Eur J Nucl Med Mol Imaging (2010) 37:276283 DOI 10.

1007/s00259-009-1315-6

ORIGINAL ARTICLE

No survival difference after successful 131I ablation between patients with initially low-risk and high-risk differentiated thyroid cancer
Frederik Anton Verburg & Marcel P. M. Stokkel & Christian Dren & Robbert B. T. Verkooijen & Uwe Mder & Johannes W. van Isselt & Robert J. Marlowe & Johannes W. Smit & Christoph Reiners & Markus Luster

Received: 3 June 2009 / Accepted: 23 October 2009 / Published online: 29 November 2009 # Springer-Verlag 2009

Abstract Purpose To compare disease-specific survival and recurrencefree survival (RFS) after successful 131I ablation in patients with differentiated thyroid carcinoma (DTC) between those defined before ablation as low-risk and those defined as highrisk according to the European Thyroid Association 2006 consensus statement.
F. A. Verburg (*) : C. Dren : C. Reiners Department of Nuclear Medicine, University of Wrzburg, Oberdrrbacher Strasse 6, Wrzburg 97080, Germany e-mail: verburg_e@klinik.uni-wuerzburg.de F. A. Verburg : J. W. van Isselt Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands M. P. M. Stokkel : R. B. T. Verkooijen Department of Radiology, Division of Nuclear Medicine, Leiden University Medical Center, Leiden, The Netherlands U. Mder Comprehensive Cancer Center, University of Wrzburg, Wrzburg, Germany R. J. Marlowe Spencer-Fontayne Corporation, Jersey City, NJ, USA J. W. Smit Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands M. Luster Department of Nuclear Medicine, University of Ulm, Ulm, Germany

Methods Retrospective data from three university hospitals were pooled. Of 2009 consecutive patients receiving ablation, 509 were identified as successfully ablated based on both undetectable stimulated serum thyroglobulin in the absence of antithyroglobulin antibodies and a negative diagnostic whole-body scan in a follow-up examination conducted 8.14.6 months after ablation. Of these 509 patients, 169 were defined as high-risk. Results After a mean follow-up of 8164 months (range 4 306 months), only three patients had died of DTC, rendering assessment of disease-specific survival differences impossible. Of the 509 patients, 12 (2.4%) developed a recurrence a mean 35 months (range 1259 months) after ablation. RFS for the duration of follow-up was 96.6% according to the KaplanMeier method. RFS did not differ between high-risk and lowrisk patients (p=0.68). RFS differed slightly but significantly between those with papillary and those with follicular thyroid carcinoma (p=0.03) and between those aged 45 years those aged >45 years at diagnosis (p=0.018). Conclusion After (near) total thyroidectomy and successful 131 I ablation, RFS does not differ between patients classified as high-risk and those classified as low-risk based on TNM stage at diagnosis. Consequently, the follow-up protocol should be determined on the basis of the result of initial treatment rather than on the initial tumour classification. Keywords 131I Ablation . Differentiated thyroid cancer . Risk stratification . Recurrence . Survival . Prognostic factors

Introduction Even though in all patients except those with papillary microcarcinoma, initial therapy for differentiated thyroid

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carcinoma (DTC) consists of total thyroidectomy and 131I ablation, the recommended long-term follow-up strategies differ markedly depending on disease stage at diagnosis. Recent guidelines and consensus reports on the diagnosis and therapy of DTC, such as the American Thyroid Association guidelines [1] and several consensus statements [24], differ in their definitions of high-risk and low-risk patients. However, their risk stratification is largely based on the initial pTNM stage. Low-risk patients are usually defined as those having thyroid cancers confined to the thyroid gland, without evidence of lymph node or distant metastases. In contrast, high-risk patients are usually defined as those with locally invasive or metastatic disease. Initial therapy is usually evaluated 612 months after ablation. The evaluation includes neck ultrasonography, measurement of thyroglobulin (Tg) levels after thyroid-stimulating hormone (TSH) stimulation and 131I whole-body scintigraphy (WBS). Most guidelines advise that when no evidence of tumour is found at that evaluation, further TSH-stimulated evaluation can be omitted in low-risk patients. Rather, recommended follow-up in such patients consists of at least annual Tg measurement during thyroid hormone therapy. For patients with high-risk carcinomas, a more intensive follow-up is recommended, with regular TSH-stimulated Tg measurements, irrespective of the outcome of initial therapy. The aim of this study was to investigate whether patient stratification into high-risk or low-risk according to initial tumour staging predicted disease-specific mortality or tumour recurrence after successful ablation and to assess whether follow-up recommendations should differ between the two groups.

