Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
2012; Elsevier BV; Volume: 23; Linguagem: Inglês
10.1093/annonc/mds230
ISSN1569-8041
AutoresFurio Pacini, Maria Grazia Castagna, Lucia Brilli, George Pentheroudakis,
Tópico(s)Thyroid and Parathyroid Surgery
ResumoThyroid cancer is the most common of the endocrine malignancies and it represents <1% of all human tumors. The annual incidence of thyroid cancer varies considerably by geographic area, age and sex. A recent review reported an overall incidence of all types of thyroid cancer in the USA of 7.7 per 100 000 person-years, with rates of 11.3 per 100 000 woman-years and 4.1 per 100 000 man-years [1.Aschebrook-Kilfoy B. Ward M.H. Sabra M.M. Thyroid cancer incidence patterns in the United States by histologic type, 1992–2006.Thyroid. 2011; 21: 125-134Crossref PubMed Scopus (318) Google Scholar]. The incidence of papillary thyroid cancer is 5.7 per 100 000 person-years, with rates of 8.8 per 100 000 woman-years and 2.7 per 100 000 man-years [1.Aschebrook-Kilfoy B. Ward M.H. Sabra M.M. Thyroid cancer incidence patterns in the United States by histologic type, 1992–2006.Thyroid. 2011; 21: 125-134Crossref PubMed Scopus (318) Google Scholar]. Among women, papillary thyroid cancer incidence rates are higher among Asians (10.96 per 100 000 woman-years) and lower among blacks (4.9 per 100 000 woman-years). Among men, papillary thyroid cancer incidence rates are higher among whites (3.58 per 100 000 woman-years) and lower among blacks (1.56 per 100 000 woman-years) [1.Aschebrook-Kilfoy B. Ward M.H. Sabra M.M. Thyroid cancer incidence patterns in the United States by histologic type, 1992–2006.Thyroid. 2011; 21: 125-134Crossref PubMed Scopus (318) Google Scholar]. The incidence of follicular thyroid cancer in the USA is 0.82 per 100 000 person-years, with rates of 1.06 per 100 000 woman-years and 0.59 per 100 000 man-years. The incidence of follicular cancer does not vary substantially by race/ethnicity [1.Aschebrook-Kilfoy B. Ward M.H. Sabra M.M. Thyroid cancer incidence patterns in the United States by histologic type, 1992–2006.Thyroid. 2011; 21: 125-134Crossref PubMed Scopus (318) Google Scholar]. The incidence rates of medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC) are 0.11 and 0.21 per 100 000 person-years with no noted substantial differences by race/ethnicity and sex, respectively. An escalating incidence during the last decades all over the globe has been reported [2.Howlader N. Noone A.M. Krapcho M. SEER Cancer Statistics Review, 1975–2008. National Cancer Institute, Bethesda, MD2011http://seer.cancer.gov/csr/1975_2008/Google Scholar]. This phenomenon is mainly due to an increase in micropapillary (<2 cm) histotype, while there is no substantial change in the incidence of the less common histological categories: follicular, medullary and anaplastic cancers. The increase is attributable to better detection of small papillary carcinomas as a result of improved diagnostic accuracy (neck ultrasound, US and fine needle aspiration cytology, FNAC). It is common experience in thyroid cancer referral centers that nearly 60%–80% of thyroid carcinomas detected nowadays are micropapillary thyroid carcinomas (<1 cm in size) carrying an excellent long-term prognosis [3.Leenhardt L. Bernier M.O. Boin-Pineau M.H. et al.Advances in diagnostic practices affect thyroid cancer incidence in France.Eur J Endocrinol. 2004; 150: 133-139Crossref PubMed Scopus (183) Google Scholar]. However, more recently, an increased incidence for all size of thyroid tumor has been reported in the USA. During 1997–2005, the annual percentage change (APC) for primary tumor 4 cm among men (1988–2005: APC 3.7) and women (1988–2005: APC 5.7) [4.Chen A.Y. Jemal A. Ward E.M. Increasing incidence of differentiated thyroid cancer in the United States, 1988–2005.Cancer. 2009; 115: 3801-3807Crossref PubMed Scopus (770) Google Scholar]. These data suggested that increased diagnostic scrutiny is not the only explanation, and environmental influence should also be considered. The only established environmental risk factor for thyroid carcinoma is exposure to ionizing radiation, and the risk, particularly of papillary carcinoma, is greater in subjects of younger age at exposure. An increased incidence of thyroid cancer in children and adolescents was observed in Ukraine, Belarus and certain regions of Russia as early as 4 years after the Chernobyl accident. The pre-Chernobyl incidence of thyroid cancer in Ukrainian children was very low (0.5–1.0 per 1 000 000 children). Following the explosion of the Chernobyl nuclear reactor in 1986, a dramatic increase in the incidence of benign and malignant thyroid tumors (80 times more) was observed in children born or conceived around the time of the accident in a wide area surrounding the reactor [5.Tronko M.D. Bogdanova T.I. Komissarenko I.V. et al.Thyroid carcinoma in children and adolescents in Ukraine after the Chernobyl nuclear accident: statistical data and clinicomorphologic characteristics.Cancer. 