GENERAL ICD- C73: Thyroid cancer Page 2 of 15 ICD- C73: Malignant neoplasm of thyroid gland Period of diagnosis % Relative survival N=7,95 9

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1 Munich Cancer Registry Incidence and Mortality Selection Matrix Homepage Deutsch ICD- C73: Thyroid cancer Survival Year of diagnosis Patients 953 7,13 Diseases 957 7,18 Cases evaluated 878 6,274 Creation date 8/22/217 Export date 8/16/217 Population 4.81 m BERLIN GERMANY BAVARIA MUNICH Munich Cancer Registry at Munich Cancer Center Marchioninistr. 15 Munich, Germany E-ICD--C73-Thyroid-cancersurvival.pdf

2 GENERAL ICD- C73: Thyroid cancer Page 2 of 15 ICD- C73: Malignant neoplasm of thyroid gland Period of diagnosis % Relative survival N=7, Figure 1a. Relative survival of patients with thyroid cancer by period of diagnosis. Included in the evaluation are 7,95 cases diagnosed between 1988 and 215. The survival results of the SEER program (Surveillance, Epidemiology, and End Results) of the American National Cancer Institute (NCI) are summarized as the period of diagnosis from 2 to 214, and are represented by colored diamonds in order to facilitate comparisons between MCR and SEER. The presented survival curves are derived from clinical records with valid follow-up informations, which means that death certificate cases (DCO) cases are omitted from the analysis. With this one restriction, the MCR has provided populationbased statistics since 1998, collecting data on all cancer cases in the region of southern Bavaria. Historical data of previous time periods can be heavily selected, therefore, univariate survival comparisons of the presented time periods must be carefully considered. Nonetheless, all calculable survival curves are depicted to facilitate the comparison of long time follow-up analyses of relative survival between particular cancers. Period of diagnosis n=877 n=2,296 n=3,922 obs. % rel. % obs. % rel. % obs. % rel. % Table 1b. Observed (obs.) and relative (rel.) survival of patients with thyroid cancer by period of diagnosis for period (N=7,95). Period of diagnosis n= % n=2, % 27+ n=3, % SEER n=3,61

3 GENERAL ICD- C73: Thyroid cancer Page 3 of 15 ICD- C73: Malignant neoplasm of thyroid gland Gender % Survival N=6,218 N=6218 Gender 9 8 Male n=1, % Female n=4, % Observed Expected Relative Figure 2a. Survival of patients with thyroid cancer by gender. Included in the evaluation are 6,218 cases diagnosed between 1998 and 215. Gender Male Female n=1,695 n=4,523 obs. % rel. % obs. % rel. % Table 2b. Observed (obs.) and relative (rel.) survival of patients with thyroid cancer by gender for period (N=6,218).

4 GENERAL ICD- C73: Thyroid cancer Page 4 of 15 ICD- C73: Malignant neoplasm of thyroid gland Age category % Relative survival N=7, Figure 3a. Relative survival of patients with thyroid cancer by age category. Included in the evaluation are 7,95 cases diagnosed between 1988 and 215. Age category -49 yrs 5-59 yrs 6-69 yrs 7+ yrs n=3,196 n=1,663 n=1,33 n=96 obs. % rel. % obs. % rel. % obs. % rel. % obs. % rel. % Table 3b. Observed (obs.) and relative (rel.) survival of patients with thyroid cancer by age category for period (N=7,95). Age category -49 yrs n=3, % 5-59 yrs n=1, % 6-69 yrs n=1, % 7+ yrs n= %

5 GENERAL ICD- C73: Thyroid cancer Page 5 of 15 ICD- C73: Malignant neoplasm of thyroid gland Histology % Relative survival N=7,3 1 Histology NOS n= % Follicular n= % Papillary n=5, % Medullary n=39 4.4% Anaplastic n=28 3.% NA n=65.9% Figure 4a. Relative survival of patients with thyroid cancer by histology. For 7,3 of 7,95 cases diagnosed between 1988 and 215 valid data could be obtained for this item. The grey line represents the subgroup of 65 patients with missing values regarding histology (.9 % of 7,95 patients, the percent values of all other categories are related to n=7,3). Histology NOS Follicular Papillary Medullary Anaplastic NA n=317 n=87 n=5,389 n=39 n=28 n=65 obs. % rel. % obs. % rel. % obs. % rel. % obs. % rel. % obs. % rel. % obs. % rel. % Table 4b. Observed (obs.) and relative (rel.) survival of patients with thyroid cancer by histology for period (N=7,3).