For all patients, the TNM stage was initially determined according to the 5th edition of the Union International Contre le Cancer/American Joint Committee on Cancer TNM staging system [5], as not all data required for staging according to the 6th edition [6] were available for patients treated before 2002. For the purposes of risk group determination, the original N stage was adjusted according to the results of the postablation WBS (rxWBS): patients originally classified as N0/Nx were restaged to N1 if lymph node metastases were visible on rxWBS. Patients originally classified as Nx were classified as N0 if no lymph node metastases were visible. Successful ablation was defined as undetectable TSHstimulated Tg and a concurrent absence of 131I uptake on diagnostic WBS (dxWBS) during the first TSH stimulation after 131I ablation; any visually discernible uptake in the thyroid bed was considered pathological both for the purpose of this study and for clinical purposes (in all participating centres, any such uptake led to an additional course of 131I therapy). Additionally, for a patient to be defined as successfully ablated, no other therapeutic interventions (e.g. surgery) were allowed to have taken place between 131I ablation and the first WBS. As a consequence of the inclusion criteria, all patients in this study were by definition disease-free after surgery and ablation. Recurrence was defined as any of the following events occurring during follow-up: Cytological/histological evidence of disease. Detectable Tg levels in the absence of anti-Tg antibodies (TgAb) during thyroid hormone replacement or after TSH stimulation. Foci of uptake on 131I scintigraphy.

Patients, materials and methods Patients Hospitals Three university hospitals participated in this study: the University Clinic Wrzburg (UKW), in Germany, and the Leiden University Medical Center (LUMC) and the University Medical Center Utrecht (UMCU) University Clinic, both in The Netherlands. All three hospitals are tertiary referral centres for postsurgical 131I treatment of DTC patients. Definitions High-risk patients were defined according to the 2006 European Thyroid Association consensus. This consensus classifies patients as at high-risk of recurrence all those with (1) a primary tumour of 4 cm in diameter, (2) a primary tumour extending beyond the thyroid capsule, or (3) nodal or distant metastases. All other patients were considered to be at low risk of recurrence [2]. From among 2009 consecutive patients treated in the inclusion period, 509 with DTC who had undergone (near) total thyroidectomy and subsequently received successful 131 I ablation as defined above were identified (295 from the UKW, 102 from the UMCU and 112 from the LUMC). The patients charts were reviewed retrospectively. The patients included at the UKW received 131I ablation from January 1980 up to and including December 2005, patients at UMCU from January 1990 up to and including March 2005, and patients at the LUMC from January 1990 up to and including October 2005. Follow-up data were acquired up to and including December 2006 in all centres. Initial treatment All patients with successful 131I ablation were included, regardless of the ablation protocol that was used, even

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though some protocols showed a higher success rate than others [710]. All patients received at least a (near) total thyroidectomy, with some patients also receiving a central lymph node dissection. Lateral lymph node dissection was performed in those with preoperatively known lymph node metastases. Depending on the protocol, histology, remnant size and tumour stage, the administered ablation activities ranged from 1,100 MBq 131I in patients with large thyroid remnants to 7,400 MBq in patients with extensive locally invasive or metastatic disease [8, 11]. After ablation, all patients received TSH-suppressive levothyroxine treatment to maintain serum TSH at 0.1 mIU/l. Laboratory analyses Because different Tg assays were used over the years and in three centres, for this study, classification of Tg levels as undetectable was based on the lower detection limit of the assay used in a given follow-up examination rather than on a single- or multicentre cut-off value for all assays. The presence of TgAb was investigated either through direct measurement or through determination of Tg recovery rates. Since undetectable serum Tg levels cannot be interpreted as evidence of remission [4, 12, 13] in the presence of TgAb, patients were excluded from the study in the presence of Tg antibody positivity or if Tg recovery was insufficient. Follow-up after ablation All patients had a TSH-stimulated follow-up evaluation 3 months to 1 year after 131I ablation. Serum TSH levels were elevated either by levothyroxine withdrawal, or, in more recent years, by intramuscular injection of recombinant human TSH (rhTSH). During TSH stimulation, Tg levels were measured and dxWBS using 185370 MBq 131I was performed. All patients received at least one more TSH-stimulated evaluation within 5 years of ablation. During follow-up, patients were evaluated by yearly ultrasonography of the neck and Tg measurements during TSH-suppressive therapy or by repeated 131I scintigraphy in selected cases. The use of ultrasonography in addition to Tg measurement and dxWBS differed between centres: at UKW, ultrasonography was performed in all patients from before 1990, whereas until about 2004/2005, at LUMC and UMCU ultrasonography was performed only in selected patients. For these reasons, the sonographic findings were not used as a criterion for ablation success or recurrence in this study; however, cytological/histological evidence of disease, which was used as such a criterion, was sometimes obtained by investigation as a result of suspicious sonographic findings.