1999; 86: 149-156Crossref PubMed Scopus (154) Google Scholar]. Despite increasing incidence, the mortality from thyroid cancer has tended to decline over the last three decades. It is unclear how much of the decline in mortality is due to better diagnosis rather than to improved treatment of thyroid neoplasm. The age-adjusted death rate was 0.5 per 100 000 men and women per year, increasing from 0.1% under age 20%–30% in the seventh and the eighth decades [2.Howlader N. Noone A.M. Krapcho M. SEER Cancer Statistics Review, 1975–2008. National Cancer Institute, Bethesda, MD2011http://seer.cancer.gov/csr/1975_2008/Google Scholar]. Thyroid cancer presents as a thyroid nodule detected by palpation and more often by neck US. While thyroid nodules are common (4%–50% depending on the diagnostic procedures and patients' age) [6.Dean D.S. Gharib H. Epidemiology of Thyroid Nodules.Best Pract Res Clin Endocrinol Metab. 2008; 22: 901-911Crossref PubMed Scopus (408) Google Scholar], thyroid cancer is rare (∼5% of all thyroid nodules). Thyroid US is a widespread technique that is used as a first-line diagnostic procedure for detecting and characterizing nodular thyroid disease (I, A). US features associated with malignancy are hypoechogenicity, microcalcifications, absence of peripheral halo, irregular borders, solid aspect, intranodular blood flow and shape (taller than wide). Each of these patterns taken individually is poorly predictive. When multiple patterns suggestive of malignancy are simultaneously present in a nodule, the specificity of US increases but the sensitivity becomes unacceptably low [7.Pacini F. Schlumberger M. Dralle H. et al.European Thyroid Cancer TaskforceEuropean consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium.Eur J Endocrinol. 2006; 154: 787-803Crossref PubMed Scopus (1640) Google Scholar, 8.Cooper D.S. Doherty G.M. Haugen B.R. et al.American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid CancerRevised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.Thyroid. 2009; 19: 1167-1214Crossref PubMed Scopus (5478) Google Scholar]. Fine needle aspiration cytology (FNAC) is an important technique that is used along with US for the diagnosis of thyroid nodules (III, A). FNAC should be performed in any thyroid nodule >1 cm and in those <1 cm if there is any clinical (history of head and neck irradiation, family history of thyroid cancer, suspicious features at palpation, presence of cervical adenopathy) or ultrasonographic suspicion of malignancy. In the case of multinodular goiter, those with suspicious features at US should be submitted to FNAC. FNAC is a very sensitive tool for the differential diagnosis of benign and malignant nodules although there are limitations: inadequate samples and follicular neoplasia. In the event of inadequate samples, FNAC should be repeated, while in the case of follicular neoplasia, with normal thyroid stimulating hormone (TSH) and 'cold' appearance at thyroid scan, surgery should be considered [7.Pacini F. Schlumberger M. Dralle H. et al.European Thyroid Cancer TaskforceEuropean consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium.Eur J Endocrinol. 2006; 154: 787-803Crossref PubMed Scopus (1640) Google Scholar, 8.Cooper D.S. Doherty G.M. Haugen B.R. et al.American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid CancerRevised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.Thyroid. 2009; 19: 1167-1214Crossref PubMed Scopus (5478) Google Scholar]. The use of various immunohistochemical markers in cytologic samples to differentiate papillary thyroid carcinoma from other follicular-derived lesions of thyroid has been explored during the last years but none of the markers appears to be specific enough to be employed as the diagnostic marker for the cytologic diagnosis of papillary thyroid carcinoma [7.Pacini F. Schlumberger M. Dralle H. et al.European Thyroid Cancer TaskforceEuropean consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium.Eur J Endocrinol. 