6 GENERAL ICD- C73: Thyroid cancer Page 6 of 15 ICD- C73: Malignant neoplasm of thyroid gland % Relative survival N=2, T1 n=1, % T2 n= % T3+4 n= % N n=1, % N+ n= % NX n=46 2.6% M1 n= % NA/NOS n=67 3.% Figure 4c. Relative survival of patients with thyroid cancer by. For 2,232 of 2,296 cases diagnosed between 1998 and 26 valid data could be obtained for this item. For a total of 2,229 cases an evaluable classification was established. The accumulated percentage exceeds the % value because patients are potientially considered in more than one subgroup. The grey line represents the subgroup of 67 patients with missing values regarding (2.9 % of 2,296 patients, the percent values of all other categories are related to n=2,229). Due to substantial changes in stage classification schemes long-term survival statistics over decades could not be created. T1 T2 T3+4 N N+ NX M1 n=1,162 n=421 n=614 n=1,186 n=394 n=46 n=114 obs. % rel. % obs. % rel. % obs. % rel. % obs. % rel. % obs. % rel. % obs. % rel. % obs. % rel. %

7 GENERAL ICD- C73: Thyroid cancer Page 7 of 15 cont'd NA/NOS n=67 obs. % rel. % Table 4d. Observed (obs.) and relative (rel.) survival of patients with thyroid cancer by TNM staging for period (N=2,229).

8 GENERAL ICD- C73: Thyroid cancer Page 8 of 15 ICD- C73: Malignant neoplasm of thyroid gland % Relative survival N=3, T1 n=2, % T2 n= % T3+4 n= % N n=1, % N+ n= % NX n=1, % M1 n= % NA/NOS n=7 1.8% Figure 4e. Relative survival of patients with thyroid cancer by. For 3,855 of 3,922 cases diagnosed between 27 and 215 valid data could be obtained for this item. For a total of 3,852 cases an evaluable classification was established. The accumulated percentage exceeds the % value because patients are potientially considered in more than one subgroup. The grey line represents the subgroup of 7 patients with missing values regarding (1.8 % of 3,922 patients, the percent values of all other categories are related to n=3,852). Due to substantial changes in stage classification schemes long-term survival statistics over decades could not be created. T1 T2 T3+4 N N+ NX M1 n=2,461 n=465 n=876 n=1,652 n=689 n=1,147 n=142 obs. % rel. % obs. % rel. % obs. % rel. % obs. % rel. % obs. % rel. % obs. % rel. % obs. % rel. % cont'd NA/NOS n=7 obs. % rel. % Table 4f. Observed (obs.) and relative (rel.) survival of patients with thyroid cancer by for period (N=3,852).

9 GENERAL ICD- C73: Thyroid cancer Page 9 of 15 ICD- C73: Malignant neoplasm of thyroid gland Extent of disease % Conditional relative 5 year survival N=6, Extent of disease Local n=5, % Regional n=1, % Distant n= % 7 NA/NOS n= % Time since diagnosis (years) Figure 4g. Conditional relative 5-year survival of patients with thyroid cancer by extent of disease. For 6,98 of 7,95 cases diagnosed between 1988 and 215 valid data could be obtained for this item. For a total of 6,899 cases an evaluable classification was established. The grey line represents the subgroup of 196 patients with missing values regarding extent of disease (2.8 % of 7,95 patients, the percent values of all other categories are related to n=6,899). Extent of disease Local Regional Distant NA/NOS Cond. Cond. Cond. Cond. surv. % surv. % surv. % surv. % n 5 yrs n 5 yrs n 5 yrs n 5 yrs 5, , , , , , , , , , , , Table 4h. Conditional relative 5-year survival of patients with thyroid cancer by extent of disease for period (N=6,899). Conditional relative survival rates refer to the relative survival probability, in this case for 5 years after cancer diagnosis, compared to the age- and sex-matched population (= %) under the condition of being alive for a certain time period (x-axis in Figure 4e). The results illustrate to what extent the cancer induced mortality of particular subgroups declines in the subsequent years after detection of the malignancy. For instance, according to the presented survival statistics, patients in the subgroup extent of disease= Local, who are alive at least 3 years after cancer diagnosis, the conditional relative 5-year survival rate is.% (n=4,182).

10 PROGRESSION ICD- C73: Thyroid cancer Page of 15 % Time to first progression (TTP) N=5, Type of progression Any type (CI) Events=421 Any type (1-KM) Events=421 Local relapse (CI) Events=87 Local relapse (1-KM) Events=87 Lymph node (CI) Events=135 Lymph node (1-KM) Events=135 Distant metastasis (CI) Events=223 Distant metast. (1-KM) Events=223 NOS (CI) Events=36 NOS (1-KM) Events=36 Figure 5a. Time to first progression of 5,882 patients with thyroid cancer diagnosed between 1998 and 215 (in solid cancers M only) estimated by cumulative incidence function (CI, solid line) accounting for death as competing risk and by inverse Kaplan-Meier estimate (1-KM, dashed line). The frequency of events may be underestimated due to underreporting. Type of progression Distant Any type (CI) Any type (1-KM) Local relapse (CI) Local relapse (1-KM) Lymph node (CI) Lymph node (1-KM) metastasis (CI) n=5,882 n=5,882 n=5,882 n=5,882 n=5,882 n=5,882 n=5,882 % % % % % % %

11 PROGRESSION ICD- C73: Thyroid cancer Page 11 of 15 Type of progression Distant cont'd metast. (1- NOS (CI) NOS (1-KM) KM) n=5,882 n=5,882 n=5,882 % % % Table 5b. Time to first progression of patients with thyroid cancer for period (N=5,882).