Statistical analysis Statistical analysis was performed using SPSS 16.0 (SPSS, Chicago, IL). Survival times were calculated using the Kaplan-Meier method [14]. Differences in survival times were assessed with a log-rank test. Statistical significance was defined as p<0.05.

Results Patient details are presented in Table 1. The mean follow-up time was 8164 months (median 60 months, range 4 306 months) after ablation. The first follow-up, i.e. evaluation of ablation success, was performed on average 8.14.6 months (median 6.4 months) after 131I ablation. Disease-specific survival During follow-up, three patients (0.6%) died of DTC 63, 107 and 130 months after ablation and 49, 60 and 71 months after detection of DTC recurrence. Two of these patients had a high-risk tumour (T4N0M0), and one a lowrisk tumour (T2N0M0). Due to this very limited number of events, no analysis of thyroid cancer-specific survival differences was possible. Recurrence-free survival Of the 509 patients, 12 (2.4%) developed a recurrence after a mean interval of 35 months (range 1259 months) after ablation, of whom five were high-risk and seven low-risk. The overall 5-year and 10-year recurrence-free survivals (RFS) calculated according to the Kaplan-Meier method were both 96.61.0% (Fig. 1). No recurrences were observed 60 months after ablation. High-risk patients did not show a higher recurrence rate than low-risk patients: the long-term survival-adjusted risk of recurrence was 3.41.3% in low-risk patients and 3.71.7% in high-risk patients (p=0.68; Fig. 2). Potential prognostic variables for RFS There was no difference in RFS among the participating centres (p=0.31). RFS was not influenced by gender (p=0.33), T stage (p=0.72), or the presence of lymph-node metastases (p=0.54). In contrast, patients aged 45 years at diagnosis had a slightly, but significantly, lower 5-year RFS rate than patients aged <45 years at diagnosis (94.41.8% vs. 98.40.9%, p=0.018; Fig. 3). Patients with papillary thyroid cancer had a significantly higher 5-year RFS rate than those with follicular histology (98.00.9% vs. 93.32.5%; p=0.03; Fig. 4).

Eur J Nucl Med Mol Imaging (2010) 37:276283 Table 1 Selected patient characteristics Variable Overall DTC patient population during the study period (n=2009) Study population (patients with successful ablation, n=509)a No. (%) of patients 271 (53%) 238 (47%) 367 (72%) 139 (27%) 3 (1%) 5 (1%) 69 (14%) 291 (57%) 70 (14%) 50 (10%) 24 (5%) 424 (83%) 85 (17%) 509 (100%) 320 (63%) 169 (33%) 20 (4%) 459 (90%) 50 (10%)

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No. (%) of patients Age <45 years Age 45 years Histology Papillary thyroid carcinoma Follicular thyroid carcinoma Unknown T stageb T0 T1 T2 T3 T4 Tx N stageb N0 N1 M stageb M0 M1 Stratification for recurrence riskc Low risk High risk Unknown Extrathyroidal tumour invasion No invasion Invasion N/A not available.
a b c

No. of recurrences 3 9 5 7 0 0 1 6 2 3 0 11 1 12 7 5 0 9 3

952 (47%) 1057 (53%) 1483 (74%) 515 (26%) 11 (<1%) 10 (<1%) 419 (21%) 877 (44%) 275 (14%) 338 (17%) 90 (4%) 1560 (78%) 449 (22%) 1824 (91%) 185 (9%) N/A N/A N/A 1671 (83%) 338 (17%)

Mean age 44.2 years. TNM system, 5th edition. Low-risk/high-risk stratification defined according to the 2006 ETA consensus statement [2].