2006; 154: 787-803Crossref PubMed Scopus (1640) Google Scholar, 8.Cooper D.S. Doherty G.M. Haugen B.R. et al.American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid CancerRevised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.Thyroid. 2009; 19: 1167-1214Crossref PubMed Scopus (5478) Google Scholar]. Recently, it has been reported that by molecular testing for thyroid nodules (BRAF, RAS, RET/PTC and PAX8/PPARγ mutations), the presence of any mutation was a strong indicator of cancer because ∼97% of mutation-positive nodules had malignant diagnosis at histology [9.Nikiforov Y.E. Steward D.L. Robinson-Smith T.M. et al.Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules.J Clin Endocrinol Metab. 2009; 94: 2092-2098Crossref PubMed Scopus (576) Google Scholar, 10.Cantara S. Capezzone M. Marchisotta S. et al.Impact of proto-oncogene mutation detection in cytological specimens from thyroid nodules improves the diagnostic accuracy of cytology.J Clin Endocrinol Metab. 2010; 95: 1365-1369Crossref PubMed Scopus (241) Google Scholar] (III, B). Thyroid function test and thyroglobulin (Tg) measurement are of little help in the diagnosis of thyroid cancer. However, measurement of serum calcitonin computed tomography (CT) is a reliable tool for the diagnosis of the few cases of MTC (5%–7% of all thyroid cancers) and has higher sensitivity compared with FNAC. For this reason, measurement of CT should be an integral part of the diagnostic evaluation of thyroid nodules [7.Pacini F. Schlumberger M. Dralle H. et al.European Thyroid Cancer TaskforceEuropean consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium.Eur J Endocrinol. 2006; 154: 787-803Crossref PubMed Scopus (1640) Google Scholar] (IV, B). The initial treatment of differentiated thyroid carcinoma (DTC) should always be preceded by careful exploration of the neck by US to assess the status of lymph node chains. The initial treatment of DTC is total or near-total thyroidectomy whenever the diagnosis is made before surgery. Less extensive surgical procedures may be accepted in the case of unifocal DTC diagnosed at final histology after surgery performed for benign thyroid disorders, provided that the tumor is small, intrathyroidal and of a favorable histological type (classical papillary or follicular variant of papillary or minimally invasive follicular) (I, A). In the case of widely invasive follicular cancer at final histology, completion thyroidectomy is indicated. The benefit of prophylactic central node dissection in the absence of evidence of nodal disease is controversial. There is no evidence that it improves recurrence or mortality rate, but it permits an accurate staging of the disease that may guide subsequent treatment and follow-up [7.Pacini F. Schlumberger M. Dralle H. et al.European Thyroid Cancer TaskforceEuropean consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium.Eur J Endocrinol. 2006; 154: 787-803Crossref PubMed Scopus (1640) Google Scholar, 8.Cooper D.S. Doherty G.M. Haugen B.R. et al.American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid CancerRevised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.Thyroid. 2009; 19: 1167-1214Crossref PubMed Scopus (5478) Google Scholar] (IV, C). However, it is not indicated in follicular thyroid cancer; compartment-oriented microdissection of lymph nodes should be performed in cases of preoperatively suspected and/or intraoperatively proven lymph node metastases in follicular thyroid cancer (IV, B). In expert hands, surgical complications such as by laryngeal nerve palsy and hypoparathyroidism are extremely rare (<1%–2%) [7.Pacini F. Schlumberger M. Dralle H. et al.European Thyroid Cancer TaskforceEuropean consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium.Eur J Endocrinol. 2006; 154: 787-803Crossref PubMed Scopus (1640) Google Scholar]. Several staging systems have been developed by authoritative centers. Each of these staging systems provides good risk stratification based on data available shortly after initial therapy. The most popular is the American Joint Committee on Cancer/International Union against Cancer TNM staging system based mainly on the extent of tumor and age [11.2009 AJCC Cancer Staging Manua l7th edition New York Springer-VerlagGoogle Scholar]. Although all staging systems are able to predict high or low risk of cancer mortality, they fail to predict the risk of recurrence. To overcome this limitation, both the American Thyroid Association (ATA) and the European Thyroid Association (ETA) have recently published practical guidelines [7.Pacini F. Schlumberger M. Dralle H. et al.European Thyroid Cancer TaskforceEuropean consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium.Eur J Endocrinol. 