Economic Evaluation

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The Economic Cost of Thyroid Cancer in France and the Corresponding

Share Associated With Treatment of Overdiagnosed Cases
Mengmeng Li, PhD,* Filip Meheus, PhD,* Stephanie Polazzi, MD, Patricia Delafosse, PhD, Françoise Borson-Chazot, MD,
Arnaud Seigneurin, MD, Raphael Simon, MSc, Jean-Damien Combes, PhD, Luigino Dal Maso, PhD, Marc Colonna, PhD,
Antoine Duclos, PhD, Salvatore Vaccarella, PhD, on behalf of the The Thyroid Cancer Group FRANCIM

A B S T R A C T

Objectives: Thyroid cancer incidence in France has increased rapidly in recent decades. Most of this increase has been
attributed to overdiagnosis, the major consequence of which is overtreatment. We aimed to estimate the cost of thyroid
cancer management in France and the corresponding cost proportion attributable to the treatment of overdiagnosed cases.
Methods: Multiple data sources were integrated: the mean cost per patient with thyroid cancer was estimated by using the
Echantillon Généraliste des Bénéficiaires data set; thyroid cancer cases attributable to overdiagnosis were estimated for 21
departments using data from the French network of cancer registries and extrapolated to the whole country; medical records
from 6 departments were used to refine the diagnosis and care pathway.
Results: Between 2011 and 2015, 33 911 women and 10 846 men in France were estimated to be diagnosed of thyroid cancer,
with mean cost per capita of V6248. Among those treated, 8114 to 14 925 women and 1465 to 3626 men were due to
overdiagnosis. The total cost of thyroid cancer patient management was V203.5 million (V154.3 million for women and
V49.3 million for men), of which between V59.9 million (or 29.4% of the total cost, lower bound) and V115.9 million (or 56.9%
of the total cost, upper bound) attributable to treatment of overdiagnosed cases.
Conclusions: The management of thyroid cancer represents not only a relevant clinical and public health problem in France
but also a potentially important economic burden. Overdiagnosis and corresponding associated treatments play an important
role on the total costs of thyroid cancer management.

Keywords: economic costs, overdiagnosis, overtreatment, thyroid cancer.

VALUE HEALTH. 2023; 26(8):1175–1182

Introduction surgical complications, radioactive iodine treatment, lifelong

The incidence of thyroid cancer in France has increased rapidly
in recent decades,1,2 and thyroid cancer has become the fifth most
commonly diagnosed cancer in women in the country.1,3 Similar
patterns have also been observed in many other countries
worldwide,4-6 characterized by geographical heterogeneity and
accompanied by relatively stable or declining mortality rates.7 A
substantial decrease of the age at diagnosis is also a notable
characteristic observed globally, putting an increased number of
individuals, particularly women, at risk of being diagnosed at
young adulthood or at middle age.8 These specific epidemiological
features reflect in large part overdiagnosis, given the relative
recent possibility to detect indolent tumors known to exist in the
thyroid gland through intensive surveillance with ultrasonogra-
phy and other sensitive diagnostic techniques.
Individuals who are diagnosed of thyroid cancer undergo
treatments, such as total or partial thyroidectomy, possible
thyroid replacement hormone therapy, and periodic monitoring,
and in addition, they are also subject to the health-related quality
of life of a cancer diagnosis and to financial hardship.9-11 The most
recent international and national guidelines recommend against
screening for thyroid cancer in asymptomatic adult populations
(free from specific risk factors) and suggest to use a more con-
servative approach, with a de-escalating strategy in the manage-
ment of the disease.12,13
The economic cost associated with the management of a pa-
tient with thyroid cancer varies across different health systems
and over time14-19 and may also include substantial out-of-
pockets payments20 and indirect costs21 incurred by the pa-
tients. Nevertheless, the total economic cost of thyroid cancer
management that needs to be sustained by the health system has
certainly grown considerably, in parallel with the growing number
of individuals who are diagnosed and who live from a relatively
young age after a diagnosis of thyroid cancer.

*Mengmeng Li and Filip Meheus are joint first authors.