Recurrence detection In 7 of the 12 patients with recurrence, the recurrence was first detected by TSH-suppressed Tg measurement, and in 5 by TSH-stimulated Tg measurement. In only 1 of the 12 patients was a concurrent 131I dxWBS positive; in none of the patients was the recurrence first detected by 131I WBS. In 6 of the 12 patients, an anatomical substrate for the recurrence was found: four of these individuals had distant metastases, and two had a local recurrence. In the remaining six patients, we were unable to identify the source of the elevated Tg levels: one of these patients died of cardiac arrest before a diagnosis could be made, one patient received an empirical therapeutic activity and from that time had undetectable Tg levels, and four patients at

the time of this report remained under surveillance without signs or symptoms of active disease other than mildly elevated Tg levels during suppression or TSH stimulation. In no patient was a spontaneous remission of Tg elevation, i.e. a decrease to undetectable levels without therapeutic intervention, seen once the criteria for recurrence were met.

Discussion This study sought to determine whether the division of patients into groups at high or low risk of DTC recurrence according to initial staging, the approach recommended in most guidelines, retains prognostic utility after successful ablation. Related to this question is the issue of whether

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Fig. 1 Overall recurrence-free survival

postablation follow-up recommendations should differ between the two groups [13]. We showed that after successful 131I ablation, patients initially classified as high-risk have a recurrence risk comparable to that of patients initially categorized as low-risk. Consequently, the follow-up protocol in low-risk and high-risk patients need not differ after successful ablation.

Fig. 3 Recurrence-free survival in patients <45 and 45 years of age at the time of initial treatment of DTC. The difference between the two curves is statistically significant (p=0.018)

Although previous studies have shown similar results, the present investigation is the largest published study yet to address this issue. Even more importantly, our study provides multicentre validation of the concept of successful ablation re-setting recurrence risk despite intercenter variations in

Fig. 2 Recurrence-free survival in initially high-risk and low-risk patients. The difference between the patient groups is not statistically significant (p=0.68)

Fig. 4 Recurrence-free survival in patients with papillary or follicular thyroid carcinoma. The difference between the two curves is statistically significant (p=0.03)

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ablation protocols. Kloos and Mazzaferri [15] studied a relatively small group of patients with a negative first TSHstimulated follow-up (n=68) who were treated in a single centre. They reported a recurrence rate of about 2% in patients with rhTSH-stimulated Tg levels <0.5 ng/ml in the first evaluation after initial therapy. A limitation of the Kloos and Mazzaferri study was a relatively brief follow-up of a maximum of 5 years, which contrasts with a maximum follow-up of 25 years in some of our patients. A recent study by Tuttle et al. [16], which included both successfully and unsuccessfully ablated patients, found that recurrences all occurred within the first 5 years after ablation, as was the case in our study. However, the recurrence rate found by Tuttle et al. was 8% in patients ablated under rhTSH versus 12% in patients ablated after levothyroxine withdrawal. A potential explanation for the higher recurrence rates found by Tuttle et al. lies in these investigators different criteria for successful treatment: a patient was considered to have no clinical evidence of disease if suppressed Tg levels were below 2 ng/ml and stimulated Tg levels were below 10 ng/ ml. These criteria led to a substantial number of patients being classified as disease-free who according to our criteria, would be considered to have persistent disease; this may in turn have led to a higher number of recurrences, many of which would have been considered progression of existing disease according to the criteria of the present study. A study by Pacini et al. [17] concluded that the combination of clinical examination, TSH-stimulated Tgmeasurement and neck ultrasonography would suffice to monitor DTC patients, and that 131I WBS did not reveal any additional findings except for persistent thyroid bed uptake. Pacini et al. later confirmed these findings in another study [18]. Robbins et al. [19] largely concurred with the opinion of Pacini et al., but only for patients with at least one negative WBS: in such patients, further follow-up WBS did not yield significant information. Our finding of a limited value of dxWBS for follow-up of DTC after the initial posttherapy evaluation is in agreement with both of these studies. In the first study of Pacini et al., the long-term recurrence-free rate (89.5%) for patients with a negative first stimulated Tg measurement was somewhat lower than in our study. This may possibly be explained by different inclusion criteria: Pacini et al. defined successful ablation based only on undetectable stimulated serum Tg at the first evaluation after initial therapy, whereas we defined successful ablation based on both undetectable stimulated Tg and negative dxWBS at the first evaluation. Our finding that patients with follicular thyroid carcinoma had a higher recurrence rate than patients with papillary carcinoma could be seen as contrasting with another recent study from our group. In that other study, we found no difference in tumour-specific survival between patients with these histologies when adjustment was made for TNM stage at