2006; 154: 787-803Crossref PubMed Scopus (1640) Google Scholar, 8.Cooper D.S. Doherty G.M. Haugen B.R. et al.American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid CancerRevised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.Thyroid. 2009; 19: 1167-1214Crossref PubMed Scopus (5478) Google Scholar] in which they graded the risk of recurrence in three categories of increasing risk on the basis of tumor-related parameters (pTNM and histological variant) integrated with other clinical features, including the result of the post-ablative whole-body scan (WBS) and serum Tg measurement (Table 1).Table 1Risk stratification according to the ETA [7.Pacini F. Schlumberger M. Dralle H. et al.European Thyroid Cancer TaskforceEuropean consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium.Eur J Endocrinol. 2006; 154: 787-803Crossref PubMed Scopus (1640) Google Scholar] and ATA guidelines [8.Cooper D.S. Doherty G.M. Haugen B.R. et al.American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid CancerRevised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.Thyroid. 2009; 19: 1167-1214Crossref PubMed Scopus (5478) Google Scholar]ATA risk stratificationLow riskIntermediate riskHigh risk No local or distant metastasesAll macroscopic tumor has been resectedNo tumor invasion of locoregional tissues or structuresNo aggressive histology or vascular invasionIf 131I was given, no 131I uptake outside the thyroid bed on the post-therapeutic WBSMicroscopic invasion of tumor into the perithyroidal soft tissues at initial surgeryCervical lymph node metastases or131I uptake outside the thyroid bed on the post-therapeutic WBSor Tumor with aggressive histology or vascular invasionMacroscopic tumor invasionIncomplete tumor resectionDistant metastasesThyroglobulinemia out of proportion to what is seen on the post-ablative scanETA risk stratificationVery low riskLow riskHigh risk Complete surgeryNo local or distant metastasesLess than total thyroidectomy Patients with unifocal microcarcinoma (<1 cm) with no extension beyond the thyroid capsule and without lymph node metastasesNo tumor invasion of locoregional tissues or structuresTumor invasion of locoregional tissues or structuresNo aggressive histology or vascular invasionCervical lymph node metastasesDistant metastasesAggressive histology or vascular invasion Open table in a new tab Recent reports have developed the new concept of 'Ongoing Risk Stratification' or 'Delayed Risk Stratification (DRS)', which better define the patient risk on the basis of the results of the initial treatment [12.Tuttle R.M. 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 DRS American Thyroid Association staging system.Thyroid. 2010; 20: 1341-1349Crossref PubMed Scopus (645) Google Scholar, 13.Castagna M.G. Maino F. Cipri C. et al.Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients.Eur J Endocrinol. 2011; 165: 441-446Crossref PubMed Scopus (200) Google Scholar]. This concept is based on the continuous integration of the initial risk stratification (at the time of diagnosis) with the clinical, radiologic and laboratory data becoming available during follow-up. Although the risk stratifications proposed by ATA [8.Cooper D.S. Doherty G.M. Haugen B.R. et al.American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid CancerRevised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.Thyroid. 2009; 19: 1167-1214Crossref PubMed Scopus (5478) Google Scholar] and ETA [7.Pacini F. Schlumberger M. Dralle H. et al.European Thyroid Cancer TaskforceEuropean consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium.Eur J Endocrinol. 2006; 154: 787-803Crossref PubMed Scopus (1640) Google Scholar] are a good starting point for initial decision-making, they are less accurate in predicting the long-term outcome in DTC patients. Indeed, both systems have a very low positive predictive value (PPV) because of the fact that a large number of patients (∼60%) classified as intermediate/high-risk are in complete remission at the end of follow-up [13.Castagna M.G. Maino F. Cipri C. et al.Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients.Eur J Endocrinol. 2011; 165: 441-446Crossref PubMed Scopus (200) Google Scholar]. This drawback is probably due to the lack of consideration of the effects of the initial therapy. When patients are re-stratified according to the results of the 8–12-month control after initial treatment, a significant number of patients who were initially considered (misleadingly) high-risk were re-classified as low-risk and, most interestingly, almost all of these patients continued to be in apparent remission up to the end of follow-up [13.Castagna M.G. Maino F. Cipri C. et al.Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients.Eur J Endocrinol. 2011; 165: 441-446Crossref PubMed Scopus (200) Google Scholar]. This DRS allows modulation of the subsequent follow-up excluding a significant number of intermediate/high-risk patients from unnecessary intensive work-up (IV, C). Surgery is usually followed by the administration of 131I activities aimed at ablating any remnant thyroid tissue and potential microscopic residual tumor. This procedure decreases the risk of locoregional recurrence and facilitates the long-term surveillance based on serum Tg measurement and diagnostic radioiodine WBS. In addition, the high activity of 131I makes it possible to obtain a highly sensitive post-therapeutic WBS. According to several guidelines [7.Pacini F. Schlumberger M. Dralle H. et al.European Thyroid Cancer TaskforceEuropean consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium.Eur J Endocrinol. 2006; 154: 787-803Crossref PubMed Scopus (1640) Google Scholar, 8.Cooper D.S. Doherty G.M. Haugen B.R. et al.American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid CancerRevised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.Thyroid. 2009; 19: 1167-1214Crossref PubMed Scopus (5478) Google Scholar], the recommendations for remnant thyroid ablation are modulated on the basis of risk factors. Radioiodine ablation is indicated in high-risk patients (IV, B), whereas it is not indicated in low-risk patients (IV, D). In patients at intermediate risk radioiodine remnant ablation may be indicated, but the decision must be individualized (Table 2) [7.Pacini F. Schlumberger M. Dralle H. et al.European Thyroid Cancer TaskforceEuropean consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium.Eur J Endocrinol. 2006; 154: 787-803Crossref PubMed Scopus (1640) Google Scholar, 8.Cooper D.S. Doherty G.M. Haugen B.R. et al.American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid CancerRevised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.Thyroid. 2009; 19: 1167-1214Crossref PubMed Scopus (5478) Google Scholar].Table 2Indication for remnant ablative therapy [8.Cooper D.S. Doherty G.M. Haugen B.R. et al.American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid CancerRevised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.Thyroid. 2009; 19: 1167-1214Crossref PubMed Scopus (5478) Google Scholar]RAI is recommendedRAI is not recommendedAll patients with Known distant metastases Documented lymph node metastasesPatients with unifocal cancer <1 cm without other higher risk featuresaHigher risk features: histological subtypes (tall cell, columnar, insular and solid variant as well as poorly DTC and follicular and Hurthle cell cancer), intrathyroidal vascular invasion, gross or microscopic multifocal disease. Gross extrathyroidal extension of the tumor regardless of tumor sizePatients with multifocal cancer when all foci are 2 cm even in the absence of other higher risk featuresaHigher risk features: histological subtypes (tall cell, columnar, insular and solid variant as well as poorly DTC and follicular and Hurthle cell cancer), intrathyroidal vascular invasion, gross or microscopic multifocal disease.a Higher risk features: histological subtypes (tall cell, columnar, insular and solid variant as well as poorly DTC and follicular and Hurthle cell cancer), intrathyroidal vascular invasion, gross or microscopic multifocal disease. Open table in a new tab Effective thyroid ablation requires adequate stimulation by TSH. The method of choice for preparation to perform a radioiodine ablation is based on the administration of recombinant human TSH (rhTSH), while the patient is on levothyroxine (LT4) therapy (I, A). On the basis of several reports [14.Pacini F. Ladenson P.W. Schlumberger M. et al.Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized, controlled study.J Clin Endocrinol. 2006; 91: 926-932Crossref PubMed Scopus (366) Google Scholar, 15.Pilli T. Brianzoni E. Capoccetti F. et al.A comparison of 1850 (50 mCi) and 3700 MBq (100 mCi) 131-iodine administered doses for recombinant thyrotropin-stimulated postoperative thyroid remnant ablation in differentiated thyroid cancer.J Clin Endocrinol Metab. 2007; 92: 3542-3546Crossref PubMed Scopus (144) Google Scholar, 16.Chianelli M. Todino V. Graziano F.M. et al.Low-activity (2.0 GBq; 54 mCi) radioiodine post-surgical remnant ablation in thyroid cancer: comparison between hormone withdrawal and use of rhTSH in low-risk patients.Eur J Endocrinol. 