1098-3015/$36.00 - see front matter Copyright ª 2023, International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc.
1176 VALUE IN HEALTH
In this context, it is important to estimate not only the overall
cost of thyroid cancer management but also the possible reduction
in costs that may be expected by reducing treatments in in-
dividuals who have been overdiagnosed. To support these objec-
tives, we integrate several data sources to estimate the economic
costs of thyroid cancer in France from the perspective of the
healthcare system in the period 2011 to 2015, as well as estimate
the magnitude and costs of treatment of overdiagnosed cases.
Methods
Overview
The first step was to estimate the mean cost per patient with
thyroid cancer using a data set representative of the population in
France, the Generalist Sample of Beneficiaries (the “Echantillon
Généraliste des Bénéficiaires” [EGB]). Second, we used cancer
registry data from the French network of cancer registries
(FRANCIM) to estimate the number of newly diagnosed thyroid
cancer cases in 21 departments of France and applied to these data
a previously developed epidemiological method to estimate
overdiagnosis at the population level. Third, we further integrated
complementary information collected from medical records in
some departments on incidentally discovered thyroid cancers, to
adjust the epidemiological assessment and to provide an estima-
tion of the number of overdiagnosed cases that were subsequently
treated. Finally, the estimated mean individual costs were thus
applied to the total number of thyroid cancer cases and to the
corresponding number of overtreated cases.
Mean Cost per Patient With Thyroid Cancer
EGB data set
The costing study was conducted for the period 2012 to 2016
from the perspective of the French healthcare system using
reimbursement claims data obtained from the Generalist Sample
of Beneficiaries (the EGB). Established in 2005, EGB is a nationally
representative random sample of 1/97th of beneficiaries from the
national health insurance interscheme information system (the
“Système National d’Information Inter Régimes de l’Assurance
Maladie”) with data for 660 000 individuals.22 The database
contains anonymous information on demographics and reim-
bursed medical claims from both public and private providers for
all health insurance schemes in France, including information on
consultations, medications, medical and paramedical procedures,
laboratory tests, and other examinations. It does not include ex-
penses that are not eligible for reimbursement such as over-the-
counter drugs.23 The diagnosis of the patient is not recorded in
the EGB database unless the patient was hospitalized or is eligible
for full cost recovery due to a severe chronic illness such as cancer.
In the case of hospitalization, the diagnosis of the patient is
specified in the hospital discharge summary using the Interna-
tional Classification of Diseases 10th revision (ICD-10).
Study participants
Adult patients aged 18 years and older who underwent a full or
partial thyroidectomy for thyroid cancer in metropolitan France
between January 1, 2012, and December 31, 2016, were included in
the study. The first hospital stay for the surgical procedure was
considered as the index date, and patients were identified using
ICD-10 codes C73 (malignant neoplasm of the thyroid) and D09.3
(carcinoma in situ of thyroid or other endocrine glands). Patients
were excluded if there were incorrect data to follow the care
pathway or had one of the following in the year before the index
date: a thyroid surgery, a diagnosis of thyroid cancer, a session
AUGUST 2023
with a speech therapist, and a code of long-term illness of cancer
with ICD-10 C73 (Appendix Fig. 1 in Supplemental Materials found
at https://doi.org/10.1016/j.jval.2023.02.016).
Variables collection
For each patient, we collected information on all procedures
and healthcare claims related to the hospital stay and surgical
procedure (the index), for 12 months preceding the index to
capture costs related to consultations and diagnosis, and for 24
months after the index to document the follow-up period and
costs related to surveillance and complications (Fig. 1). For the
index, data were collected on the age and sex of the patient, the
year and type of surgery (partial or full thyroidectomy), the type of
hospital (university or other), the length of stay, and the
diagnosis-related group cost. The latter includes all medical costs
related to the inpatient stay and the surgical procedure (surgery,
anesthesia, and pathology fees). Information on care practices
related to thyroid cancer for the time periods before and after the
index date to identify activities in the EGB related to thyroid
cancer were informed by the French guidelines on the manage-
ment of thyroid nodules and on radioactive iodine therapy and
molecular imaging.24,25
Data analysis
Continuous variables were summarized using means and
standard deviations, and medians and interquartile ranges. Cate-
gorical variables were represented as counts and percentages. The
mean cost per patient was estimated as the total cost divided by
the number of patients with thyroid cancer included in the EGB
study. Costs are presented by time period and procedure, by
gender, and for 3 age categories (18-44, 45-64, and 65 years and
older).
Thyroid Cancer Cases and Overdiagnosis Estimation in 21
Departments of France
We obtained thyroid cancer incidence data from the FRANCIM
for the period 2011 to 2015 for 21 administrative areas (ie, “de-
partments”), covering 22.7% of the national population. The
methodology to estimate the numbers and proportions of thyroid
cancer cases attributable to overdiagnosis using population-level
data from cancer registries has been described elsewhere.2,4,8
Briefly, a growth of incidence with a power law of age was
consistently observed before the changes in diagnostic practice in
countries and registries where long-term data are available.5,8 This
“historical” age curve was then used to estimate the number of
incident cases that would have been expected if thyroid cancer
had continued to be detected primarily after symptoms or through
palpation (Appendix Figs. 2 and 3 in Supplemental Materials
found at https://doi.org/10.1016/j.jval.2023.02.016). We have
attributed to overdiagnosis the difference between the observed
and expected age-specific incidence and computed the proportion
of overdiagnosed cases over the total number of diagnosed thyroid
cancers.
Incidental Thyroid Cancer Cases and Treatment of
Overdiagnosed Patients
For 5 of 21 departments included in the FRANCIM network
(Isère, Bas-Rhin, Haut-Rhin, Deux-Sèvres, and Vienne) plus
another one (Rhone), we have also collected complementary in-
formation on the type of treatment according to the pathway and
modality of diagnosis. Based on this information, we estimated the
fraction of thyroid cancer cases that were incidentally discovered
and estimated the fraction of individuals who were treated
because they were overdiagnosed. There were 2 types of
 ECONOMIC EVALUATION 1177

Figure 1. Analysis of the patient management process of patients with thyroid cancer.

