Introduction
The treatment of thyroid cancer is a controversial field [2]
[3]
[4]
[5]
[6]
[7]. Data from prospective, evidence-based trials on long-term outcome with/without
radioiodine therapy (RIT) are sparse and hard to obtain, because in order to yield
clinically relevant results and to demonstrate the benefit of RIT, a follow-up of
10 years or more is generally needed. Thus, guidelines from several countries differ
in their advice on how to treat patients with differentiated thyroid carcinoma best
[2]
[3]
[4]
[5]
[6]
[7]. Several publications have raised the issue of relevant controversies [8]
[9]
[10]
[11]. The multidisciplinary approach to thyroid cancer care has resulted in the implementation
of dedicated endocrine tumor boards in many specialized centers, recommending suitable
therapy concepts for the individual patient on an interdisciplinary basis. This includes
surgery, nuclear medicine, endocrinology, radiation therapy, pathology and other partners.
For the development of consensus statements or guidelines, it seems advisable to discuss
and also address regional and national differences in thyroid cancer care as well
as epidemiological differences in populations worldwide. Any recommendation needs
to be discussed with the patient who takes the final decision.
Although few developed countries have a persistent deficiency of iodine intake, Germany
is still one of them [12] resulting in a relatively high prevalence of thyroid nodules. Taking into account
the frequency of thyroid nodules in different age groups and demographic data, it
is estimated that about 15 million persons or more are affected in Germany [9]. Only a small fraction of these nodules is malignant with varying estimations of
one malignant nodule in 375 to 1000 benign thyroid nodules. Given the high number
of autonomous and other benign thyroid nodules, diagnostic strategies and therapeutic
recommendations in Germany differ from those of other countries. As an example, thyroid
scintigraphy with pertechnetate is advised for patients with thyroid nodules larger
than 1 cm in diameter to identify autonomous nodules as benign findings [14]. Nodules of under 1 cm are usually observed through follow-up examinations. Fine
needle aspiration biopsy (FNAB) for nodules of less than 1 cm is recommended neither
in Germany [15] nor anywhere else in Europe. Of note, no dramatic increase in papillary thyroid
microcarcinomas (PTMC) has been observed in contrast to the steep increase reported
in the literature from Asian countries but also – to a lesser extent – from the US
[16]. To increase the pretest-likelihood for thyroid cancer, it is considered good practice
in Germany to select nodules for FNAB by demonstration of hypofunctionality (“cold
nodules”) on scintigraphy in combination with suspicious ultrasound features. Regrettably,
owing to the high frequency of thyroid nodules and/or the presence of multiple nodules
in one patient, FNAB before surgery is frequently not performed in Germany. Yet despite
considerable progress in reducing “diagnostic thyroid surgeries”, a substantial fraction
of operations is carried out mainly to rule out malignancy. A current analysis of
a Germany surgery registry showed that among almost 18 000 patients with benign thyroid
histology, 68 % had been referred for “exclusion of malignancy”, and only 12 % of
those had had a previous FNAC [17].
In Germany, about 7000 new cases (5040 women and 2192 men in 2017) of thyroid cancer
are diagnosed each year and differentiated thyroid cancer accounts for more than 90 %
of all thyroid cancers. The age-standardized mortality of thyroid cancer in Germany,
which was initially high in comparison to other countries, approximately halved over
the period 1995–2015. According to figures from the USA and Germany for 2015, the
mortality of DTC is comparable at about 0.3 cases per 100 000. However, the USA is
one of the few countries worldwide with a mortality of thyroid carcinoma that has
increased by about 25 % since the year 2000 [18].
The majority of patients undergoing thyroid surgery in Germany, just as in other iodine-deficient
countries, have benign histopathological findings. From intraoperative frozen sections,
it has recently been shown that the rate of completion surgeries could be considerably
reduced [19]. According to Maneck et al., less than 9465 (15.2 %) out of 62 090 surgical operations
assessed revealed a malignancy [20]. In contrast, taking the SEER (Surveillance, Epidemiology, and End Results) data
into account, about 36 % of thyroid surgeries in the United States result in a DTC
diagnosis, a frequency more than twice as high as that in Germany. Banach et al. published,
that preoperative suspicion of thyroid carcinoma was present in 37 % of German but
in 84 % of American patients [21].
