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Received: 25 July 2018    Revised: 22 November 2018    Accepted: 26 January 2019

DOI: 10.1111/coa.13300

ORIGINAL ARTICLE

Evaluating the predicted impact of changes to the AJCC/

TMN staging system for differentiated thyroid cancer (DTC):
A prospective observational study of patients in South East
Scotland

Kate Hulse1  | Adam Williamson1 | Fraser W. Gibb2 | Brendan Conn3 | Iain J. Nixon1

1
Department of Otolaryngology, St
John’s Hospital, NHS Lothian, Livingston,
Edinburgh, UK
2
Edinburgh Centre for Endocrinology &
Diabetes, Royal Infirmary of Edinburgh,
Edinburgh, UK
3
Department of Pathology, Western General
Hospital, NHS Lothian, Edinburgh, UK
Correspondence
Kate Hulse, Department of Otolaryngology,
St John’s Hospital, Livingston, NHS Lothian,
Edinburgh, UK
Email: kate.hulse@nhs.net
Abstract
Objectives: To assess the impact of the eighth edition AJCC/TMN staging system on
patients with new diagnoses of differentiated thyroid cancers presenting to our re‐
gional multidisciplinary team meetings.
Design: We analysed Endocrine Cancer MDT meeting records from 2009 to 2015 to
identify all patients in the region presenting with a new diagnosis of differentiated
thyroid cancer. We re‐staged patients according to the eighth edition AJCC/TNM
staging classification and analysed the survival outcomes of patients in each stage
under the seventh and eighth systems.
Setting: Tertiary referral centre in South East Scotland (NHS Lothian).
Participants: Three hundred and sixty‐one patients were newly diagnosed with DTC
within South East Scotland during the study period and met our inclusion criteria.
Main outcome measures: Disease‐specific mortality at any time during follow‐up.
Results: In total, 119 of 361 (33%) patients were re‐staged when the eighth edition
AJCC/TMN system was applied. The number of patients classified as having ad‐
vanced stage (III/IV) disease fell from 76 (21%) to 8 (2%). The most common reason
for down‐staging was re‐classification of tumour size, a factor in 96 (80.7%) down‐
staged patients. The five‐year disease‐specific survival of the cohort overall was
98%. Overall, 7 (1.9%) thyroid cancer–related deaths occurred during follow‐up,
three of whom were down‐staged.
Conclusions: On implementation of the eighth edition of the AJCC/TMN staging sys‐
tem, we expect many patients who would previously have been considered to have
advanced thyroid cancer will now be classified as early stage. This will accurately re‐
flect their excellent survival outcomes.

1 | I NTRO D U C TI O N trend in increasing incidence of thyroid cancer is not unique to

1.1 | Background
In 1995, there were 127 new diagnoses of thyroid cancer in
Scotland; in 2015, this figure was 294—a 130% increase.1 This
Scotland, a similar sharp rise in incidence has been observed
globally over the last few decades. 2 There is ongoing speculation
about why this should be the case. A commonly held opinion is
the increasing incidence reflects enhanced diagnosis of previously
subclinical thyroid neoplasms (eg papillary microcarcinomas) as

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© 2019 John Wiley & Sons Ltd Clinical Otolaryngology. 2019;44:330–335.
HULSE et al. |
      331

