thyroid microcarcinoma: clinicopathological characteristics and implications for treatment in 276 patients. Eur J Clin Invest 42:657–664

    Article  PubMed  Google Scholar 

  15. Qu N, Zhang L, Wu WL et al (2016) Bilaterality weighs more than unilateral multifocality in predicting prognosis in papillary thyroid cancer. Tumour Biol 37:8783–8789

    Article  CAS  PubMed  Google Scholar 

  16. Pyo JS, Sohn JH, Kang G (2016) Detection of tumor multifocality is important for prediction of tumor recurrence in papillary thyroid microcarcinoma: a retrospective study and meta-analysis. J Pathol Transl Med 50:278–286

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sakai T, Sugitani I, Ebina A et al (2019) Active surveillance for T1bN0M0 papillary thyroid carcinoma. Thyroid 29:59–63

    Article  PubMed  Google Scholar 

  18. Fukuoka O, Sugitani I, Ebina A et al (2016) Natural history of asymptomatic papillary thyroid microcarcinoma: time-dependent changes in calcification and vascularity during active surveillance. World J Surg 40:529–537

    Article  PubMed  Google Scholar 

  19. Sugitani I, Ito Y, Takeuchi D et al (2021) Indications and strategy for active surveillance of adult low-risk papillary thyroid microcarcinoma: consensus statements from the japan association of endocrine surgery task force on management for papillary thyroid microcarcinoma. Thyroid 31:183–192

    Article  PubMed  PubMed Central  Google Scholar 

  20. Tuttle RM, Fagin JA, Minkowitz G et al (2017) Natural history and tumor volume kinetics of papillary thyroid cancers during active surveillance. JAMA Otolaryngol Head Neck Surg 143:1015–1020

    Article  PubMed  PubMed Central  Google Scholar 

  21. Shimura H, Haraguchi K, Hiejima Y et al (2005) Distinct diagnostic criteria for ultrasonographic examination of papillary thyroid carcinoma: a multicenter study. Thyroid 15:251–258

    Article  PubMed  Google Scholar 

  22. Koshkina A, Fazelzad R, Sugitani I et al (2020) Association of patient age with progression of low-risk papillary thyroid carcinoma under active surveillance: a systematic review and meta-analysis. JAMA Otolaryngol Head Neck Surg 146:552–560

    Article  PubMed  PubMed Central  Google Scholar 

  23. Sugitani I, Fujimoto Y, Yamada K (2014) Association between serum thyrotropin concentration and growth of asymptomatic papillary thyroid microcarcinoma. World J Surg 38:673–678

    Article  PubMed  Google Scholar 

  24. Kim HI, Jang HW, Ahn HS et al (2018) High serum TSH level is associated with progression of papillary thyroid microcarcinoma during active surveillance. J Clin Endocrinol Metab 103:446–451

    Article  PubMed  Google Scholar 

  25. Miyauchi A, Kudo T, Ito Y et al (2018) Estimation of the lifetime probability of disease progression of papillary microcarcinoma of the thyroid during active surveillance. Surgery 163:48–52

    Article  PubMed  Google Scholar 

  26. Roti E, Degli Uberti EC, Bondanelli M et al (2008) Thyroid papillary microcarcinoma: a descriptive and meta-analysis study. Eur J Endocrinol 159:659–673

    Article  CAS  PubMed  Google Scholar 

  27. Chow SM, Law SC, Chan JK et al (2003) Papillary microcarcinoma of the thyroid-prognostic significance of lymph node metastasis and multifocality. Cancer 98:31–40

    Article  PubMed  Google Scholar 

  28. Kim KJ, Kim SM, Lee YS et al (2015) Prognostic significance of tumor multifocality in papillary thyroid carcinoma and its relationship with primary tumor size: a retrospective study of 2,309 consecutive patients. Ann Surg Oncol 22:125–131

    Article  PubMed  Google Scholar 

  29. Leboulleux S, Rubino C, Baudin E et al (2005) Prognostic factors for persistent or recurrent disease of papillary thyroid carcinoma with neck lymph node metastases and/or tumor extension beyond the thyroid capsule at initial diagnosis. J Clin Endocrinol Metab 90:5723–5729

    Article  CAS  PubMed  Google Scholar 

  30. Neuhold N, Schultheis A, Hermann M et al (2011) Incidental papillary microcarcinoma of the thyroid–further evidence of a very low malignant potential: a retrospective clinicopathological study with up to 30 years of follow-up. Ann Surg Oncol 18:3430–3436

    Article  PubMed  Google Scholar 

  31. Grogan RH, Kaplan SP, Cao H et al (2013) A study of recurrence and death from papillary thyroid cancer with 27 years of median follow-up. Surgery 154:1436–1446

    Article  PubMed  Google Scholar 

  32. Zhu J, Wang X, Zhang X et al (2015) Clinicopathological features of recurrent papillary thyroid cancer. Diagn Pathol 10:96

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Wang F, Yu X, Shen X et al (2017) The prognostic value of tumor multifocality in clinical outcomes of papillary thyroid cancer. J Clin Endocrinol Metab 102:3241–3250

    Article  PubMed  PubMed Central  Google Scholar 

  34. Brito JP, Ito Y, Miyauchi A et al (2016) A clinical framework to facilitate risk stratification when considering an active surveillance alternative to immediate biopsy and surgery in papillary microcarcinoma. Thyroid 26:144–149