diagnosis [20]. However, when no adjustment was made for TNM stage, our earlier study also noted a significant difference in overall survival, with patients with follicular carcinoma showing a considerably worse prognosis. Possibly the generally more advanced stage of presentation of follicular carcinoma lies at the heart of the lower RFS for patients with this histotype although initial stage itself did not obviously influence relapse rates in the present study. Another explanation could reside in differences in tumour biology, for example, in expression or trafficking of the sodium-iodine symporter (NIS), which is necessary for successful 131I therapy. The number of recurrences in the present series, however, was too low to preclude any statistically useful analysis of smaller subgroups, e.g. by disease stage or degree of NIS expression within each histotype, even had fresh tumour material been available for the latter analysis. As alluded to above, the analysis in this study was to a certain extent hampered by the very low number of recurrences (n=12, about 2.4%). The low number of events markedly reduced the power of any statistical examination of differences in RFS and made impossible a meaningful multivariate analysis of independent influences on RFS. Only 25% of all patients treated for DTC in the inclusion period fulfilled this studys criteria for successful ablation. Several factors contributed to this relatively low proportion of patients. Firstly, most T1 patients did not receive 131I ablation; only those with multifocal carcinoma or unfavourable histology did. Secondly, the UKW followed a two-step ablation protocol in the 1980s and early 1990s. Under this protocol, a low 131I activity was administered for initial ablation of large thyroid remnants in patients without metastatic disease after which a second 131I activity was required to achieve successful ablation in nearly all patients. A similar protocol was used at the LUMC. Additionally, all patients with distant metastases required multiple therapies. Our study excluded all patients receiving any treatment between the first ablative therapy and the initial follow-up examination. Lastly, a considerable number of patients received postablation follow-up exclusively at local hospitals, or were otherwise lost to follow-up at our centres. It also must be stressed, that due to the inclusion criteria the high-risk group in this study was a selection of patients responding favourably to 131I. The exclusion of patients with distant metastases led to a study group with an a priori good prognosis. Over the years and in the different participating centres, many different immunoassay kits were used for Tg measurement. As Tg levels cannot be reliably compared quantitatively between kits [12], we opted in this study for a qualitative assessment of Tg levels (detectable versus undetectable for the given assay). Also, the differences in follow-up methods inherent to the multicentre nature and