a result of greater use of ultrasound, fine‐needle aspiration and

cross‐sectional imaging. 3 Despite the increased incidence of thy‐
Keypoints
roid cancer, mortality rates from differentiated subtypes have
• The updated system (8th ed.) for differentiated thyroid
remained static. The prognosis for differentiated thyroid cancer
cancer (DTC) staging was introduced in Jan 2018.
(DTC) is generally excellent although varies according to patients’
• When classified according to the new system, the vast
age at presentation, histology and tumour stage.4
majority of patients will have early stage (I/II) disease.
The 7th edition American Joint Committee on Cancer (AJCC)/tu‐
• The resultant down‐grading of DTC stage is largely ap‐
mour‐node‐metastases (TNM) staging system5 has been used since
propriate and reflects patients’ excellent prognosis.
2009 to predict the disease‐specific survival of patients with thyroid
cancer. This system has recently been updated, and all cases from
January 2018 onwards should be classified according to the AJCC/ significant in terms of prognosis.10,11 Therefore in the 8th edition,
6
TMN 8th edition staging system. The changes defined in the new only gross extra‐thyroidal extension (eg extension into strap mus‐
system are intended to better delineate low‐ and high‐risk patients cles or major neck structures) is considered significant. This means
to help inform management decisions. that older patients (aged over 55 years at presentation) with min‐
In the 7th edition system, patients were initially divided into low‐ imal extra‐thyroidal extension will be re‐staged as T1 or T2 in the
and high‐risk groups according to age—the cut‐off being 45 years old updated system. A summary of all the changes to the staging from
at time of diagnosis. All patients under 45 had stage I disease unless the 7th to the 8th edition, adapted from a 2017 publication by
they had distant metastases, in which case they had stage II disease; Tuttle et al can be seen in Table 1.
only older patients could have advanced stage (III/IV) disease. The
purpose of this age‐based division was to reflect the excellent out‐
1.2 | Objectives
comes of young patients with thyroid cancer. The cut‐off was chosen
to be at age 45 out of convenience as it represents approximately Our aim was to assess the impact of the 8th edition AJCC/TMN
the median age of patients presenting with DTC in most historical staging system on patients with new diagnoses of differentiated thy‐
datasets. In the 8th edition of the AJCC/TMN staging system, the roid cancers presenting to our regional multidisciplinary team (MDT)
age cut‐off has been increased to 55 years. This adjustment has been meetings. Primarily, we wanted to know how many patients would
introduced in an attempt to prevent overstaging of older patients be re‐staged and how this would impact the prognosis associated
with low‐risk tumours and also to provide a more realistic prognosis with each stage group.
for those who remain in high‐risk groups.7,8
In addition to the age‐based change to staging, there have
2 | M ATE R I A L S A N D M E TH O DS
been several adjustments to the way tumour spread and lymph
node status are classified.9 For example, in the 7th edition AJCC/
2.1 | Study design
TMN staging system, patients aged over 45 who had tumours with
any degree of extra‐thyroidal extension were at least T3; however, This was a prospective observational study. The study was con‐
several studies have shown that minimal extension is not clinically ducted in a tertiary centre in South East Scotland (NHS Lothian).

TA B L E 1   Comparison of the 7th and 8th edition staging system

7th Edition—Age <45 8th Edition—Age <55

Stage I All patients without distant metastases All patients without distant metastases
Stage II Distant metastases Distant metastases

7th Edition—Age ≥45 8th Edition—Age ≥55

Stage I ≤2 cm tumour and ≤4 cm tumour and

Confined to thyroid gland Confined to thyroid gland (excluding minimal ETE† )
Stage II 2‐4 cm tumour and >4 cm tumour or
Confined to thyroid gland Central/lateral neck lymph nodes or
Gross ETE into strap muscles
Stage III >4 cm tumour or Any tumour with gross ETE into subcutaneous tissue, larynx,
Minimal ETE or trachea, oesophagus or recurrent laryngeal nerve
Central/lateral neck lymph nodes
Stage IV Gross ETE or Any tumour with gross ETE into pre‐vertebral fascia or
Lateral neck lymph nodes or encasing major vessels or
Distant metastasis Distant metastasis
†
ETE, extra‐thyroid extension.
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332       HULSE et al.