In 2016, Haugen et al. published the guidelines of the American Thyroid Association
(ATA), written predominantly by a group of North American thyroid experts [3]. Though their aim was to give advice on contemporary optimal care of patients with
thyroid cancer, the guidelines had to be classified as S2 since neither a systematic
literature search nor any evidence tables were available.
With European experts holding different views on this issue, a position paper was
published in 2019 contrasting several aspects mainly with respect to the extent of
surgery (lobectomy versus thyroidectomy for PTC ≤ 4 cm) and the potential need for
completion thyroidectomy [6]
[11]. Significant divergence involved ATA 2015's guidance regarding RIT. European panelists
favored a wider use of postoperative radioiodine than did ATA 2015. Rationales included
the modality's association with favorable patient outcomes and generally limited toxicity,
and lack of high-quality evidence supporting a withholding of radioiodine therapy.
European panelists also noted that the ATA 2015 risk-stratification system requires
information sometimes unavailable in everyday practice [6].
The ATA guidelines introduced a dynamic risk model for recurrence based on histopathologic
criteria and molecular analysis such as BRAF mutational status and recommended standard
RIT after surgery only in high-risk patients. Low or intermediate risk groups should
either not have radioiodine at all or should have radioiodine on a selective basis
[3]. However, that recommendation has limited applicability, as it is not entirely clear
from where the authors of the ATA guidelines derived the probability of tumor recurrence
taken as the basis for their risk model. The issue was aggravated further when the
2022 European Thyroid Association (ETA) consensus statement adopted the ATA risk model
without further elaboration and recommended that the decision for postoperative RIT
should be taken based on initial prognostic indicators for thyroid cancer related
death and risk of recurrence. Of note, the authors state that indeed, despite the
inevitable body radiation exposure, the administration of a low activity of RAI has
not been demonstrated to present a risk in terms of secondary cancer or leukemia,
infertility and untoward pregnancy outcomes or other side effects.
In the following, we modify and comment on the recommendations made in the ETA consensus
statement with a special focus on the use of radioiodine. Interdisciplinary evidence-based
S3-guidelines for DTC are currently being developed in Germany, with the aim of providing
specific guidance tailored to the national situation. These guidelines will provide
information in much more detail than the position paper presented here by specialists
in surgery and nuclear medicine.
Recommendation 1 (ETA consensus statement)
The decision for post-operative radioiodine therapy should be taken based on initial
prognostic indicators for thyroid cancer related death and recurrence, including among
others the surgical and pathological report and on the results of serum thyroglobulin
measurements and neck ultrasonography obtained after surgery.
Modified recommendation 1
The decision to proceed with post-operative RIT should be based on the recommendation
of an interdisciplinary tumor board incorporating initial prognostic indicators for
thyroid cancer related death and recurrence, including not only the surgical and pathology
report, and patient age but also the results of postoperative laboratory and imaging
results. The patient should be involved in the decision-making process (“shared decision
making”).
RIT has many aspects that need to be considered both by the treating doctor and the
patient during shared decision making [22]. One aspect is the treatment of occult disease as an adjuvant approach. Here, it
is important to note that the frequency of lymph node metastases is quite high in
thyroid cancer. On histopathologic workup, lymph node metastases are found in approximately
20–80 % of PTC patients [2]
[23] and are increasingly likely to occur in higher T-stage tumors. However, even in
PTMC frequencies of lymph node metastases of 35 % and 57 % have been reported [24]
[25]. Prophylactic lymph node dissection is the gold standard to exclude metastatic lymph
node involvement, but is performed only in certain constellations such as the presence
of suspicious lymph nodes or other high risk factors. Furthermore, the probability
of complications is higher with this procedure than with (stand-alone) thyroidectomy,
and many patients with an incidental finding of thyroid cancer will not have a lymph-node
dissection. Both post-therapeutic imaging after administration of RIT and pre-therapeutic
imaging using radioactive isotopes of iodine provide a highly sensitive staging in
this context and can help to select patients for removal of lymph nodes pre- or post
RIT [26].