TSH indicates Thyroid stimulating hormone.

incidental discoveries. The first one consisted of cases that were Mean values of the estimates for the 6 departments (5 1 Rhone)
incidentally discovered after a thyroid surgery performed for pa- were applied to the remaining 16 departments.
thologies of the thyroid other than cancer: this group accounted
for 26.3% of all diagnosed cases, and because it could not be Total Costs of Thyroid Cancer Management and Share
considered to have been overtreated, it was entirely deducted Associated With Treatment of Overdiagnosed Cases
from the estimates of overdiagnosed cases. The second group
The total cost of thyroid cancer patient management was
consisted of incidental cases that were discovered while exam-
estimated by multiplying the mean cost per patient in 2012 to
ining a different nodule (which conversely turned out to be
2016 by the total number of cases treated for thyroid cancer
benign) and accounted for approximately 20% of all cases. Because
during 2011 to 2015, in each of the 21 departments (excluding
it is not possible to determine how many of these cases have been
those treated for other diseases of the thyroid and for whom
overdiagnosed (or not), we present 2 scenarios (Appendix Fig. 4 in
cancer was discovered incidentally). The corresponding share
Supplemental Materials found at https://doi.org/10.1016/j.jval.2
attributable to the treatment of overdiagnosed cases was done for
023.02.016): the first scenario assumes that none of the in-
the 2 scenarios. Extrapolation of these estimates to the whole
dividuals in this group were overdiagnosed and treated (lower
country was done by multiplying the total cost for 21 departments
bound) and the second scenario assumes that all the individuals in
by 4.4 given that these areas cover 22.7% of the total population in
this group were overdiagnosed and treated (upper bound). Thus,
France.
the final estimates were presented as a range of possible values for
the treatment of overdiagnosed cases and corresponding costs.
Department-specific estimates were used for the 5 departments Results
where the information on incidental discovery was available.
Mean Per Patient Costs
Study population
Between January 1, 2012, and December 31, 2016, 339 patients
Table 1. Sociodemographic characteristics of the EGB study were identified in the EGB database who had been diagnosed of
population (n = 313). thyroid cancer and underwent surgery. A total of 313 patients
were retained for the cost analysis after application of the exclu-
Characteristic n % sion criteria (Appendix Fig. 1 in Supplemental Materials found at
Age group, years https://doi.org/10.1016/j.jval.2023.02.016). Of these, 83% under-
18-44 105 33.5 went a total or subtotal thyroidectomy and 17% a partial thy-
45-64 141 45.0 roidectomy. The median age of patients was 51 years old and the
$ 65 67 21.4 majority were women (78%). Twenty-eight percent of thyroidec-
Sex (woman) 244 78.0 tomies took place at a university hospital, whereas the others in a
public or private nonuniversity hospital (Table 1).
Age, years, median (range) 51 66.0
Place of surgery Cost estimations
Nonuniversity hospital, public, or private 226 72.2 The utilization of healthcare resources and the associated costs
University hospital 87 27.8
for the 3 periods are presented in Table 2. The mean cost per
Thyroidectomy type capita of thyroid cancer management between 2012 and 2016
Total or subtotal 260 83.1 among 313 patients was V6248. It was higher for men (V7025)
Partial 53 16.9
than women (V6028) and decreased with increasing age, although
Year of surgery at faster pace for men than women (Appendix Table 1 in Sup-
2012 59 18.8 plemental Materials found at https://doi.org/10.1016/j.jval.2023.
2013 60 19.2 02.016). The operative period that represents the diagnosis-
2014 60 19.2
related group tariff for thyroid surgery was the largest contrib-
2015 65 20.8
2016 69 22.0
utor to total costs (57.4%). The postoperative or follow-up period
contributed also substantially (40.0% of to the total costs), with
EGB indicates Echantillon Généraliste des Bénéficiaires. radioactive iodine treatment being the most important contrib-
utor (25.6% of the total costs), which was administered to
1178 VALUE IN HEALTH AUGUST 2023

Table 2. Breakdown of costs (V) by operative period and activity between 2012 and 2016 (n = 313).

