Background: Medullary thyroid carcinoma (MTC) is rare. Nationwide population-based studies are important to evaluate its clinical course. Objectives: To describe all patients with MTC in Norway during 1994–2016 and compare time-related trends in diagnostics and surgical treatment, including prognostic factors for biochemical cure and disease-specific survival (DSS). Methods: This retrospective population-based cohort study includes data for 228 out of 237 patients (96%) with MTC; 201 patients were surgically treated. Patients were identified in the 4 regional centers treating MTC and by the Cancer Registry of Norway. Data were collected from patients’ files. Trends were compared over 2 study periods. Results: MTC accounted for 4.2% of thyroid carcinomas. During the study periods, the incidence increased from 0.18 to 0.25: 100,000 per year, preoperative diagnostics improved with increased use of calcitonin, ultrasound, and fine-needle cytology (p = 0.010, p < 0,001, and p = 0.001), patients were diagnosed at an earlier tumor stage (p = 0.004), and more patients were cured (p = 0.002). Via multivariate analysis of patients with metastatic lymph nodes, independent prognostic factors for cure were: a low ratio of metastatic and total number of dissected lymph nodes (p = 0.021) and no extrathyroidal extension (p = 0.030). Independent prognostic factors for DSS were: no distant metastasis, a younger age, and a low ratio of metastatic and dissected lymph nodes (p = 0.005, p = 0.020, p = 0.022). Conclusions: Preoperative diagnostics have improved over time with increased therapeutic control. A low ratio of metastatic and dissected lymph nodes predicts better outcomes in patients with metastatic lymph nodes.

1.
Kebebew
E
,
Ituarte
PH
,
Siperstein
AE
,
Duh
QY
,
Clark
OH
.
Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems
.
Cancer
.
2000
Mar
;
88
(
5
):
1139
48
.
[PubMed]
0008-543X
2.
Akslen
LA
,
Haldorsen
T
,
Thoresen
SO
,
Glattre
E
.
Incidence of thyroid cancer in Norway 1970-1985. Population review on time trend, sex, age, histological type and tumour stage in 2625 cases
.
APMIS
.
1990
Jun
;
98
(
6
):
549
58
.
[PubMed]
1600-0463
3.
Wells
SA
 Jr
,
Asa
SL
,
Dralle
H
,
Elisei
R
,
Evans
DB
,
Gagel
RF
, et al.;
American Thyroid Association Guidelines Task Force on Medullary Thyroid Carcinoma
.
Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma
.
Thyroid
.
2015
Jun
;
25
(
6
):
567
610
.
[PubMed]
1050-7256
4.
Pelizzo
MR
,
Boschin
IM
,
Bernante
P
,
Toniato
A
,
Piotto
A
,
Pagetta
C
, et al.
Natural history, diagnosis, treatment and outcome of medullary thyroid cancer: 37 years experience on 157 patients
.
Eur J Surg Oncol
.
2007
May
;
33
(
4
):
493
7
.
[PubMed]
0748-7983
5.
Donis-Keller
H
,
Dou
S
,
Chi
D
,
Carlson
KM
,
Toshima
K
,
Lairmore
TC
, et al.
Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC
.
Hum Mol Genet
.
1993
Jul
;
2
(
7
):
851
6
.
[PubMed]
0964-6906
6.
Mulligan
LM
,
Kwok
JB
,
Healey
CS
,
Elsdon
MJ
,
Eng
C
,
Gardner
E
, et al.
Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A
.
Nature
.
1993
Jun
;
363
(
6428
):
458
60
.
[PubMed]
0028-0836
7.
Eng
C
,
Smith
DP
,
Mulligan
LM
,
Nagai
MA
,
Healey
CS
,
Ponder
MA
, et al.
Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours
.
Hum Mol Genet
.
1994
Feb
;
3
(
2
):
237
41
.
[PubMed]
0964-6906
8.
Romei
C
,
Cosci
B
,
Renzini
G
,
Bottici
V
,
Molinaro
E
,
Agate
L
, et al.
RET genetic screening of sporadic medullary thyroid cancer (MTC) allows the preclinical diagnosis of unsuspected gene carriers and the identification of a relevant percentage of hidden familial MTC (FMTC)
.
