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CC BY-NC-ND 4.0 · Int Arch Otorhinolaryngol 2021; 25(04): e585-e593
DOI: 10.1055/s-0040-1722253
Original Research

Predictive Factors of Recurrence of Papillary Thyroid Microcarcinomas: Analysis of 2,538 Patients

Andre de Ywata Carvalho 
1   Head and Neck Surgery and Otorhinolaryngology Department, A. C. Camargo Cancer Center, São Paulo, Brazil
,
Hugo Fontan Kohler 
1   Head and Neck Surgery and Otorhinolaryngology Department, A. C. Camargo Cancer Center, São Paulo, Brazil
,
Camila Couto Gomes 
2   Surgical Oncology Division, A. C. Camargo Cancer Center, São Paulo, Brazil
,
José Guilherme Vartanian 
1   Head and Neck Surgery and Otorhinolaryngology Department, A. C. Camargo Cancer Center, São Paulo, Brazil
,
Luiz Paulo Kowalski 
1   Head and Neck Surgery and Otorhinolaryngology Department, A. C. Camargo Cancer Center, São Paulo, Brazil
3   Head and Neck Surgery Department, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
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Abstract

Introduction The incidence of papillary thyroid microcarcinoma (PTMC) has increased, and its treatment remains controversial.

Objective To identify the clinical and pathological factors predictive of tumor recurrence.

Methods We retrospectively analyzed 2,538 consecutive patients treated for PTMC, most submitted to total thyroidectomy (98%) followed by radioactive iodine (RAI) ablation (51.7%) at a cancer center from 1996 to 2015. The patients were stratified according to the American Thyroid Association (ATA) risk categories (low, intermediate, or high), and the clinicopathological features were evaluated by multivariate Cox regression analysis to identify independent prognostic factors for recurrence.

Results After a mean follow-up of 58 months (range: 3 to 236.5 months), tumor recurrence was diagnosed in 63 (2.5%) patients, mostly in the lymph nodes. Distant metastasis occurred in 2 (0.1%) patients. There were no cancer-related deaths. The multivariate analysis showed that age < 55 years (p = 0.049; hazard ratio [HR]: 2.54; 95% confidence interval [95%CI]: 0.95 to 0.99), multifocality (p = 0.032; HR: 1.76; 95%CI: 1.05 to 2.96), and the presence of lymph-node metastasis (p < 0.001; HR: 3.69; 95%CI: 2.07–6.57) were independent risk factors for recurrence. Recurrence was observed in 29 (1.5%) out of 1,940 low-risk patients, 32 (5.4%) out of 590 intermediate-risk patients, and in 2 (25%) out of 8 high-risk patients.

Conclusions The prognosis of PTMC is excellent, favoring a conservative treatment for most patients. Age < 55 years, multifocality, and node metastasis at diagnosis, as well the ATA staging system effectively predict the risk of recurrence. The presence of these risk factors can help identify patients who should be considered for more aggressive management and more frequent follow-up.

Keywords

thyroid - papillary microcarcinoma - recurrence - prognosis - risk stratification