We do not agree with the authors of the ETA consensus statement that post-surgical
nonstimulated Tg levels can be used independently in deciding whether to pursue therapeutic
radioiodine administration, especially in patients assigned as low-risk category based
on surgical pathology information. Campenni et al. reported in 570 low- and low-intermediate
risk DTC patients that post-therapeutic radioiodine imaging including SPECT/CT identified
82 patients (14.4 %) who had metastases, 73 patients of which (90.2 %) had nonstimulated
Tg ≤ 1 ng/ml after surgery. Also, 44 patients (54 %) of 82 metastasized patients had
a stimulated Tg ≤ 1 ng/ml [27].
Furthermore, diagnostic postoperative radioiodine imaging can provide important additional
information. In a group of 320 thyroid cancer patients referred for postoperative
RIT, Avram et al. showed that diagnostic imaging with 131I including SPECT/CT after thyroid hormone withdrawal (THW) visualized regional metastases
in 35 % and distant metastases in 8 % of the cases. TNM stage was changed by this
imaging in 4 % of the younger and 25 % of the older patients [25]. In another study by Avram et al., imaging data as well as stimulated thyroglobulin
levels measured at the time of diagnostic postoperative 131I imaging provided information that altered the management of the patients in 29 %
of cases when compared to the initial strategy based on surgical pathology information
and clinical information by itself [28].
Another important aspect of RIT is the psychological impact in terms of assuring patients
of their being free of disease with the prospect of retaining a good quality of life
in the long term [29]
[30]. The data published regarding the outcome of postoperative RIT in low-risk patients
(combination of remnant ablation and adjuvant treatment) showed that patients in this
category can be reassured of a complete treatment response. They also require a less
intense follow-up and fewer imaging procedures [31]. Data published on DTC patients (including those in the low-risk category), who
received RIT after surgery, showed that life expectancy is normal in these patients
except for those with stage IV disease [32]
[33]. Similar data with a sufficiently long follow-up in general but also for Germany
specifically are, however, not available for a more restrictive use of radioiodine.
On the other hand, there is broad consensus that risk-adapted treatment of thyroid
cancer is a desirable goal and patients should not be exposed to any unnecessary therapeutic
procedures. The risk of metastatic spread and recurrence is highly variable in DTC,
with most patients having a good prognosis. Patients should be informed and involved
in shared decision-making, based not only on histopathology and thyroglobulin results,
but also on postoperative radioiodine imaging and the individual need for safety/security
[22].
Recommendation 2 (ETA consensus statement)
The use of I-131 therapy as adjuvant treatment or treatment of known disease is indicated
for patients in the high risk of recurrence category or with known structural disease.
In this setting, high activities (≥ 3700 MBq) of radioiodine are preferred over low
activities.
Modified recommendation 2
The use of I-131 therapy as adjuvant treatment or treatment of known disease is indicated
for patients in the high risk of recurrence category or with known structural disease.
In this setting, high activities (≥ 3700 MBq) of radioiodine are preferred over low
activities. Individual dosimetry may be considered.
We do agree with the authors of ETA consent in this respect. However, evidence is
still lacking on whether a dosimetric approach is superior to a fixed dosing therapy.
From a radiobiological point of view, higher activities are preferred over (fractionated)
lower activities. Dosimetry with diagnostic postoperative radioiodine imaging helps
to avoid exceeding organ-specific dose limits, especially in patients with renal impairment
and diffuse lung metastases.
Recommendation 3 (ETA consensus statement)
In the intermediate-risk category*, RIT therapy may be indicated and should be tailored
according to individual cases.
*patients with 1) microscopic invasion of tumor into the perithyroidal soft tissues;
2) aggressive histology (e. g., tall cell, hobnail variant, columnar cell carcinoma);
3) PTC with vascular invasion; 4) clinical N1 or > 5 pathologic N1 with all N1 < 3 cm
in largest dimension; 5) multifocal papillary microcarcinoma with microscopic invasion
of tumor into the perithyroidal soft tissues and BRAFV600E mutation (if known)
Modified recommendation 3
In the intermediate-risk category, RIT therapy is indicated.
