Clinical Endocrinology (2014) 80, 911–917
doi: 10.1111/cen.12405
ORIGINAL ARTICLE
No significant difference in the prognostic value of the 5th and 7th editions of AJCC staging for differentiated thyroid cancer Alexis Vrachimis*, Joachim Gerss†, Maren Stoyke‡, Christian Wittekind§, Tobias Maier*, Christian Wenning*, Kambiz Rahbar*, Otmar Schober* and Burkhard Riemann* *Department of Nuclear Medicine, †Institute of Biostatistics and Clinical Research, University Hospital M€ unster, M€ unster, ‡Clinic for Neurology and Clinical Neurophysiology, Herz-Jesu-Hospital, M€ unster-Hiltrup and §Institute of Pathology, University Hospital Leipzig, Leipzig, Germany
Introduction Summary
AV and JG contributed equally.
Differentiated thyroid cancer (DTC) has an excellent prognosis, with 10-year survival rates over 90%.1–6 For staging of these carcinomas, the tumor node metastasis (TNM) classification of the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) is most commonly and widely accepted. The fifth edition (1997) was revised to the sixth (2002; updated 2003) and the current seventh edition (2009). To adapt the classification of thyroid cancer to other head and neck tumours, the tumour (T) and lymph node (N) categories were revised in the editions of 2002 and 2009.7–9 The T categories are based both on tumour size and on extrathyroid extension. In the previous fifth edition, tumours extending beyond the thyroid capsule were graded as T4 at any degree of extension.7 In the most recent editions (sixth and seventh), tumours with massive extrathyroid extension to subcutaneous soft tissues, larynx, trachea, oesophagus or recurrent laryngeal nerve are classified as T4a, while those with only minimal extrathyroidal extension to the sternothyroid muscle or perithyroid soft tissues are staged as T3.8,9 Lymph node metastasis is classified in the sixth and seventh editions into two categories: patients having metastasis only to the central compartment are graded as N1a and those having metastasis to the lateral or mediastinal compartments are graded as N1b. In 2009, the AJCC seventh edition for thyroid cancer was released and included only minor changes in regard to the T staging, i.e. subcategories of T1 to T1a and T1b and the descriptors of the T category to include single and multiple tumours, resulting in no further stage migration.9 Few previous studies have focused on the sixth edition of AJCC and have evaluated solely the disease-specific survival (DSS) on a limited number of patients.10–12 Ito et al.13 have validated both DSS and event-free survival (EFS) of the sixth classification in a large number of patients, although exclusively for papillary thyroid carcinoma (PTC) and without any comparison with the previous AJCC edition. Recently, Maxner et al. compared the fifth and the seventh editions of the AJCC classification only with regard to T category. As outcome
© 2014 John Wiley & Sons Ltd
911
Objective The seventh edition of the American Joint Committee on Cancer (AJCC) has more detailed staging categories for differentiated thyroid cancer (DTC) than the fifth edition. The aim was to compare potential alterations in the disease-specific (DSS), event-free (EFS) and overall survival (OS), after reclassification from the fifth to the seventh edition. Methods Data of 2460 patients with DTC referred to our centre were reclassified from the fifth to the seventh edition of AJCC. DSS, EFS and OS were calculated using the Kaplan-Meier method and compared by the log-rank test. The relative abilities of each edition to predict survival were calculated by the proportion of variance explained (PVE). Results After reclassification to the seventh edition, there was an increase in stage I and IV patients from 581% to 650% and from 62% to 101%, respectively, and a corresponding decrease in stage II and III patients from 224% to 125% and 133% to 124%, respectively. As to DSS, the seventh edition had only a marginally higher PVE value than the fifth edition. With respect to EFS, the predictability of the seventh edition was even inferior to that of the fifth edition. Similarly, with regard to OS, the PVE value was slightly better for the older edition. Furthermore, a comparison only for those patients affected by the reclassification revealed no differences for DSS, EFS or OS between classifications. Conclusion When comparing the stages of the seventh with the fifth edition of the AJCC for DTC, there was no significant difference in predicting DSS, EFS and OS. (Received 3 October 2013; returned for revision 7 December 2013; finally revised 2 January 2014; accepted 4 January 2014)
Correspondence: Alexis Vrachimis, MD, Department of Nuclear Medicine, University Hospital of M€ unster, Albert-Schweitzer-Campus 1, Building A1, 48149 M€ unster, Germany. Tel.: +49(0)2518347362; E-mail: [email protected]
912 A. Vrachimis et al. parameters, solely EFS was observed in relative small number of patients.14 In a parallel study, Wong et al.15 compare various staging systems including the two above-mentioned AJCC classification systems with regard to PVE and C-index in a large databank composed primarily of PTC patients. The aim of our study was to compare the prognostic predictability of the classification system in the fifth and seventh editions of the AJCC in respect of DSS, EFS and overall survival (OS) using a large cohort of DTC patients.