Publication History

Received: 15 June 2020

Accepted: 16 November 2020

Article published online:
19 February 2021

© 2021. Fundação Otorrinolaringologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Wiltshire JJ, Drake TM, Uttley L, Balasubramanian SP. Systematic Review of Trends in the Incidence Rates of Thyroid Cancer. Thyroid 2016; 26 (11) 1541-1552
    CrossrefPubMedGoogle Scholar
  • 2 Roti E, degli Uberti EC, Bondanelli M, Braverman LE. Thyroid papillary microcarcinoma: a descriptive and meta-analysis study. Eur J Endocrinol 2008; 159 (06) 659-673
    CrossrefPubMedGoogle Scholar
  • 3 Londero SC, Krogdahl A, Bastholt L. et al; Danish Thyroid Cancer Group. Papillary thyroid microcarcinoma in Denmark 1996-2008: a national study of epidemiology and clinical significance. Thyroid 2013; 23 (09) 1159-1164
    CrossrefPubMedGoogle Scholar
  • 4 Reinke R, Mathiesen JS, Larsen SR. et al; A study from The Danish Thyroid Cancer Group – DATHYRCA (part of the DAHANCA organization). Incidental and Non-incidental Papillary Thyroid Microcarcinoma in Denmark 1996-2015: A national study on incidence, outcome and thoughts on active surveillance. Cancer Epidemiol 2019; 60: 46-50
    CrossrefPubMedGoogle Scholar
  • 5 Hedinger C, Williams E, Sobin L. 1988. Histologic types of thyroid tumors in World Health Organization histological classification of tumors. 2nd ed.. Verlag: Springer; 9-10
    Google Scholar
  • 6 Zheng W, Wang X, Rui Z, Wang Y, Meng Z, Wang R. Clinical features and therapeutic outcomes of patients with papillary thyroid microcarcinomas and larger tumors. Nucl Med Commun 2019; 40 (05) 477-483
    CrossrefPubMedGoogle Scholar
  • 7 Hay ID, Grant CS, van Heerden JA. et al. Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery 1992; 112: 1139Y1146
    Google Scholar
  • 8 Noguchi S, Yamashita H, Murakami N. et al. Small carcinomas of the thyroid a long-term follow-up of 867 patients. Arch Surg 1996; 131 (02) 187-191
    CrossrefPubMedGoogle Scholar
  • 9 Nabhan F, Ringel MD. Thyroid nodules and cancer management guidelines: comparisons and controversies. Endocr Relat Cancer 2017; 24 (02) R13-R26
    CrossrefPubMedGoogle Scholar
  • 10 Ito Y, Miyauchi A, Oda H. Low-risk papillary microcarcinoma of the thyroid: A review of active surveillance trials. Eur J Surg Oncol 2018; 44 (03) 307-315
    CrossrefPubMedGoogle Scholar
  • 11 Miyauchi A, Ito Y, Oda H. Insights into the Management of Papillary Microcarcinoma of the Thyroid. Thyroid 2018; 28 (01) 23-31
    CrossrefPubMedGoogle Scholar
  • 12 Haugen BR, Alexander EK, Bible KC. 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 2016; 26 (01) 1-133
    CrossrefPubMedGoogle Scholar
  • 13 Shi L, Chen JH, Wang ST, Xiong YQ, Huang T. Treatment for papillary thyroid microcarcinoma. Contemp Oncol (Pozn) 2013; 17 (01) 20-23
    Google Scholar
  • 14 Su H, Li Y. Prophylactic central neck dissection and local recurrence in papillary thyroid microcarcinoma: a meta-analysis. Rev Bras Otorrinolaringol (Engl Ed) 2019; 85 (02) 237-243
    Google Scholar
  • 15 So YK, Seo MY, Son YI. Prophylactic central lymph node dissection for clinically node-negative papillary thyroid microcarcinoma: influence on serum thyroglobulin level, recurrence rate, and postoperative complications. Surgery 2012; 151 (02) 192-198
    CrossrefPubMedGoogle Scholar
  • 16 Ywata de Carvalho A, Chulam TC, Kowalski LP. Long-term Results of Observation vs Prophylactic Selective Level VI Neck Dissection for Papillary Thyroid Carcinoma at a Cancer Center. JAMA Otolaryngol Head Neck Surg 2015; 141 (07) 599-606
    CrossrefPubMedGoogle Scholar
  • 17 Cooper DS, Doherty GM, Haugen BR. et al; American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009; 19 (11) 1167-1214
    CrossrefPubMedGoogle Scholar