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Eur J Nucl Med Mol Imaging (2010) 37:276283 2. Pacini F, Schlumberger M, Dralle H, Elisei R, Smit JW, Wiersinga W. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 2006;154:787803. 3. Schlumberger M, Berg G, Cohen O, Duntas L, Jamar F, Jarzab B, et al. Follow-up of low-risk patients with differentiated thyroid carcinoma: a European perspective. Eur J Endocrinol 2004;150: 10512. 4. Mazzaferri EL, Robbins RJ, Spencer CA, Braverman LE, Pacini F, Wartofsky L, et al. A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma. J Clin Endocrinol Metab 2003;88: 143341. 5. Sobin LH, Wittekind C, editors. TNM classification of malignant tumours. 5th ed. Berlin: Springer; 1997. 6. Sobin LH, Wittekind C, editors. TNM classification of malignant tumours. 6th ed. New York: Wiley-Liss; 2002. 7. Verburg FA, Verkooijen R, Stokkel M, van Isselt J. The success of 131I ablation in thyroid cancer patients is significantly reduced after a diagnostic activity of 40 MBq 131I. Nuklearmedizin 2009;48:13842. 8. Verkooijen RB, Verburg FA, van Isselt JW, Lips CJ, Smit JW, Stokkel MP. The success rate of I-131 ablation in differentiated thyroid cancer: comparison of uptake-related and fixed-dose strategies. Eur J Endocrinol 2008;159:3017. 9. Verkooijen RB, Stokkel MP, Smit JW, Pauwels EK. Radioiodine131 in differentiated thyroid cancer: a retrospective analysis of an uptake-related ablation strategy. Eur J Nucl Med Mol Imaging 2004;31:499506. 10. Verburg FA, de Keizer B, Lips CJ, Zelissen PM, de Klerk JM. Prognostic significance of successful ablation with radioiodine of differentiated thyroid cancer patients. Eur J Endocrinol 2005;152: 337. 11. de Klerk JM, de Keizer B, Zelissen PM, Lips CM, Koppeschaar HP. Fixed dosage of 131I for remnant ablation in patients with differentiated thyroid carcinoma without pre-ablative diagnostic 131I scintigraphy. Nucl Med Commun 2000;21:52932. 12. Spencer CA, Bergoglio LM, Kazarosyan M, Fatemi S, LoPresti JS. Clinical impact of thyroglobulin (Tg) and Tg autoantibody method differences on the management of patients with differentiated thyroid carcinomas. J Clin Endocrinol Metab 2005;90: 556675. 13. Spencer CA. Challenges of serum thyroglobulin (Tg) measurement in the presence of Tg autoantibodies. J Clin Endocrinol Metab 2004;89:37024. 14. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:45781. 15. Kloos RT, Mazzaferri EL. A single recombinant human thyrotropin-stimulated serum thyroglobulin measurement predicts differentiated thyroid carcinoma metastases three to five years later. J Clin Endocrinol Metab 2005;90:504757. 16. Tuttle RM, Brokhin M, Omry G, Martorella AJ, Larson SM, Grewal RK, 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;49:76470. 17. Pacini F, Capezzone M, Elisei R, Ceccarelli C, Taddei D, Pinchera A. Diagnostic 131-iodine whole-body scan may be avoided in thyroid cancer patients who have undetectable stimulated serum tg levels after initial treatment. J Clin Endocrinol Metab 2002;87:1499501. 18. Pacini F, Molinaro E, Castagna MG, Agate L, Elisei R, Ceccarelli C, et al. Recombinant human thyrotropin-stimulated serum thyroglobulin combined with neck ultrasonography has the highest sensitivity in monitoring differentiated thyroid carcinoma. J Clin Endocrinol Metab 2003;88:366873.

long time-frame of this study, might have introduced a bias. Especially the use of thyroid hormone withdrawal vs. the use of rhTSH theoretically could be of concern. As previous studies have shown that rhTSH produces qualitatively, but not quantitatively, equal results to thyroid hormone withdrawal [21, 22], we again opted for the qualitative approach in setting our criteria for successful ablation with regard to Tg levels and the presence of 131I uptake. The use of different ablation protocols at three participating centres may appear to be a weakness of the study. We argue, however, that the uniformly favourable outcomes at these independently operating facilities make the study findings and conclusions even more robust. A worthwhile area for further research would be the course of DTC in patients who require multiple treatments to become disease-free; however, as these patients by definition had unsuccessful ablation, they remained outside the scope of the present study. Our study has interesting clinical implications. It demonstrated that successful ablation is a positive predictor of a highly favourable prognosis in patients with DTC. This supports the continuation of adjuvant radioiodine administration in DTC patients [23] a practice which has recently come under scrutiny [24]. Perhaps the most important finding was that a high-risk classification at initial staging is converted to a low-risk status following successful 131I ablation. This observation strongly supports the concept of ongoing risk assessment throughout the patients treatment and follow-up that was recently proposed by Tuttle et al. [25]. Our study also clearly showed that a high-risk stratification before treatment should be discarded once the results of initial treatment have been evaluated, since patients with successful ablation have a very favourable prognosis regardless of their initial staging. Conclusion After successful ablation, established by negative serum Tg levels in patients without interfering TgAb and by negative 131 I dxWBS, RFS rates in patients with DTC are high, even in those individuals who initially were classified as highrisk based on tumour classification at diagnosis. Risk stratification should therefore be based on the assessment of evidence of tumour (Tg and 131I WBS uptake) in the first follow-up examination after ablation. 131I WBS is useful for restratification of risk, but thereafter generally does not yield additional diagnostic information.

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