Activity Resource usage Total Expenditure

activities
Patients (across all
receiving at patients), N
least once
n* % (out of Total, V % (out of Mean, SD Median, Q1 Q3
313 patients)† the total V V
cost)§
Total 313 19 800 1 955 567 6248 2919 5941 4096 7471
Preoperative period (12 months 305 97.4 2883 51 463 2.6 169 137 140 94 209
before index)
Outpatient consultation 286 91.4 849 23 436 1.2 82 67 67 34 101
Biological analysis 288 92.0 1615 13 320 0.7 46 90 30 18 50
Cervical ultrasound 168 53.7 216 5437 0.3 32 14 26 25 37
FNAC 117 37.4 162 5064 0.3 43 26 27 27 54
Scintigraphy 39 12.5 41 4207 0.2 108 69 77 77 110
Perioperative period (index)
Inpatient stay‡ 313 100.0 313 1 122784 57.4 3587 1373 3672 2749 3740
Postoperative period 313 100.0 16 604 781 320 40.0 2523 2572 2342 296 3555
(24 months after index)
Outpatient consultation 301 96.2 1510 51 993 2.7 173 187 121 61 208
Biological analysis 309 98.7 4780 38 476 2.0 125 126 103 66 149
Cervical ultrasound 156 49.8 252 8337 0.4 53 36 36 35 71
FNAC 10 3.2 17 644 0.0 64 37 47 38 86
Scintigraphy 8 2.6 11 1386 0.1 173 97 110 110 290
Radioactive iodine treatment 170 54.3 214 500 380 25.6 2943 1265 2907 2071 3138
Secondary thyroidectomy 24 7.7 24 78 576 4.0 3274 761 3656 2478 3710
completion
Lymph node dissection 18 5.8 19 60 446 3.1 3358 1464 3475 2127 3723
Thyroid hormones 303 96.8 8309 17 474 0.9 58 24 54 43 73
Secondary hypoparathyroidism
Inpatient stay 4 1.3 6 14 401 0.7 3600 2189 3212 2093 5108
Prescriptions hypocalcemia 83 26.5 981 10 355 0.5 125 173 41 19 170
Recurrent laryngeal nerve palsy
Inpatient stay 5 1.6 7 16 701 0.9 3340 2359 3498 2071 3579
Speech therapist session 31 9.9 484 12 768 0.7 412 422 235 102 536
FNAC indicates fine needle aspiration cytology; Q, quartile.
*Number of patients receiving the services at least once.
†
Row percentage (of 313 individuals).
‡
Includes surgeon, anesthesia, and pathology fees.
§
Column percentage (of V1 955 567). Given that patients might have received multiple services, the costs of which may be available only in aggregation with others, costs
for specific items do not necessarily add up to the exact totals or subtotals.

approximately 54% of the patients. Complications, such as sec-
ondary hypoparathyroidism and/or recurrent laryngeal nerve
palsy, represented 2.3% of total costs.
Thyroid Cancer Management in 21 Departments
men, 10 846 were estimated to have been diagnosed of thyroid
cancer in France in 2011 to 2015, 6587 overdiagnosed, and 7885
treated in total, of whom between 1465 (in the first scenario) and
3626 (in the second scenario) treated because they were over-
diagnosed (Table 4).

Between 2011 and 2015, the 21 departments of the FRANCIM

network registered 7707 cases of thyroid cancer aged 15 to 84
years among women, of whom 5487 (71.2%) were estimated to
have been overdiagnosed. Among the total number of female
cases, 2095 cases were estimated to have been incidentally
discovered subsequently to the surgery of the thyroid for reasons
other than thyroid cancer. Thus, a total of 5612 women (7707 2
2095; representing 72.8% of all cases) were treated specifically for
thyroid cancer. Of these, between 1844 (24% of all diagnosed cases,
in the first scenario) and 3392 (44%, in the second scenario) were
estimated to have been treated because they were overdiagnosed.
The extrapolated nationwide figures for women were 33 911
diagnosed of thyroid cancer between 2011 and 2015, 24 143
overdiagnosed, 24 693 treated in total, and between 8114 and 14
925 treated because they were overdiagnosed (Table 3). Among
Total Costs for Thyroid Cancer Management and for
Treatment of Overdiagnosed Cases
When applying the mean costs for 2012 to 2016 to the
numbers obtained using FRANCIM for the period 2011 to 2015, we
estimated that the total cost of thyroid cancer patient manage-
ment in France was V203.5 million (V154.3 million for women
and V49.3 million for men), or V40.7 million per year. The total
cost attributable to treatment of overdiagnosed cases ranged be-
tween V59.9 million (V50.7 million for women and V9.2 million
for men; this corresponded to V12.0 million per year and to 29.4%
of the total cost) and V115.9 million (V93.3 million for women and
V22.7 million for men; this corresponded to V23.2 million per
year and to 56.9% of the total cost) (Tables 3 and 4).
 ECONOMIC EVALUATION 1179

Table 3. Summary table of the total number of thyroid cancer cases, of treatment of overdiagnosed cases, and relative associated
costs, among women, 2011 to 2015.