We analysed Endocrine Cancer MDT meeting records from 2009 to 3 | R E S U LT S

2015 to identify all patients in the region presenting with a new di‐
agnosis of differentiated thyroid cancer (papillary or follicular), con‐ Three hundred and seventy patients were newly diagnosed with
firmed by histopathology. DTC within South East Scotland during the study period 2009‐2015.
Nine patients were excluded from the analysis leaving a total sample
size of 361 patients. Regarding the excluded patients, three were
2.2 | Participants
found to have anaplastic variant disease and the remainder had in‐
We excluded any patients with poorly differentiated tumour histol‐ adequate pathology available to complete re‐staging.
ogy, those presenting with recurrent disease and patients without The median age at presentation was 48 (range 16‐86 years). One
an available pathology report. We used patients’ Community Health hundred and fifty‐two (42%) patients were aged under 45 years at
Index (CHI) number, a unique identifier, to search for pathology re‐ presentation, and a further 81 (22%) patients were aged between 45
sults and clinical notes on the NHS Lothian electronic records sys‐ and 54 years. Demographic and clinic characteristics of the cohort
tem. Follow‐up was terminated at the time of patients’ death or the are shown in Table 2. The median follow‐up was 60 months (range
last date patients’ records were checked. 23‐105 months).
Eighty‐seven (24%) and 121 (34%) of patients had a primary left
and right hemithyroidectomy, respectively; 131 (36.3%) had a total
2.3 | Variables
thyroidectomy, and a further 17 patients had a total thyroidectomy
We extracted the following variables for each subject: name, gen‐ plus selective neck dissection primarily. Two patients died from met‐
der, age at presentation, TNM stage, 7th edition AJCC/pTNM stage, astatic disease after biopsy‐proven malignancy but before they had
index side, primary surgery, subsequent surgery, index side histol‐ any operative management—therefore, their pT and pN stages were
ogy, size of tumour (largest if multicentric), histological features not determined (pTxNxM1). One hundred and sixty of 211 (75.8%)
(extra‐thyroidal extension and lymphovascular invasion), survival, patients who had a thyroid lobectomy primarily went on to have
cause of death and months lived since diagnosis. completion surgery. Thirty‐five of 50 (70%) of the patients who had
thyroid lobectomy alone had stage T1aN0M0 disease.
Figure 1 demonstrates the shift in stages between the 7th and
2.4 | Statistical methods
8th staging systems. In total, 119 of 361 (33%) patients were re‐
We analysed patients’ pathology reports and imaging to re‐stage staged when the 8th edition AJCC/TMN system was applied. The
them according to the 8th edition AJCC/TNM staging classification. number of patients classified as having advanced stage (III/IV) dis‐
We then analysed outcomes of patients in each stage under the 7th ease fell from 76 (21%) to 8 (2%). The reason for down‐staging is out‐
and 8th systems to assess the impact of the change. Kaplan‐Meier lined in Table 3; the total number is greater than the sample size as
plots were produced to visualise mortality according to stage, and some patients were down‐staged for more than one reason. Tumour
the log‐rank test was used for survival analysis. size is classified differently in the 8th edition staging system, and this
is the most common reason for patients’ stage to be reduced—being
TA B L E 2   Demographics and clinical patient characteristics
a factor in 96 (80.7%) down‐staged patients.
Variable N = 361 Overall, 15 of 361 (4.2%) of patients died during follow‐up, 7
(1.9%) deaths were related to thyroid cancer. The 5‐year disease‐
Age Median (range) 48 (range 16‐86)
specific survival of the cohort overall was 98%. The outcomes of
Gender Male 78 (21.6%)
patients in each stage as per the 7th and 8th edition classification
Female 283 (78.4%)
are shown in Figure 2A and B. Three patients who were down‐
Histology Papillary 258 (71.5%) staged died of their disease during our follow‐up period; one moved
Follicular 103 (28.5%) from stage III to stage II, one from IV to III and one from IV to II.
pT 1a 102 (28.3%) Comparison of the 5‐year DSS of stage I/II disease using the 7th and
1b 42 (11.6%) 8th staging systems was 99.6% and 99.1%, P = 0.428, respectively.
2 115 (31.9%)
3 87 (24.1%)
4 | D I S CU S S I O N
4 13 (3.6%)
X 2 (0.55%) 4.1 | Synopsis of key findings
pN X/0 303 (83.9%)
In this study, we found that large numbers of patients will be as‐
1a 21 (5.8%)
signed a lower stage following the introduction of the 8th edition
1b 32 (8.9%)
AJCC/TMN staging system. Using the new classification, patients
M 0 350 (97.0%)
with advanced (stages III and IV) disease make up a tiny fraction of
1 11 (3.0%)
thyroid cancers (2%). We expect to see a significant rise in stage I
HULSE et al. |
      333