In our view, there is a clear indication for adjuvant RIT therapy in the ATA intermediate
risk group. Evidence from a large retrospective series of patients indicates that
there is a benefit for patients, not only in terms of survival but also in terms of
recurrence.
In 2008, Sawka et al. published a pilot review article on RIT therapy with a total
of 28 publications. With regard to tumor-related mortality, a data pooling of 11 studies
revealed a significant reduction from 3.9 % without to 2.5 % with RIT. With regard
to recurrence-free survival, 5 studies with the largest number of patients (n = 3474)
showed a considerable and significant reduction in risk from 24.2 % without RIT therapy
to 12.5 % with RIT therapy. It should be emphasized that patients with a life expectancy
of 10 or more years had a definite benefit from radioiodine therapy [34].
From 1998–2006 the National Cancer database, USA, contained 21 870 DTC patients with
pT3 N0 M0 or pT1–3 N1 M0. Among 15 418 patients who were treated with radioiodine,
there was a reduction in overall mortality by 29 % compared with 6452 patients who
were not referred to radioiodine therapy. This advantage in favor of radioiodine therapy
was found despite the remarkable fact that the patients who had radioiodine treatment
suffered from more advanced disease: In the radioiodine group, 51 % of the patients
showed multifocal disease versus 47 % in the non-radioiodine group. Both lymph node
metastases (74 % versus 68 %) and R1 resections (19 % versus 15 %) were more frequent
in the radioiodine group, respectively. To stress this fact, even despite the less
favorable patient population, RIT was able to convert the pre-RIT situation in that
group into a decreased post-treatment mortality [35].
Unlike the authors of the ETA consensus, we do not see the role of RIT in BRAF-mutated
as controversial – but as clearly indicated. The literature cited by the authors does
support their conclusion as well. The cited study by Sabra at al. was performed in
43 patients with DTC who were included because of initially known distant metastases;
those authors come to the conclusion that tumor genotype does not influence the response
to RIT therapy [36]. However, in the second publication cited where Liu et al. assessed recurrent DTC,
the results cannot be readily transferred to the postoperative use of RIT [37]. Even in the setting of recurrent BRAF-mutated DTC (after initial RIT-therapy),
37 % of cases still showed uptake of RIT, indicating a potential benefit from RIT
therapy. Besides, there is also published evidence to show that BRAF status does not
negatively influence response to RIT therapy [38]
[39].
We also disagree that postoperative thyroglobulin levels and neck ultrasound are sufficient
to exclude metastatic DTC, especially in the intermediate-risk group (see comment
to recommendation 1) [40].
Recommendation 4 (ETA consensus statement)
In low-risk patients§, the benefit of I-131 therapy is a matter of intensive scientific
debate and the decision on whether to perform radioiodine therapy should be based
on the presence of individual risk modifiers.
§ patients with 1) intrathyroidal PTC without vascular invasion, with or without small
volume lymph node metastases (clinical N0 or ≤ 5 pathologic N1, all < 0.2 cm in largest
dimension); 2) intrathyroidal encapsulated follicular variant of papillary thyroid
cancer or intrathyroidal well differentiated follicular cancer with capsular or minor
vascular invasion (< 4 vessels involved); 3) intrathyroidal papillary microcarcinomas
that are either BRAF wild type or BRAF mutated (if known)
Modified recommendation 4
In low-risk patients, RIT therapy should be performed in patients at stages pT1b-2,
N0–1; in stage pT1a RIT may be performed but under consideration of additional risk
modifiers (e. g. multifocality, aggressive histology, BRAF mutation).