Department Total Overdiagnosed Incidental findings Treatment for cancer Costs for cancer
cases treatment
(million euros)
A B After While Total Overdiagnosed Total Overdiagnosed
surgery, examining (range) (range)
for reasons a distinct
other than nodule E= Lower Upper G= Lower Upper
cancer, C (subsequently A2C bound, bound, E 3 MCP* bound, bound,
benign), D E/A (%) F1 = B 2 F2 = H1 = F1 H2 = F2
C2D B2C 3 MCP* 3 MCP*
F1/A (%) F2/A (%) H1/G (%) H2/G (%)
21 departments 7707 5487 2095 1548 5612 (73) 1844 (24) 3392 (44) 35.1 11.5 (33) 21.2 (60)
France† 33 911 24 143 9218 6811 24 693 (73) 8114 (24) 14 925 (44) 154.3 50.7 (33) 93.3 (60)
By department
Ardennes 150 108 39 30 111 (74) 39 (26) 69 (46) 0.7 0.2 (35) 0.4 (62)
Calvados 283 189 74 56 209 (74) 59 (21) 115 (41) 1.3 0.4 (28) 0.7 (55)
Charente 144 100 38 29 106 (74) 33 (23) 62 (43) 0.7 0.2 (31) 0.4 (58)
Charente- 480 348 126 96 354 (74) 126 (26) 222 (46) 2.2 0.8 (36) 1.4 (63)
Maritime
Doubs 189 108 50 38 139 (74) 20 (11) 58 (31) 0.9 0.1 (14) 0.4 (42)
Gironde 1242 889 327 247 915 (74) 315 (25) 562 (45) 5.7 2.0 (34) 3.5 (61)
Hérault 425 343 112 85 313 (74) 146 (34) 231 (54) 2.0 0.9 (47) 1.4 (74)
Isère 1209 846 376 227 833 (69) 243 (20) 470 (39) 5.2 1.5 (29) 2.9 (56)
Loire- 604 439 159 120 445 (74) 160 (26) 280 (46) 2.8 1.0 (36) 1.7 (63)
Atlantique
Manche 146 94 38 29 108 (74) 27 (18) 56 (38) 0.7 0.2 (25) 0.3 (52)
Marne 328 222 86 65 242 (74) 71 (22) 136 (41) 1.5 0.4 (29) 0.8 (56)
Bas-Rhin 203 109 43 45 160 (79) 21 (10) 66 (33) 1.0 0.1 (13) 0.4 (41)
Haut-Rhin 210 129 86 8 124 (59) 35 (17) 43 (20) 0.8 0.2 (28) 0.3 (35)
Deux-Sèvres 393 293 83 150 310 (79) 60 (15) 210 (53) 1.9 0.4 (19) 1.3 (68)
Somme 269 202 71 54 198 (74) 77 (29) 131 (49) 1.2 0.5 (39) 0.8 (66)
Tarn 216 174 57 43 159 (74) 74 (34) 117 (54) 1.0 0.5 (47) 0.7 (74)
Vendée 451 323 119 90 332 (74) 114 (25) 204 (45) 2.1 0.7 (34) 1.3 (61)
Vienne 197 164 62 23 135 (69) 79 (40) 102 (52) 0.8 0.5 (59) 0.6 (76)
Haute-Vienne 216 157 57 43 159 (74) 57 (26) 100 (46) 1.0 0.4 (36) 0.6 (63)
Territoire 43 39 11 9 32 (74) 19 (44) 28 (65) 0.2 0.1 (59) 0.2 (88)
de Belfort
Lille Métropole 309 211 81 61 228 (74) 69 (22) 130 (42) 1.4 0.4 (30) 0.8 (57)
MCP indicates mean cost per patient.
*MCP, which equals to V6248.
†
Extrapolated to the whole France. The 21 departments covered 22.7% of the total population in France, so the number of cases and associated costs were multiplied by
4.4.