F I G U R E 1   Alluvial plot demonstrating

the movement of patients between stages
with classified with the 7th (left) versus
8th (right) editions [Colour figure can be
viewed at wileyonlinelibrary.com]

TA B L E 3   Reason for down‐staging an international cohort of patients. Applying a change in age cut‐off
alone led to the down‐staging of 12% of patients, with 9% mov‐
Number down‐staged % of down‐
Variable due to variable staged N = 119 ing from “advanced” stage III or IV disease to stage I or II disease. 5
By applying the additional factors that have been changed in the
Age 45‐54 50 42
updated AJCC system, such as pathological features of primary dis‐
Tumour size 2‐4 cm 70 59
ease and lymph node status, it appears the effect size will be even
Tumour size >4 cm 26 22
more significant. In our cohort, the primary reason patients were
Central/lateral lymph 37 31
down‐staged was tumour size. Previously, a patient aged over 45
nodes
with a T1a/b or T2 N0M0 tumour between 2 and 4 cm in size was
Minimal extra‐thyroi‐ 32 27
stage II and those with tumours greater than 4 cm were stage III or
dal extension
above, whereas in the new system only tumours >4 cm are classified
as stage II.
disease and significant reduction in advanced stage disease in our A comparative study by Shteinshnaider et al found that of 102
MDT once the updated classification system is applied. Although patients with (7th edition) stage III/IV disease, only 11 (10.1%) re‐
our results suggest an improved discrimination between stages mained “advanced” stage after re‐classification.12 This result is sup‐
using the 8th edition, the low event rate limits the conclusions that ported by our findings; in our cohort, 8 of 76 (11%) of stage III/IV
can be drawn. There were no disease‐specific deaths in any patients patients remained “advanced” stage. The paper highlights a statis‐
down‐staged to stage I which suggests that their risk is not being tically significant increase in disease‐specific mortality in stage I‐II
under‐estimated. patients following re‐staging—from 0 of 331 (0%) to 6 of 421 (1.4%)
patient when staged with the 7th and 8th edition classification, re‐
spectively. However, in our cohort, 1 of 285 patients in stage I‐II
4.2 | Comparison with other studies
had a disease‐specific death before re‐staging compared to 3 of 353,
A 2016 multi‐institutional paper validated changing the age cut‐off resulting in a 5‐year DSS of 99.6% vs 99.1%, respectively, P = 0.428.
from 45 to 55 for risk stratification of DTC thyroid cancer patients in Again, low event rates limit the conclusions that can be drawn.
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334       HULSE et al.
F I G U R E 2   Top, Kaplan‐Meier plot by group according to 7th
edition staging. 5‐year disease‐specific survival shown (%). Bottom,
Kaplan‐Meier plot by group according to 8th edition staging 5‐year
disease‐specific survival shown (%) [Colour figure can be viewed at
wileyonlinelibrary.com]
Our 7‐year experience of managing differentiated thyroid can‐
cer demonstrated a 29% rate of follicular carcinoma. This rate is
significantly higher than many international groups in the USA and
Far East. In our unit, all thyroid cancers are reported in accordance
with the recommendations and minimum data set of the Royal
College of Pathologists. All cancer cases (slides and reports) are
further reviewed by a second consultant pathologist prior to pre‐
sentation at the Endocrine MDT for quality assurance purposes as
part of a standard operating procedure. All members of the endo‐
crine pathology team regularly attend meetings and slide seminars
of the United Kingdom Endocrine Pathology Society to ensure our
practice, in this most challenging of pathology disciplines, is in line
with that of other departments nationwide. The vast majority of
follicular thyroid cancer diagnosed in this institution is minimally
invasive follicular carcinoma. The biggest challenge in these cases
is assessment for the presence of capsular‐vascular invasion rather
than differentiation from FVPTC (although this can be challenging
in itself); it is therefore unlikely that we are diagnosing FTC where
we should in fact be diagnosing FVPTC. Widely invasive follicular
cancer is much less common. The reasons for this difference are
therefore unclear. However, a recent paper by Craig et al reporting