Here, we also refer to our comment on recommendation 1. Of note, we do not see a clear
dichotomy between ablative and adjuvant RIT therapy, since the therapeutic administration
of RIT always has an adjuvant component to treat metastatic disease, as well as a
diagnostic intention (resulting in a more adequate tumor staging). Indeed, there has
been an intense scientific debate over RIT in low-risk patients. In our view, large
patient collectives and long follow-up periods are needed in order to assess the value
of RIT in this category in terms of overall survival and recurrence free survival.
Currently, there are two ongoing trials assessing the non-inferiority of no radioiodine
treatment as compared to low dose RIT in a low-risk population: ESTIMABL2 and ION
(NCT01837745 and NCT01398085). First results of ESTIMABL2 have been published. Here,
the administration of 1.1 GB I-131 was compared to no RIT. In a first assessment with
3 years of follow-up, no difference in terms of recurrence rate in 776 patients was
revealed by this study [41]
[42]. Unfortunately, the patients are only followed for 5 years which, for data from
the analysis of cancer registries, is too short according to Sawka et al. [34]. In our view, the activity of 1.1 GBq of I-131 is also too low for adjuvant treatment.
The use of this activity is even controversial for the purpose of ablation (see comment
on recommendation 6). The authors of the ETA consensus themselves state that “a tendency
for larger groups and longer follow-up duration seems to be loosely associated with
showing an advantage of giving RIT”. In our view, the data from retrospective series
with very large patient collectives and a long follow-up are in favor of RIT even
in a low-risk population and it is therefore not justified to generally withhold this
treatment from these patients. Adam et al. showed that radioiodine therapy led to
a significantly improved overall survival in 61 775 patients from the National Cancer
Database with PTC diameters of 1.0–2.0 cm and 2.1–4.0 cm [43]. Attributing the average mortality to a value of 1.0, mortality decreased in the
RIT group to a value of 0.77 (95 % CI 0.68–0.87) in stage pT1b and to a value of 0.86
(95 % CI 0.76–0.98) in stage pT2. The clinical benefit of RIT therapy was higher than
the influence of the extent of the surgical resection.
In an assessment of the Surveillance, Epidemiology, and End Results (SEER) database
over the years 1973–2009 with 61 049 patients, the omission of RIT increased disease-specific
mortality. For patients in group pT2 N0 M0 and < 45 years of age, there was a significant
increase of the hazard ratio for death of 1.3 in patients who had not received RIT
(p < 0.002) [44]. In another study from Hong Kong with 855 patients recurrent-free survival increased
from 82.5 % to 95 % after 10 years when including radioiodine in the therapeutic concept
[45].
In addition, as mentioned in the comment to recommendation 1, posttherapeutic radioiodine
imaging provides valuable information in terms of a highly specific and sensitive
staging tool of great value for assuring the patient.
The authors of the ETA statement also clearly oppose RIT in papillary microcarcinoma
(< 1 cm, uni- or multi-focal), in the absence of other higher-risk features. The cited
study by Hänscheid et al. does not seem to address this topic at all [46]. The second publication mentioned reflects a joint statement of the ATA, EANM, SNMMI
and ETA on controversies, consensus, and collaboration in the use of RIT in differentiated
thyroid cancer [3]. A recommendation not to use RIT in tumors smaller than 1 cm is nowhere to be found
in this consensus, but instead, it is mentioned that “some authors report a benefit
of giving RIT even to patients with non-metastasized microcarcinomas, whereas other
groups find no benefit.” In the light of this statement, it would seem justified to
discuss not only the benefits but also the potential side effects of RIT in papillary
microcarcinoma with the patient in the framework of shared decision-making; risk factors,
such as i. e. multifocality, aggressive histology or nonincidental finding [47] should be weighted together with the patient’s expectations. In minimally invasive
follicular thyroid cancer without vascular invasion, we see a limited value of RIT
irrespective of the size due to the good prognosis of this entity. However, recurrences
were also seen in this group, most likely due to missed vessel infiltration.
The authors of the ETA consensus state that, even if no RIT is given after surgery,
recurrences can be treated very successfully later on. However, no respective literature
is cited in the consensus paper to support this hypothesis. In addition, and we ourselves
are not aware of any larger retrospective or even prospective study in support of
this approach.