Discussion
This retrospective study shows that the estimated cost of thyroid
cancer management in France in 2011 to 2015 was . V200 million,
of which between 29% and 57% could be potentially avoidable
because it was attributable to the treatment of overdiagnosed
cancers. Information from multiple sources of data—from cancer
registry data and from healthcare insurance—was integrated with a
previously developed epidemiological methodology that quantifies
overdiagnosis of thyroid cancer at the population level.
On average, the French health system spent . V6200 for a
patient with thyroid cancer in that period, with the most impor-
tant components being the inpatient stay, which includes surgery
and contributes to . 50% of the total costs, and radioactive
treatment. The average cost per capita for thyroid cancer man-
agement obtained in this study was larger than that reported for
France by Finnerty et al,14 that is, US $4600 in 2009 to 2013, likely
because this referred to an earlier period and considered post-
operative costs only within 1 year (instead of 2 years, as in the
present study). Most of the studies on expenditures for thyroid
management have been conducted in the United States, where the
costs are approximately 3 times those in France.14 Compared with
the management of other cancers, the per capita cost of thyroid
cancer is generally lower,20 although the total costs are quite large
in absolute terms. In the United States, Lubitz et al17 found that the
total amount spent for thyroid cancer was comparable with that
spent for other solid tumors, such as cervical, gastric, and
esophageal cancer. Similarly in France, the V200 million estimated
in our study for thyroid cancer management over 5 years was
lower than the total costs for management of other frequent
cancers, such as cancer of the breast, colorectum, lung, and
prostate,26 but comparable with those for cervical cancer.27
This study has several limitations. The economic costs were
derived from the EGB database, which covers only a relatively
small proportion of the insured individuals in France, but is
based on a representative sample of the population, and there-
fore allows to reliably estimate the average costs for thyroid
cancer management and to follow all healthcare consumptions.
Indeed, our estimates for the costs of thyroidectomy of cancer
and impatient stay (approximately V3600) are similar to those
reported by a national study for year 2010 that have used the
Système National d’Information Inter Régimes de l’Assurance
Maladie database and that have included 77% of the whole
French population.28 It is also worth noting that the present
study is limited to the direct costs from the perspective of the
health insurance, not the societal costs, and does not take into
1180 VALUE IN HEALTH AUGUST 2023

Table 4. Summary table of the total number of thyroid cancer cases, of treatment of overdiagnosed cases, and relative associated
costs, among men, 2011 to 2015.

Department Total Overdiagnosed Incidental Treatment for cancer Costs for

cases findings cancer treatment
(million euros)
A B After While Total Overdiagnosed Total Overdiagnosed
surgery, examining (range) (range)
for reasons a distinct
other than nodule E= Lower Upper G= Lower Upper
cancer, C (subsequently A2C bound, bound, E 3 bound, bound,
benign), D E/A (%) F1 = F2 = MCP* H1 H2 =
B2 B2C = F1 3 F2 3
C2D F2/A (%) MCP* MCP*
F1/A (%) H1/G (%) H2/G (%)
21 2465 1497 673 491 1792 (73) 333 (14) 824 (33) 11.2 2.08 (19) 5.15 (46)
departments
France† 10 846 6587 2961 2160 7885 (73) 1465 (14) 3626 (33) 49.3 9.15 (19) 22.65 (46)
By department
Ardennes 53 43 14 11 39 (74) 18 (34) 29 (55) 0.2 0.11 (46) 0.18 (74)
Calvados 82 62 22 16 60 (73) 24 (29) 40 (49) 0.4 0.15 (40) 0.25 (67)
Charente 53 19 14 11 39 (74) 0 (0)‡ 5 (9) 0.2 0 (0) 0.03 (13)
Charente- 149 87 39 30 110 (74) 18 (12) 48 (32) 0.7 0.11 (16) 0.30 (44)
Maritime
Doubs 66 22 17 13 49 (74) 0 (0)‡ 5 (8) 0.3 0 (0) 0.03 (10)
Gironde 411 290 108 82 303 (74) 100 (24) 182 (44) 1.9 0.62 (33) 1.14 (60)
Hérault 125 79 33 25 92 (74) 21 (17) 46 (37) 0.6 0.13 (23) 0.29 (50)
Isère 350 219 109 66 241 (69) 44 (13) 110 (31) 1.5 0.27 (18) 0.69 (46)
Loire- 199 110 52 40 147 (74) 18 (9) 58 (29) 0.9 0.11 (12) 0.36 (39)
Atlantique
Manche 40 15 11 8 29 (73) 0 (0)‡ 4 (10) 0.2 0 (0) 0.02 (14)
Marne 99 67 26 20 73 (74) 21 (21) 41 (41) 0.5 0.13 (29) 0.26 (56)
Bas-Rhin 62 35 13 14 49 (79) 8 (13) 22 (35) 0.3 0.05 (16) 0.14 (45)
Haut-Rhin 91 45 37 3 54 (59) 5 (5) 8 (9) 0.3 0.03 (9) 0.05 (15)
Deux-Sèvres 119 76 25 45 94 (79) 6 (5) 51 (43) 0.6 0.04 (6) 0.32 (54)
Somme 71 56 19 14 52 (73) 23 (32) 37 (52) 0.3 0.14 (44) 0.23 (71)
Tarn 67 43 18 13 49 (73) 12 (18) 25 (37) 0.3 0.07 (24) 0.16 (51)
Vendée 141 84 37 28 104 (74) 19 (13) 47 (33) 0.6 0.12 (18) 0.29 (45)
Vienne 66 31 21 8 45 (68) 2 (3) 10 (15) 0.3 0.01 (4) 0.06 (22)
Haute-Vienne 96 41 25 19 71 (74) 0 (0)‡ 16 (17) 0.4 0 (0) 0.10 (23)
Territoire 14 4 4 3 10 (71) 0 (0)‡ 0 (0) 0.1 0 (0) 0 (0)
de Belfort
Lille Métropole 111 69 29 22 82 (74) 18 (16) 40 (36) 0.5 0.11 (22) 0.25 (49)

MCP indicates mean cost per patient.