  • 18 Kaliszewski K, Zubkiewicz-Kucharska A, Kiełb P, Maksymowicz J, Krawczyk A, Krawiec O. Comparison of the prevalence of incidental and non-incidental papillary thyroid microcarcinoma during 2008-2016: a single-center experience. World J Surg Oncol 2018; 16 (01) 202
    CrossrefPubMedGoogle Scholar
  • 19 Yamamoto Y, Maeda T, Izumi K, Otsuka H. Occult papillary carcinoma of the thyroid. A study of 408 autopsy cases. Cancer 1990; 65 (05) 1173-1179
    CrossrefPubMedGoogle Scholar
  • 20 Harach HR, Franssila KO, Wasenius VM. Occult papillary carcinoma of the thyroid. A “normal” finding in Finland. A systematic autopsy study. Cancer 1985; 56 (03) 531-538
    CrossrefPubMedGoogle Scholar
  • 21 de Matos PS, Ferreira AP, Ward LS. Prevalence of papillary microcarcinoma of the thyroid in Brazilian autopsy and surgical series. Endocr Pathol 2006; 17 (02) 165-173
    CrossrefPubMedGoogle Scholar
  • 22 Mehanna H, Al-Maqbili T, Carter B. et al. Differences in the recurrence and mortality outcomes rates of incidental and nonincidental papillary thyroid microcarcinoma: a systematic review and meta-analysis of 21 329 person-years of follow-up. J Clin Endocrinol Metab 2014; 99 (08) 2834-2843
    CrossrefPubMedGoogle Scholar
  • 23 Karatzas T, Vasileiadis I, Kapetanakis S, Karakostas E, Chrousos G, Kouraklis G. Risk factors contributing to the difference in prognosis for papillary versus micropapillary thyroid carcinoma. Am J Surg 2013; 206 (04) 586-593
    CrossrefPubMedGoogle Scholar
  • 24 Hay ID, Hutchinson ME, Gonzalez-Losada T. et al. Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period. Surgery 2008; 144 (06) 980-987 , discussion 987–988
    CrossrefPubMedGoogle Scholar
  • 25 Ito Y, Miyauchi A, Jikuzono T. et al. Risk factors contributing to a poor prognosis of papillary thyroid carcinoma: validity of UICC/AJCC TNM classification and stage grouping. World J Surg 2007; 31 (04) 838-848
    CrossrefPubMedGoogle Scholar
  • 26 Cappelli C, Castellano M, Braga M. et al. Aggressiveness and outcome of papillary thyroid carcinoma (PTC) versus microcarcinoma (PMC): a mono-institutional experience. J Surg Oncol 2007; 95 (07) 555-560
    CrossrefPubMedGoogle Scholar
  • 27 Giordano D, Gradoni P, Oretti G, Molina E, Ferri T. Treatment and prognostic factors of papillary thyroid microcarcinoma. Clin Otolaryngol 2010; 35 (02) 118-124
    CrossrefPubMedGoogle Scholar
  • 28 Ross DS, Litofsky D, Ain KB. et al. Recurrence after treatment of micropapillary thyroid cancer. Thyroid 2009; 19 (10) 1043-1048
    CrossrefPubMedGoogle Scholar
  • 29 Zheng W, Li J, Lv P, Chen Z, Fan P. Treatment efficacy between total thyroidectomy and lobectomy for patients with papillary thyroid microcarcinoma: A systemic review and meta-analysis. Eur J Surg Oncol 2018; 44 (11) 1679-1684
    CrossrefPubMedGoogle Scholar
  • 30 Hu G, Zhu W, Yang W, Wang H, Shen L, Zhang H. The Effectiveness of Radioactive Iodine Remnant Ablation for Papillary Thyroid Microcarcinoma: A Systematic Review and Meta-analysis. World J Surg 2016; 40 (01) 100-109
    CrossrefPubMedGoogle Scholar
  • 31 Kwon H, Jeon MJ, Kim WG. et al. Lack of Efficacy of Radioiodine Remnant Ablation for Papillary Thyroid Microcarcinoma: Verification Using Inverse Probability of Treatment Weighting. Ann Surg Oncol 2017; 24 (09) 2596-2602
    CrossrefPubMedGoogle Scholar
  • 32 Yang T, Zheng SY, Jiao J, Zou Q, Zhang Y. Radioiodine remnant ablation in papillary thyroid microcarcinoma: a meta-analysis. Nucl Med Commun 2019; 40 (07) 711-719
    CrossrefPubMedGoogle Scholar
  • 33 Mihailovic J, Stefanovic L, Stankovic R. Influence of initial treatment on the survival and recurrence in patients with differentiated thyroid microcarcinoma. Clin Nucl Med 2013; 38 (05) 332-338