Clin Endocrinol (Oxf)
.
2011
Feb
;
74
(
2
):
241
7
.
[PubMed]
0300-0664
9.
de Groot
JW
,
Plukker
JT
,
Wolffenbuttel
BH
,
Wiggers
T
,
Sluiter
WJ
,
Links
TP
.
Determinants of life expectancy in medullary thyroid cancer: age does not matter
.
Clin Endocrinol (Oxf)
.
2006
Dec
;
65
(
6
):
729
36
.
[PubMed]
0300-0664
10.
Gatta
G
,
Ciccolallo
L
,
Kunkler
I
,
Capocaccia
R
,
Berrino
F
,
Coleman
MP
, et al.;
EUROCARE Working Group
.
Survival from rare cancer in adults: a population-based study
.
Lancet Oncol
.
2006
Feb
;
7
(
2
):
132
40
.
[PubMed]
1470-2045
11.
Modigliani
E
,
Cohen
R
,
Campos
JM
,
Conte-Devolx
B
,
Maes
B
,
Boneu
A
, et al.
Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d’étude des tumeurs à calcitonine
.
Clin Endocrinol (Oxf)
.
1998
Mar
;
48
(
3
):
265
73
.
[PubMed]
0300-0664
12.
Torresan
F
,
Cavedon
E
,
Mian
C
,
Iacobone
M
.
Long-Term Outcome After Surgery for Medullary Thyroid Carcinoma: A Single-Center Experience
.
World J Surg
.
2018
Feb
;
42
(
2
):
367
75
.
[PubMed]
0364-2313
13.
Randle
RW
,
Balentine
CJ
,
Leverson
GE
,
Havlena
JA
,
Sippel
RS
,
Schneider
DF
, et al.
Trends in the presentation, treatment, and survival of patients with medullary thyroid cancer over the past 30 years
.
Surgery
.
2017
Jan
;
161
(
1
):
137
46
.
[PubMed]
0039-6060
14.
Machens
A
,
Dralle
H
.
Breach of the thyroid capsule and lymph node capsule in node-positive papillary and medullary thyroid cancer: different biology
.
Eur J Surg Oncol
.
2015
Jun
;
41
(
6
):
766
72
.
[PubMed]
0748-7983
15.
Roman
S
,
Lin
R
,
Sosa
JA
.
Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases
.
Cancer
.
2006
Nov
;
107
(
9
):
2134
42
.
[PubMed]
0008-543X
16.
Machens
A
,
Dralle
H
.
Biomarker-based risk stratification for previously untreated medullary thyroid cancer
.
J Clin Endocrinol Metab
.
2010
Jun
;
95
(
6
):
2655
63
.
[PubMed]
0021-972X
17.
Dralle
H
,
Machens
A
.
Surgical management of the lateral neck compartment for metastatic thyroid cancer
.
Curr Opin Oncol
.
2013
Jan
;
25
(
1
):
20
6
.
[PubMed]
1040-8746
18.
Brauckhoff
M
,
Machens
A
,
Lorenz
K
,
Bjøro
T
,
Varhaug
JE
,
Dralle
H
.
Surgical curability of medullary thyroid cancer in multiple endocrine neoplasia 2B: a changing perspective
.
Ann Surg
.
2014
Apr
;
259
(
4
):
800
6
.
[PubMed]
0003-4932
19.
Opsahl
EM
,
Brauckhoff
M
,
Schlichting
E
,
Helset
K
,
Svartberg
J
,
Brauckhoff
K
, et al.
A Nationwide Study of Multiple Endocrine Neoplasia Type 2A in Norway: Predictive and Prognostic Factors for the Clinical Course of Medullary Thyroid Carcinoma
.
Thyroid
.
2016
Sep
;
26
(
9
):
1225
38
.
[PubMed]
1050-7256
20.
Edge
SB
,
Byrd
DR
,
Compton
CC
,
Fritz
AG
,
Greene
FL
,
Trotti
A
, editors
.
AJCC Cancer Staging Manual
. 7th ed.