12 PROGRESSION ICD- C73: Thyroid cancer Page 12 of 15 ICD- C73: Malignant neoplasm of thyroid gland Progression type % Observed post-progression survival N= Figure 5c. Observed post-progression survival of 567 patients with thyroid cancer diagnosed between 1998 and 215. These 567 patients with documented progression events during their course of disease represent 9.2 % of the totally 6,132 evaluated cases (incl. M1, n=25, 4.1 %). Patients with cancer relapse documented via death certificates only were excluded (n=4, 1.7 %). Multiple progression types on different sites are included in the evaluation even when not occuring synchronously. The NOS (not otherwise specified) class is included under the condition, that it is the one and only progression type during the course of disease. Medical record documentation often lacks the linguistic severity to distinguish between local relapse, regional lymph node metastasis and distant spread in solid cancers. Frequently, the statement not specified is the only information in registries regarding relapse of the disease. The category Any type denotes all cases who suffered from at least one relapse during the course of disease (incl. primary M1-status). Although, the real number of relapsed patients is likely to be much higher. The accumulated percentage of patients with local relapse or distant metastasis exceeds the % value because patients are potientially considered in more than one subgroup. Type of progression Any type Local relapse Lymph node Distant metastasis NOS n=567 n=2 n=15 n=414 n=36 % % % % % Table 5d. Observed post-progression survival of patients with thyroid cancer for period (N=567). Type of progression Any type n=567.% Local relapse n=2 18.% Lymph node n= % Distant metastasis n= % NOS n=36 6.3%

13 PROGRESSION ICD- C73: Thyroid cancer Page 13 of 15 ICD- C73: Malignant neoplasm of thyroid gland Type of Progression: Distant metastasis % Observed post-progression survival by period of progression date N= Figure 5e. Observed post-progression (distant metastasis) survival of 549 patients with thyroid cancer diagnosed between 1988 and 215 by period of progression. Period of progression n=97 n=178 n=274 % % % Table 5f. Observed post-progression (distant metastasis) survival of patients with thyroid cancer for period by period of progression (N=549). Period of progression n= % n= % 27+ n= %

14 USAGE ICD- C73: Thyroid cancer Page 14 of 15 Shortcuts MCR Munich Cancer Registry, Germany NCI National Cancer Institute, USA SEER Surveillance, Epidemiology, and End Results, USA UICC Union for International Cancer Control, Geneva DCO Death certificate only NA Not available NOS Not otherwise specified Death certificate provides the only notification to the registry. OS Overall/Observed survival Overall/Observed survival (Kaplan-Meier estimate) Date of entry: diagnosis Event: death from any cause RS Relative survival Survival compared to general population, ratio of observed to expected survival (Ederer II method), reflecting cancer specific survival AS Assembled survival Assembled chart of observed, expected, relative survival CS Conditional survival Survival probability under the condition of surviving a given period of time TTP Time to progression Time to first progression / relapse Date of entry: diagnosis Event: (progression/ relapse): first local-, lymph node recurrence, distant metastasis or unspecified progression 1-KM CI 1 minus Kaplan-Meier estimator ( inverse Kaplan-Meier estimator) Cumulative incidence Death as competing risk (according to Kalbfleisch und Prentice) PPS Post-progression survival Survival since first progression / relapse (Kaplan-Meier estimate) Date of entry (progression / relapse): first local-, lymph node recurrence, distant metastasis or unspecified progression Event: death from any cause Recommended Citation Munich Cancer Registry. Survival ICD- C73: Thyroid cancer [Internet]. 217 [updated 217 Aug 22; cited 217 Oct 1]. Available from: E-ICD--C73- Thyroid-cancer-survival.pdf Copyright The content of the public web site provided by the Munich Cancer Registry is available worldwide and free of charge. All documents are free to download, utilize, copy, print-out and distribute, providing that the MCR is referenced. Disclaimer The Munich Cancer Registry reserves the right to not be responsible for the topicality, correctness, completeness or quality of the information provided. Liability claims regarding damage caused by the use of any information provided, including any kind of information which is incomplete or incorrect, will therefore be rejected.

15 INDEX ICD- C73: Thyroid cancer Page 15 of 15 Fig./Tbl. Index of figures and tables Page 1a Relative survival by period of diagnosis (chart) 2 1b Survival by period of diagnosis (table) 2 2a Survival by gender (chart) 3 2b Survival by gender (table) 3 3a Relative survival by age category (chart) 4 3b Survival by age category (table) 4 4a Relative survival by histology (chart) 5 4b Survival by histology (table) 5 4c Relative survival by (chart) 6 4d Survival by (table) 6 4e Relative survival by 27+ (chart) 8 4f Survival by 27+ (table) 8 4g Conditional survival by extent of disease (chart) 9 4h Conditional survival by extent of disease (table) 9 5a Time to first progression (chart) 5b Time to first progression (table) 5c Observed post-progression survival (chart) 12 5d Observed post-progression survival (table) 12 5e Observed post-progression survival by period of progression (chart) 13 5f Observed post-progression survival by period of progression (table) 13