Recommendation 5 (ETA consensus statement)
Recombinant human TSH during l-T4 treatment should be the preferred method of preparation
for RIT administration.
Modified recommendation 5
Recombinant human TSH and thyroid hormone withdrawal (THW) can both be used for patient
preparation for RIT therapy.
Recombinant human TSH (rhTSH) is an important development for the treatment of patients
with thyroid carcinoma reducing symptoms of hypothyroidism and has provided patient
benefit in terms of quality of life. Though usually well tolerated, clinical experience
shows that some patients complain about muscle pain, fatigue, headache, malaise, sickness
and vomiting after injections of rhTSH. The choice of preparation method (THW vs.
rhTSH) strongly depends on the regionally pre-established treatment schemes as well
as on patient and tumor stage specific factors. Previously published data reveals
that in the setting of thyroid remnant ablation, rhTSH and THW stimulation are equivalent,
because normal thyroid tissue usually shows a high expression of NIS and no longer
intervals of TSH stimulation are necessary to reach an adequate uptake of RAI.
However, according to Hänscheid et.al., preparation for ablative RIT with THW can
lead to higher radiation doses to the blood and the whole body as compared to rhTSH
[46]. In this prospective randomized, multicentric international licensing study for
rhTSH, THW was performed until a blood level of TSH reached 25 mU/L corresponding
to approx. 4 weeks of thyroid hormone withdrawal [46]. In keeping with these results, Bacher et al. showed in a retrospective study in
a larger number of patients that an increase in radiation absorbed dose is detectable
in patients with an interval of hypothyroidism of 4 or more weeks between surgery
and RIT. When a shorter time interval between 18–25 days was chosen, no difference
in radiation absorbed dose was seen, though the two preparation regimens were equally
effective [49]. In the setting of adjuvant treatment, which is the preferred treatment in many
patients, the situation concerning the preferred method for preparation is more complex.
The adjuvant aspect of RIT was first acknowledged, after the period during which the
registration studies for rhTSH were performed. There is therefore no clear data available
in the literature to recommend for or against a specific preparation method, and the
registration of rhTSH covers its use in an adjuvant setting.
Recommendation 6 (ETA consensus statement)
Activities of 1110 MBq are equally effective as higher activities for ablation of
presumably benign thyroid remnants.
Modified recommendation 6
Activities of 1–3.7 GBq may be chosen for ablative/adjuvant treatment, if there is
no strong suspicion of residual tumor or of distant metastases. Activities of 1.85–3.7 GBq
are favoured under the aspect of adjuvant RIT.
In our opinion, even when labeled as ablative, RIT always has adjuvant aspects, given
the high prevalence of lymph node metastases [9]
[51]. Even for the goal of ablation, the data does not, in our view, support a clear
preference for 1.1 GBq I-131 over higher activities.
Two prospective randomized trials – HiLo and ESTIMABL – compared the effectiveness of “radioiodine ablation” with either hypothyroidism
or recombinant TSH (rhTSH) using 1.1 GBq (30 mCi) or 3.7 GBq (100 mCi) of radioiodine
[48]
[50]. They came to the conclusion that the two methods of stimulation are equally effective
and stated that 1.1 GBq is not inferior to 3.7 GBq I-131. Both studies included low-risk
patients and excluded aggressive histologic subtypes. Of note, neither study questioned
the use of radioiodine for the treatment of thyroid cancer.
In the HiLo study [48] there was a 6 % lower success rate in the rhTSH group with 1.1 GBq (84.3 %) in comparison
to 3.7 GBq (90.2 %) of radioiodine, which resulted in twice as many second radioiodine
treatments in the low risk versus high-risk group. A total of 21 patients (9.5 %)
receiving low-dose radioiodine were given a subsequent second therapeutic activity,
as compared with 9 patients (4.1 %) receiving high-dose radioiodine (p = 0.02). Second
activities were more than 4 GBq of radioiodine. After a median follow-up of 13 months
(with ≥ 24 months of follow-up in 21 % of patients), six cases with recurrence were
detected (three in each radioiodine-dose group) according to a combination of results
from ultrasonography, fine-needle aspiration, and computed tomography [48].