New York (NY)
:
Springer-Verlag
;
2010
.
21.
Cancer Registry of Norway
. Available at: www.kreftregisteret.no. Accessed January 31, 2018.
22.
Statistic Norway
. Available at: www.ssb.no. Accessed April 25, 2017.
23.
Elisei
R
,
Bottici
V
,
Luchetti
F
,
Di Coscio
G
,
Romei
C
,
Grasso
L
, et al.
Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders
.
J Clin Endocrinol Metab
.
2004
Jan
;
89
(
1
):
163
8
.
[PubMed]
0021-972X
24.
Costante
G
,
Meringolo
D
,
Durante
C
,
Bianchi
D
,
Nocera
M
,
Tumino
S
, et al.
Predictive value of serum calcitonin levels for preoperative diagnosis of medullary thyroid carcinoma in a cohort of 5817 consecutive patients with thyroid nodules
.
J Clin Endocrinol Metab
.
2007
Feb
;
92
(
2
):
450
5
.
[PubMed]
0021-972X
25.
Cheung
K
,
Roman
SA
,
Wang
TS
,
Walker
HD
,
Sosa
JA
.
Calcitonin measurement in the evaluation of thyroid nodules in the United States: a cost-effectiveness and decision analysis
.
J Clin Endocrinol Metab
.
2008
Jun
;
93
(
6
):
2173
80
.
[PubMed]
0021-972X
26.
National Guidelines in Norway 29th of June
2017
(In Norwegian). Available at www.Helsedirektoratet.no. Accessed August 23, 2018.
27.
Dralle
H
,
Damm
I
,
Scheumann
GF
,
Kotzerke
J
,
Kupsch
E
,
Geerlings
H
, et al.
Compartment-oriented microdissection of regional lymph nodes in medullary thyroid carcinoma
.
Surg Today
.
1994
;
24
(
2
):
112
21
.
[PubMed]
0941-1291
28.
Moley
JF
,
Wells
SA
,
Dilley
WG
,
Tisell
LE
.
Reoperation for recurrent or persistent medullary thyroid cancer
.
Surgery
.
1993
Dec
;
114
(
6
):
1090
5
.
[PubMed]
0039-6060
29.
Tisell
LE
,
Hansson
G
,
Jansson
S
,
Salander
H
.
Reoperation in the treatment of asymptomatic metastasizing medullary thyroid carcinoma
.
Surgery
.
1986
Jan
;
99
(
1
):
60
6
.
[PubMed]
0039-6060
30.
Qu
N
,
Shi
RL
,
Lu
ZW
,
Liao
T
,
Wen
D
,
Sun
GH
, et al.
Metastatic lymph node ratio can further stratify risk for mortality in medullary thyroid cancer patients: A population-based analysis
.
Oncotarget
.
2016
Oct
;
7
(
40
):
65937
45
.
[PubMed]
1949-2553
31.
Leggett
MD
,
Chen
SL
,
Schneider
PD
,
Martinez
SR
.
Prognostic value of lymph node yield and metastatic lymph node ratio in medullary thyroid carcinoma
.
Ann Surg Oncol
.
2008
Sep
;
15
(
9
):
2493
9
.
[PubMed]
1068-9265
32.
Hirsch
D
,
Twito
O
,
Levy
S
,
Bachar
G
,
Robenshtok
E
,
Gross
DJ
, et al.
Temporal Trends in the Presentation, Treatment, and Outcome of Medullary Thyroid Carcinoma: An Israeli Multicenter Study
.
Thyroid
.
2018
Mar
;
28
(
3
):
369
76
.
[PubMed]
1050-7256
33.
Kazaure
HS
,
Roman
SA
,
Sosa
JA
.
Medullary thyroid microcarcinoma: a population-level analysis of 310 patients
.
Cancer
.
2012
Feb
;
118
(
3
):
620
7
.
[PubMed]
0008-543X
34.
Machens
A
,
Dralle
H
.
Surgical cure rates of sporadic medullary thyroid cancer in the era of calcitonin screening
.
Eur J Endocrinol
.
2016
Sep
;
175
(
3
):
219
28
.
[PubMed]
0804-4643
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.