    Article  PubMed  PubMed Central  Google Scholar 

  35. Kwon H, Oh HS, Kim M et al (2017) Active surveillance for patients with papillary thyroid microcarcinoma: a single center’s experience in Korea. J Clin Endocrinol Metab 102:1917–1925

    Article  PubMed  Google Scholar 

  36. Sawka AM, Ghai S, Tomlinson G et al (2018) A protocol for a Canadian prospective observational study of decision-making on active surveillance or surgery for low-risk papillary thyroid cancer. BMJ Open 8:e020298

    Article  PubMed  PubMed Central  Google Scholar 

  37. Moon JH, Kim JH, Lee EK et al (2018) Study protocol of multicenter prospective cohort study of active surveillance on papillary thyroid microcarcinoma (MAeSTro). Endocrinol Metab Seoul 33:278–286

    Article  PubMed  PubMed Central  Google Scholar 

  38. Mao J, Zhang Q, Zhang H et al (2020) Risk factors for lymph node metastasis in papillary thyroid carcinoma: a systematic review and meta-analysis. Front Endocrinol Lausanne 11:265

    Article  PubMed  PubMed Central  Google Scholar 

  39. Molnár C, Molnár S, Bedekovics J et al (2019) Thyroid carcinoma coexisting with Hashimoto’s thyreoiditis: clinicopathological and molecular characteristics clue up pathogenesis. Pathol Oncol Res 25:1191–1197

    Article  PubMed  CAS  Google Scholar 

  40. Liang J, Zeng W, Fang F et al (2017) Clinical analysis of Hashimoto thyroiditis coexistent with papillary thyroid cancer in 1392 patients. Acta Otorhinolaryngol Ital 37:393–400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhu F, Shen YB, Li FQ et al (2016) The effects of hashimoto thyroiditis on lymph node metastases in unifocal and multifocal papillary thyroid carcinoma: a retrospective Chinese cohort study. Med Baltimore 95:e2674

    Article  CAS  Google Scholar 

  42. Marotta V, Sciammarella C, Chiofalo MG et al (2017) Hashimoto’s thyroiditis predicts outcome in intrathyroidal papillary thyroid cancer. Endocr Relat Cancer 24:485–493

    Article  CAS  PubMed  Google Scholar 

  43. Lee JH, Kim Y, Choi JW et al (2013) The association between papillary thyroid carcinoma and histologically proven Hashimoto’s thyroiditis: a meta-analysis. Eur J Endocrinol 168:343–349

    Article  CAS  PubMed  Google Scholar 

  44. Konturek A, Barczyński M, Nowak W et al (2014) Risk of lymph node metastases in multifocal papillary thyroid cancer associated with Hashimoto’s thyroiditis. Langenbecks Arch Surg 399:229–236

    Article  PubMed  PubMed Central  Google Scholar 

  45. Brito JP, Gionfriddo MR, Al Nofal A et al (2014) The accuracy of thyroid nodule ultrasound to predict thyroid cancer: systematic review and meta-analysis. J Clin Endocrinol Metab 99:1253–1263

    Article  CAS  PubMed  Google Scholar 

  46. Campanella P, Ianni F, Rota CA et al (2014) Quantification of cancer risk of each clinical and ultrasonographic suspicious feature of thyroid nodules: a systematic review and meta-analysis. Eur J Endocrinol 170:R203-211

    Article  CAS  PubMed  Google Scholar 

  47. Remonti LR, Kramer CK, Leitão CB et al (2015) Thyroid ultrasound features and risk of carcinoma: a systematic review and meta-analysis of observational studies. Thyroid 25:538–550

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We wish to acknowledge and thank Dr. Toshiaki Otsuka, Department of Hygiene and Public Health, Nippon Medical School, Tokyo, Japan, for assistance with statistical analysis. This work was partially supported by JSPS KAKENHI Grant Number 20K08995.

Funding

This work was partially supported by JSPS KAKENHI Grant Number 20K08995.

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Authors and Affiliations

  1. Department of Endocrine Surgery, Nippon Medical School Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan

    Ryuta Nagaoka, Aya Ebina, Tomoo Jikuzono, Marie Saitou, Masaomi Sen, Hiroko Kazusaka, Mami Matsui & Iwao Sugitani

  2. Division of Head and Neck, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Aya Ebina, Kazuhisa Toda, Hiroki Mitani & Iwao Sugitani

  3. Division of Ultrasonography, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Keiko Yamada

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  1. Ryuta Nagaoka
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Contributions

RN and IS contributed to study concept, design, statistical data analysis, interpretation and writing; RN, AE, KT, TJ, MS, MS, HK, MM, KY, HM and IS carried out acquisition of the data; KY, HM and IS performed validation; IS performed supervision, project administration and fund acquisition. All authors contributed to drafting of the manuscript and critical revisions and agreed to publication of the submitted version of the manuscript.

Corresponding author

Correspondence to Ryuta Nagaoka.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The protocol for this prospective trial was approved by the ethics committee of Cancer Institute Hospital in 1994.

Consent participation

Written consent for participation was obtained after agreement based on the informed decision of the patient. The institutional review board of Nippon Medical School also approved this retrospective study using the prospectively collected database in 2019.

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Nagaoka, R., Ebina, A., Toda, K. et al. Multifocality and Progression of Papillary Thyroid Microcarcinoma During Active Surveillance. World J Surg 45, 2769–2776 (2021). https://doi.org/10.1007/s00268-021-06185-2

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