2009; 160: 431-436Crossref PubMed Scopus (73) Google Scholar], the latter procedure is considered the method of choice demonstrating equal efficacy compared with THW but better acceptance from the patients. In addition, in the recent years, it has become increasingly apparent that successful thyroid ablation may be achieved using low activities of 131I (1110–1850 MBq) [15.Pilli T. Brianzoni E. Capoccetti F. et al.A comparison of 1850 (50 mCi) and 3700 MBq (100 mCi) 131-iodine administered doses for recombinant thyrotropin-stimulated postoperative thyroid remnant ablation in differentiated thyroid cancer.J Clin Endocrinol Metab. 2007; 92: 3542-3546Crossref PubMed Scopus (144) Google Scholar, 16.Chianelli M. Todino V. Graziano F.M. et al.Low-activity (2.0 GBq; 54 mCi) radioiodine post-surgical remnant ablation in thyroid cancer: comparison between hormone withdrawal and use of rhTSH in low-risk patients.Eur J Endocrinol. 2009; 160: 431-436Crossref PubMed Scopus (73) Google Scholar] (I, B). Recent studies demonstrate that rhTSH-assisted radioiodine ablative therapy is associated with similar rates of persistent disease and clinically evident recurrence compared with those observed after traditional thyroid hormone withholding (THW) preparation, at least during short-term follow-up [17.Elisei R. Schlumberger M. Driedger A. et al.Follow-up of low-risk differentiated thyroid cancer patients who underwent radioiodine ablation of postsurgical thyroid remnants after either recombinant human thyrotropin or thyroid hormone withdrawal.J Clin Endocrinol Metab. 2009; 94: 4171-4179Crossref PubMed Scopus (66) Google Scholar, 18.Tuttle R.M. Brokhin M. Omry G. et al.Recombinant human TSH-assisted radioactive iodine remnant ablation achieves short-term clinical recurrence rates similar to those of traditional thyroid hormone withdrawal.J Nucl Med. 2008; 49: 764-770Crossref PubMed Scopus (114) Google Scholar]. In addition, preparation with either rhTSH or THW appears to have similar adjuvant therapy effects on small-volume radioiodine-avid (RAI-avid) disease identified outside the thyroid bed at the time of initial radioiodine remnant ablation [15.Pilli T. Brianzoni E. Capoccetti F. et al.A comparison of 1850 (50 mCi) and 3700 MBq (100 mCi) 131-iodine administered doses for recombinant thyrotropin-stimulated postoperative thyroid remnant ablation in differentiated thyroid cancer.J Clin Endocrinol Metab. 2007; 92: 3542-3546Crossref PubMed Scopus (144) Google Scholar, 19.Tuttle R.M. Lopez N. Leboeuf R. et al.Radioactive iodine administered for thyroid remnant ablation following recombinant human thyroid stimulating hormone preparation also has an important adjuvant therapy function.Thyroid. 2010; 20: 257-263Crossref PubMed Scopus (51) Google Scholar]. RAI-avid metastastic disease discovered at the time of rhTSH-stimulated remnant ablation was successfully treated in ∼70% of locoregional lymph nodes [15.Pilli T. Brianzoni E. Capoccetti F. et al.A comparison of 1850 (50 mCi) and 3700 MBq (100 mCi) 131-iodine administered doses for recombinant thyrotropin-stimulated postoperative thyroid remnant ablation in differentiated thyroid cancer.J Clin Endocrinol Metab. 2007; 92: 3542-3546Crossref PubMed Scopus (144) Google Scholar, 19.Tuttle R.M. Lopez N. Leboeuf R. et al.Radioactive iodine administered for thyroid remnant ablation following recombinant human thyroid stimulating hormone preparation also has an important adjuvant therapy function.Thyroid. 2010; 20: 257-263Crossref PubMed Scopus (51) Google Scholar] and in ∼70% of pulmonary micrometastases [19.Tuttle R.M. Lopez N. Leboeuf R. et al.Radioactive iodine administered for thyroid remnant ablation following recombinant human thyroid stimulating hormone preparation also has an important adjuvant therapy function.Thyroid. 2010; 20: 257-263Crossref PubMed Scopus (51) Google Scholar]. In light of these data, the use of rhTSH for post-thyroidectomy 131I ablation represents a safe and effective option for the postoperative management of patients with thyroid cancer. The aim of follow-up is the early discovery and treatment of persistent or recurrent locoregional or distant disease. The large majority of local recurrences develop and are detected in the first 5 years after diagnosis. However, in a minority of cases, local or distant recurrence may develop in late follow-up, even 20 years after the initial treatment. Two to three months afte
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