    CrossrefPubMedGoogle Scholar
  • 34 Soydal C, Araz M, Ozkan E, Arslantaş E, Kucuk ON, Aras G. Assessment of recurrence rates in papillary thyroid microcarcinoma patients with and without histopathological risk factors after radioiodine ablation treatment. Nucl Med Commun 2015; 36 (02) 109-113
    CrossrefPubMedGoogle Scholar
  • 35 Yi D, Song P, Huang T, Tang X, Sang J. A meta-analysis on the effect of operation modes on the recurrence of papillary thyroid microcarcinoma. Oncotarget 2017; 8 (04) 7148-7156
    CrossrefPubMedGoogle Scholar
  • 36 Gao X, Zhang X, Zhang Y, Hua W, Maimaiti Y, Gao Z. Is papillary thyroid microcarcinoma an indolent tumor?: A retrospective study on 280 cases treated with radioiodine. Medicine (Baltimore) 2016; 95 (40) e5067
    CrossrefPubMedGoogle Scholar
  • 37 Ardito G, Revelli L, Giustozzi E. et al. Aggressive papillary thyroid microcarcinoma: prognostic factors and therapeutic strategy. Clin Nucl Med 2013; 38 (01) 25-28
    CrossrefPubMedGoogle Scholar
  • 38 Qu N, Zhang L, Ji QH. et al. Risk Factors for Central Compartment Lymph Node Metastasis in Papillary Thyroid Microcarcinoma: A Meta-Analysis. World J Surg 2015; 39 (10) 2459-2470
    CrossrefPubMedGoogle Scholar
  • 39 Liu LS, Liang J, Li JH. et al. The incidence and risk factors for central lymph node metastasis in cN0 papillary thyroid microcarcinoma: a meta-analysis. Eur Arch Otorhinolaryngol 2017; 274 (03) 1327-1338
    CrossrefPubMedGoogle Scholar
  • 40 Ruggiero R, Pirozzi R, Gualtieri G. et al. Overview on surgical management of papillary thyroid microcarcinoma. G Chir 2019; 40 (02) 81-87
    PubMedGoogle Scholar
  • 41 Wang X, Lei J, Wei T, Zhu J, Li Z. Clinicopathological characteristics and recurrence risk of papillary thyroid microcarcinoma in the elderly. Cancer Manag Res 2019; 11: 2371-2377
    CrossrefPubMedGoogle Scholar
  • 42 Xu Y, Xu L, Wang J. Clinical predictors of lymph node metastasis and survival rate in papillary thyroid microcarcinoma: analysis of 3607 patients at a single institution. J Surg Res 2018; 221: 128-134
    CrossrefPubMedGoogle Scholar
  • 43 Yu XM, Wan Y, Sippel RS, Chen H. Should all papillary thyroid microcarcinomas be aggressively treated? An analysis of 18,445 cases. Ann Surg 2011; 254 (04) 653-660
    CrossrefPubMedGoogle Scholar
  • 44 Pedrazzini L, Baroli A, Marzoli L, Guglielmi R, Papini E. Cancer recurrence in papillary thyroid microcarcinoma: a multivariate analysis on 231 patients with a 12-year follow-up. Minerva Endocrinol 2013; 38 (03) 269-279
    PubMedGoogle Scholar
  • 45 Siddiqui S, White MG, Antic T. et al. Clinical and Pathologic Predictors of Lymph Node Metastasis and Recurrence in Papillary Thyroid Microcarcinoma. Thyroid 2016; 26 (06) 807-815
    CrossrefPubMedGoogle Scholar
  • 46 Chow SM, Law SC, Chan JK, Au SK, Yau S, Lau WH. Papillary microcarcinoma of the thyroid-Prognostic significance of lymph node metastasis and multifocality. Cancer 2003; 98 (01) 31-40
    CrossrefPubMedGoogle Scholar
  • 47 Mercante G, Frasoldati A, Pedroni C. et al. Prognostic factors affecting neck lymph node recurrence and distant metastasis in papillary microcarcinoma of the thyroid: results of a study in 445 patients. Thyroid 2009; 19 (07) 707-716
    CrossrefPubMedGoogle Scholar
  • 48 Chéreau N, Buffet C, Trésallet C. et al. Does extracapsular extension impact the prognosis of papillary thyroid microcarcinoma?. Ann Surg Oncol 2014; 21 (05) 1659-1664
    CrossrefPubMedGoogle Scholar
  • 49 Baek SK, Jung KY, Kang SM. et al. Clinical risk factors associated with cervical lymph node recurrence in papillary thyroid carcinoma. Thyroid 2010; 20 (02) 147-152
    CrossrefPubMedGoogle Scholar