Another aspect appears noteworthy: In the HiLo study 99 mTc-pertechnetate scintigraphy was performed prior to RIT therapy to visualize thyroid
remnants and only 2.3 % of patients had a large remnant. This might explain why ablation
was successful in 182 of 214 patients (85.0 %) in the group receiving low-dose radioiodine
versus 184 of 207 patients (88.9 %) in the group receiving the high therapeutic activity.
In the ESTIMABL study [50], persistent disease after surgery was identified in 27/752 patients (3.6 %) through
the use of post-ablation total-body scanning (14 patients), post-ablation total-body
scanning and neck ultrasonography (8 patients), or neck ultrasonography only (5 patients).
It is one of the tasks of nuclear medicine to identify this small group of patients
who require advanced therapeutic skills for treatment of persistent disease.
The authors of the ETA consensus correctly cite a recent German publication showing
a higher DTC-related mortality in low-and high-risk patients treated with low activities
at initial RIT (≤ 2 GBq. I-131) when patients were at least 45 years of age at diagnosis,
as well as a higher recurrence rate in older high-risk patients without distant metastases
[33]. From our point of view, the treatment activity in this ablative/adjuvant setting
should be adapted according to individual risk modifiers including postoperative scintigraphic
imaging (see comment on recommendation 1 and 7).
Recommendation 7 (ETA consensus statement)
Whenever a decision to perform post-operative RIT therapy needs to be taken, a diagnostic
scan is not routinely required.
Modified recommendation 7
A postoperative diagnostic functional scan can be helpful as it has been shown to
allow individualized patient management.
We are not certain what the authors of the ETA consensus mean by “Whenever a decision
to perform post-operative RIT needs to be taken”. A decision, for or against a distinct
diagnostic and/or therapeutic approach, has always to be made. However, we assume
that the authors are not in favor of a diagnostic functional scan prior to RIT therapy.
No statement on how to proceed, if RIT is NOT performed, is to be found anywhere in
the consensus.
As mentioned in the comment on recommendation 1, postoperative functional imaging
using radioisotopes may change the postoperative clinical management prior to therapeutic
RIT administration [51]. Functional imaging is an option to further stratify patients into groups such as
those in need of additional lymph node dissection owing to pronounced lymph node involvement,
those requiring a higher radioiodine activity, especially in the presence of detectable
distant metastases, or those needing lower RIT activities in the case of non-detectable
tumor manifestations with minimal thyroid remnants. As mentioned in the ETA consensus,
histological information as well as thyroglobulin levels and ultrasound can also be
used in this context, although their levels of sensitivity are significantly limited.
Moreover, in patients with known persistent disease, diagnostic radioiodine imaging
allows subsequent RIT therapy to be tailored through dosimetry. Using 123I/124I or even 99 mTc (as used in a major phase III trial [48]), stunning, which is mentioned as a limitation in the consensus, may be reduced
or even prevented. Stunning itself is the subject of intense debate. 123I, which avoids this phenomenon, is readily available in Germany and most countries
within Europe, as is 99 mTc. In contrast, 124I is limited to just a few specialist centers.
Recommendation 8 (ETA consensus statement)
A low-iodine diet may be prescribed but its utility is not demonstrated unequivocally.
Any iodine-containing drug should be avoided.
Modified recommendation 8
A low-iodine diet should be followed for two weeks prior to RIT. Iodine-containing
drugs should be avoided.
Avoidance of high stable iodine levels reduces the transport of iodine into thyroid
cells significantly, which is important for minimizing interference with RIT uptake.
We also consider this diet to be a minor burden for patients in Germany. A study conducted
by Pluijmen et al. in 120 patients showed that a low-iodine diet decreased the 24-h
urinary iodine excretion by 83 %; at the same time radioiodine uptake in thyroid remnants
increased by 65 % (p < 0.001) as compared to controls. The efficacy of RIT treatment
was found to be better in the low-iodine group with a successful ablation in 65 %
compared to 48 % patients in the control arm (p < 0.001) [52]