*MCP, which equals to V6248.
†
Extrapolated to the whole France. The 21 departments covered 22.7% of the total population in France, so the number of cases and associated costs were multiplied by
4.4.
‡
Negative values were constrained to be 0.

account the quality-of-life impact due to unnecessary surgery
and maintenance treatment to hypoparathyroidism. Important
economic components to consider would also be direct
nonmedical costs (such as time spent by patients receiving
medical care) and lost productivity of patients and caregivers. In
addition, the analysis did not include indirect costs related to
sick leave paid for patients, which may constitute an additional
and large source of costs: Mathonnet et al29 found that “The
mean duration of sick leave for employed patients was 89 days
for patients with thyroid cancer and 38 days for patients with
benign nodules. Sick leave lasted more than 3 weeks in 60–81%
of cases, depending on the group.” Moreover, other indirect costs
have been described, such as income or job loss and difficulties
to obtain a loan or mortgage, a problem that motivated France to
introduce the “right to be forgotten” in 2014,21 which allows
certain categories of cancer survivors, including thyroid cancer
survivors, to be able not to disclose their history of cancer a
certain period after treatment. In this sense, our estimations on
the socioeconomic burden due to overdiagnosis are largely
conservative, especially on account of the relatively young age at
diagnosis. Another possible limitation is the use of a study design
focused on the costs at treatment. Other studies have focused on
all phases of care, including the last year of life, and this may
have the advantage of including all costs in the care of patients.20
Thus, the 2 years of follow-up for each individual is considered to
be largely sufficient to capture most of the costs, although the
lifelong treatment levothyroxine necessary to most patients may
lead to slightly conservative cost estimations. The total number
of individuals diagnosed of thyroid cancer has increased rapidly
in the past decades, and at least up until where the most recent
data allow to observe, it is still rising in many departments of
France.2 Therefore, although the extrapolation of the costs
derived from 21 departments to the whole of France is inevitably
an approximation, given the large departmental variability in the
incidence rates of the disease, the overall expenditure for the
disease will likely continue to increase in the near future. Given
that a large fraction of thyroid cancer cases are overdiagnosed,
there is a large potential for avoiding or, at least, substantially
reducing these expenses. Unfortunately, the estimation of over-
diagnosis (and the costs associated with overtreatment) in the