a long‐term experience in Scotland reported a 36% rate of follicular
carcinoma in their cohort,13 suggesting that there may indeed be a
different distribution of disease in the UK in comparison with other
international cohorts.
4.3 | Clinical applicability of the study
In total, 3 of 119 (2.5%) patients who were down‐staged later died
of metastatic disease. The patient who moved from stage IV to stage
II had ambiguous tumour pathology, which was reported as likely
metastatic papillary carcinoma but possible high‐grade squamous
cell carcinoma. They also died just 5 months after initial surgery,
suggesting either the presence of particularly aggressive disease
or pre‐existing metastases which were not detected at initial stag‐
ing. Clinicians need to be aware that previous studies have shown
that a small cohort of down‐graded patients may remain at high risk
of mortality.7 A larger sample size is required to reliably comment
on survival outcomes given the scarcity of thyroid cancer‐related
deaths.
International guidelines on the management of thyroid can‐
cer have also been updated. The most recent American Thyroid
Association (ATA)14 and the British Thyroid Association (BTA)15
guidelines both suggest thyroid lobectomy alone may be sufficient
to treat tumours less than 4 cm contained to the thyroid gland. For
small tumours without adverse risk factors—such as angioinvasion
and multifocality—lobectomy is reported to have similar outcomes
as total thyroidectomy; however, current evidence is limited to ret‐
rospective studies.16 In our cohort, 35 patients with T1aN0M0 tu‐
mours were treated with lobectomy alone (±radioiodine) and none of
these patients had a disease‐specific death during follow‐up. Longer
term follow‐up is required to determine their rates of disease recur‐
rence and related morbidity.
4.4 | Strengths of the study
There have been no previous studies assessing the impact of all as‐
pects of the new thyroid cancer staging system on UK patients. Our
cohort includes patients from across South East Scotland, present‐
ing to multiple centres, and we believe our findings should be rel‐
evant to other centres nationally and internationally. A strength of
the study is our ability to accurately re‐classify patients according to
all the pathological features dictated in the staging tool using original
pathology reports. We did not include the small number of patients
where this was not possible due to the unavailability of pathology.
We re‐classified all patients presenting to the regional MDT with
DTC over a 6‐year period. However, clearly this study has limitations.
HULSE et al.
Numbers are relatively small, particularly when considering disease‐
specific survival in differentiated thyroid cancer when the event rate
is low. Although we report a median follow‐up period of 5 years, this
may not capture all disease‐related deaths even in patients present‐
ing to MDT with advanced and metastatic disease.17 Despite these
limitations, our results suggest that a significant change in stage dis‐
tribution will be associated with the change in AJCC staging system.
Whether the change to stage will mean a more conservative ap‐
proach to management and follow‐up in the future remains unclear.
5 | CO N C LU S I O N
On implementation of the updated (8th) edition of the AJCC/TMN
staging system for thyroid cancer, we expect the vast majority of
patients have stage I and II disease. Many patients who would pre‐
viously have been considered to have advanced disease will now
be considered to have early‐stage disease. This new stage will
accurately reflect their excellent survival outcomes.
6 | E TH I C A L CO N S I D E R ATI O N S
The study received approval from both the NHS Lothian Caldicott
Guardian and the local research ethics group, and was waived from
full ethical approval (study number 16113).
C O N FL I C T S O F I N T E R E S T
The authors have stated explicitly that there are no conflicts of
interest in connection with this article.
ORCID
Kate Hulse  https://orcid.org/0000-0003-2445-0279
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How to cite this article: Hulse K, Williamson A, Gibb FW,
Conn B, Nixon IJ. Evaluating the predicted impact of changes
to the AJCC/TMN staging system for differentiated thyroid
cancer (DTC): A prospective observational study of patients
in South East Scotland. Clin Otolaryngol. 2019;44:330–335.
https://doi.org/10.1111/coa.13300