  • 50 Lee J, Song Y, Soh EY. Central lymph node metastasis is an important prognostic factor in patients with papillary thyroid microcarcinoma. J Korean Med Sci 2014; 29 (01) 48-52
    CrossrefPubMedGoogle Scholar
  • 51 Lombardi CP, Bellantone R, De Crea C. et al. Papillary thyroid microcarcinoma: extrathyroidal extension, lymph node metastases, and risk factors for recurrence in a high prevalence of goiter area. World J Surg 2010; 34 (06) 1214-1221
    CrossrefPubMedGoogle Scholar
  • 52 Ghossein R, Ganly I, Biagini A, Robenshtok E, Rivera M, Tuttle RM. Prognostic factors in papillary microcarcinoma with emphasis on histologic subtyping: a clinicopathologic study of 148 cases. Thyroid 2014; 24 (02) 245-253
    CrossrefPubMedGoogle Scholar
  • 53 Chen Y, Sadow PM, Suh H. et al. BRAF(V600E) Is Correlated with Recurrence of Papillary Thyroid Microcarcinoma: A Systematic Review, Multi-Institutional Primary Data Analysis, and Meta-Analysis. Thyroid 2016; 26 (02) 248-255
    CrossrefPubMedGoogle Scholar
  • 54 Lo CY, Chan WF, Lang BH, Lam KY, Wan KY. Papillary microcarcinoma: is there any difference between clinically overt and occult tumors?. World J Surg 2006; 30 (05) 759-766
    CrossrefPubMedGoogle Scholar
  • 55 Radowsky JS, Howard RS, Burch HB, Stojadinovic A. Impact of degree of extrathyroidal extension of disease on papillary thyroid cancer outcome. Thyroid 2014; 24 (02) 241-244
    CrossrefPubMedGoogle Scholar
  • 56 Jin BJ, Kim MK, Ji YB, Song CM, Park JH, Tae K. Characteristics and significance of minimal and maximal extrathyroidal extension in papillary thyroid carcinoma. Oral Oncol 2015; 51 (08) 759-763
    CrossrefPubMedGoogle Scholar
  • 57 Shin JH, Ha TK, Park HK. et al. Implication of minimal extrathyroidal extension as a prognostic factor in papillary thyroid carcinoma. Int J Surg 2013; 11 (09) 944-947
    CrossrefPubMedGoogle Scholar
  • 58 Qu H, Sun GR, Liu Y, He QS. Clinical risk factors for central lymph node metastasis in papillary thyroid carcinoma: a systematic review and meta-analysis. Clin Endocrinol (Oxf) 2015; 83 (01) 124-132
    CrossrefPubMedGoogle Scholar
  • 59 Vita R, Ieni A, Tuccari G, Benvenga S. The increasing prevalence of chronic lymphocytic thyroiditis in papillary microcarcinoma. Rev Endocr Metab Disord 2018; 19 (04) 301-309
    CrossrefPubMedGoogle Scholar
  • 60 Wang K, Xu J, Li S, Liu S, Zhang L. Population-based study evaluating and predicting the probability of death resulting from thyroid cancer among patients with papillary thyroid microcarcinoma. Cancer Med 2019; 8 (16) 6977-6985
    CrossrefPubMedGoogle Scholar
  • 61 Baudin E, Travagli JP, Ropers J. et al. Microcarcinoma of the thyroid gland: the Gustave-Roussy Institute experience. Cancer 1998; 83 (03) 553-559
    CrossrefPubMedGoogle Scholar
  • 62 Godbert Y, Henriques-Figueiredo B, Cazeau AL. et al. A papillary thyroid microcarcinoma revealed by a single bone lesion with no poor prognostic factors. Case Rep Endocrinol 2013; 2013: 719304
    PubMedGoogle Scholar
  • 63 Tuttle RM, Morris LF, Haughen BR. et al. Thyroid - Differentiated and Anaplastic Carcinoma. In: AJCC Cancer Staging Manual, 8th, Amin MB (Ed). Springer; New York: 2017: 873
    Google Scholar
  • 64 Stefanova DI, Bose A, Ullmann TM. et al. Does the ATA Risk Stratification Apply to Patients with Papillary Thyroid Microcarcinoma?. World J Surg 2020; 44 (02) 452-460
    CrossrefPubMedGoogle Scholar
  • 65 Tuttle RM, Tala H, Shah J. et al. 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 2010; 20 (12) 1341-1349
    CrossrefPubMedGoogle Scholar
  • 66 Verburg FA, Stokkel MP, Düren C. et al. No survival difference after successful (131)I ablation between patients with initially low-risk and high-risk differentiated thyroid cancer. Eur J Nucl Med Mol Imaging 2010; 37 (02) 276-283
    CrossrefPubMedGoogle Scholar