present study can be done only at the population level, and
therefore, it is not possible to know whether a specific patient
has been overdiagnosed. Nevertheless, epidemiological methods
can estimate overdiagnosis at the population level and together
with other sources of data (eg, nationwide insurance database,
cancer registry, and medical records) may help clarifying several
important steps in the care pathway that lead to diagnosis,
overdiagnosis and treatment, and consequently their economic
costs nationally.
In the present study, the information collected showed that
the fraction of thyroid cancers incidentally discovered during
thyroidectomy for benign disease amounted to approximately
one-fourth of all cases diagnosed: this allowed to obtain the
number of cases specifically treated for thyroid cancer by sub-
tracting them from the total cases. Furthermore, another rele-
vant fraction (approximately one-fifth) of the total number of
diagnosed cancers was attributable to incidental findings of
cancers that occurred while performing a histological exami-
nation of a distinct nodule. As opposed to the previous case,
this type of incidental finding is of relevance for the manage-
ment of thyroid cancer. Nevertheless, because we could not
reliably estimate and assign a specific value to the fraction of
overdiagnosed in this group of patients, we have therefore
proposed a range of values lying between the 2 most extreme
scenarios.
Reassuringly, the incidence of thyroid cancer, and likely the
number of overdiagnosed cases, has started to stabilize or decline in
some departments of France—although only among women1,2—
which may lead to some future cost reductions in the management
of thyroid cancer. An additional factor that may reduce costs in this
area is that since 2015 there has been a de-escalating strategy with
a more conservative attitude to limit unnecessary aggressive
treatments, for example, by providing indication for radioiodine
ablation according to the pathological characteristics of the tumor
and by replacing to a certain degree total, with partial,
thyroidectomy.30
Conclusion
In conclusion, the management of thyroid cancer represents
not only a relevant clinical and public health problem but also a
potentially important economic burden. Given that between V60
and V116 million—of a total expense of V204 million—has been
estimated to be associated with the treatment of overdiagnosed
thyroid cancer cases in France in only 5 years, other clinical studies
are needed to complete this epidemiological information and to
better appreciate the phenomenon. Although it is not always clear
how to achieve a reduction of overdiagnosis of thyroid cancer, of
the burden that overtreatment puts on the patients in terms of
their health and of the economic costs associated with over-
treatment (eg, ensuring adherence to the guidelines that recom-
mend against screening of the thyroid for asymptomatic people,
adherence to the more conservative approaches in the treatment
and management of thyroid cancer, by improving risk stratifica-
tion),31 it is imperative to continue monitoring and quantifying
the phenomenon of thyroid cancer overdiagnosis and the relative
associated costs.
Supplemental Material
Supplementary data associated with this article can be found in the
online version at https://doi.org/10.1016/j.jval.2023.02.016.
ECONOMIC EVALUATION 1181
Article and Author Information
Accepted for Publication: February 27, 2023
Published Online: April 5, 2023
doi: https://doi.org/10.1016/j.jval.2023.02.016
Author Affiliations: Cancer Surveillance Branch, International Agency
for Research on Cancer, Lyon, France (Li, Meheus, Simon, Combes,
Vaccarella); Department of Cancer Prevention, State Key Laboratory of
Oncology in South China, Collaborative Innovation Center for Cancer
Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China (Li);
Department of Health Systems Governance and Financing, World Health
Organization, Geneva, Switzerland (Meheus); Research on Healthcare
Performance (RESHAPE), INSERM U1290, Université Claude Bernard Lyon
1, Lyon, France (Polazzi, Borson-Chazot, Duclos); Health Data
Department, Hospices Civils de Lyon, Lyon, France (Polazzi, Duclos);
Registre du cancer de l’Isère, Grenoble, France (Delafosse, Seigneurin,
Colonna); Fédération d’Endocrinologie, Groupement Hospitalier Est and
Registre des Cancers Thyroïdiens du Rhône, Hospices Civils de Lyon,
Lyon, France (Borson-Chazot); Cancer Epidemiology Unit, Centro di
Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a
Carattere Scientifico, Aviano, Italy (Dal Maso).
Correspondence: Salvatore Vaccarella, PhD, International Agency for
Research on Cancer, 150 Cours Albert Thomas 69372, Lyon Cedex 08,
France. Email: vaccarellas@iarc.fr
Author Contributions: Concept and design: Li, Meheus, Delafosse,
Colonna, Vaccarella
Acquisition of data: Polazzi, Delafosse, Duclos
Analysis and interpretation of data: Li, Meheus, Polazzi, Delafosse,
Borson-Chazot, Dal Maso, Duclos, Vaccarella
Drafting of the manuscript: Li, Meheus, Dal Maso, Vaccarella
Critical revision of the paper for important intellectual content: Li, Meheus,
Polazzi, Delafosse, Borson-Chazot, Seigneurin, Combes, Dal Maso,
Colonna, Duclos, Vaccarella
Statistical analysis: Li, Polazzi, Duclos, Vaccarella
Provision of study materials or patients: Delafosse
Obtaining funding: Vaccarella, Colonna, Administrative, technical, or logistic
support: Delafosse, Simon, Combes, Vaccarella
Supervision: Vaccarella
Conflict of Interest Disclosures: The authors reported no conflicts of
interest. Where authors are identified as personnel of the International
Agency for Research on Cancer/World Health Organization, the authors
alone are responsible for the views expressed in this article and they do
not necessarily represent the decisions, policy, or views of the
International Agency for Research on Cancer/World Health Organization.
Funding/Support: This study was funded by French Institut National du
Cancer (INCa) (grant number 2017-138) and by the Italian Association for
Cancer Research (AIRC) (Grant no. 21879).
Role of the Funder/Sponsor: The funder had no role in the design and
conduct of the study; collection, management, analysis, and
interpretation of the data; preparation, review, or approval of the
manuscript; and decision to submit the manuscript for publication.
Acknowledgment: The authors thank all those who contributed to the
recording of cancer data in the registries, most particularly the
laboratories and departments of pathological anatomy and cytology, the
departments of medical information of public and private hospitals, the
local offices of Assurance Maladie, and all general practitioners and
specialists.
Ethics Statement: This study was strictly observational and based on
anonymous data. Therefore, in accordance with the French ethical
directives, it did not require a written informed consent from the
participants or the authorization from an ethic committee. The Hospices
Civils de Lyon, as a health research institute, has been authorized to use
the EGB database by the French data protection authority (Commission
Nationale de l’Informatique et des Libertés), provided that the researcher
follows specific training with certification and records his/her study into
the register of EGB studies performed in the institute.
1182 VALUE IN HEALTH
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