for example on needle aspiration biopsy and more intensive follow-up examinations as well as F-18-FDG-PET(/CT), were taken. In case of locoregional recurrence, such as lateral lymph node metastases, early surgical reintervention with compartment-oriented lymphadenectomy was considered the primary therapeutic option.20 However, final decisions were reached on an individual basis taking into account the risk of surgical complications and alternative options such as radioiodine therapy of small iodine-avid lesions.
Meterials and methods
Methods
Two thousand four hundred and sixty (1816 females; mean age at diagnosis 475 155 years) of a total of 2583 consecutive patients identified in our electronic database, with pathologically diagnosed differentiated thyroid cancer after thyroidectomy (TE), referred to the University Hospital of M€ unster in the period January 1966 to April 2013 were selected for this retrospective analysis. One hundred and seven non-DTC patients were excluded. Also excluded were nine further patients that could not be classified to the fifth and/or the seventh and seven patients with unknown date of last contact. There were 1846 (750%) patients with PTC, 578 (235%) with follicular thyroid carcinoma (FTC) and 36 with poorly differentiated thyroid carcinoma (PDTC).
The study categorization in the TNM classification was made according to the fifth and seventh AJCC/UICC classifications after successful ablation of thyroid rests with radioiodine if applicable.7,9 For the reclassification, surgery and histology reports were obtained from the patient records. Follow-up data were also obtained from the patient records of our clinic and from the family doctors of the patients. Cause of death was based on death certificate reports. Disease-specific survival, EFS and OS were calculated for the TNM stages for the same patient group separately for AJCC 1997 and AJCC 2009. The Joint Research Ethics Committee of the Faculty of Medicine, University of M€ unster, and the loco-regional Chamber of Physicians of Westfalen-Lippe confirmed that no ethics committee review was required for this study under the applicable law.
Surgical treatment and radioiodine therapy
Statistical analysis
Total or near-total thyroidectomy was performed in 2227 patients (905%), whereas the remainder underwent more limited thyroidectomy (subtotal thyroidectomy 80%; lobectomy 15%). Two thousand two hundred and ninety-four (932%) patients had histologically tumour-free resection margins; 129 (52%) had microscopic and 37 (15%) macroscopic tumour residuals. Post-operative radioiodine remnant ablation was applied to 993%, 972% and 882% of the patients with FTC, PDTC and PTC, respectively. Additional radioiodine wholebody scan was performed in the follow-up period of these patients. The vast majority of the 218 PTC patients not receiving RIA had microcarcinomas (n = 198). The remaining patients (AJCC 2009 stages I n = 12; II n = 1; III n = 3; IVA n = 2) refused further treatment because of radiophobia. All patients were submitted to thyroid-stimulating hormone (TSH) suppression therapy.
Survival was calculated from the date of initial surgery to the date of death or last follow-up (DSS) or to the date of an event (EFS) or death (OS). An event was defined as local relapse, lymph node or distant metastasis or death after prior stimulated serum thyroglobulin 90% of the population studied. As © 2014 John Wiley & Sons Ltd Clinical Endocrinology (2014), 80, 911–917
© 2014 John Wiley & Sons Ltd Clinical Endocrinology (2014), 80, 911–917
Fifth edition TNM Stage I: M0 (
doi: 10.1111/cen.12405
ORIGINAL ARTICLE
No significant difference in the prognostic value of the 5th and 7th editions of AJCC staging for differentiated thyroid cancer Alexis Vrachimis*, Joachim Gerss†, Maren Stoyke‡, Christian Wittekind§, Tobias Maier*, Christian Wenning*, Kambiz Rahbar*, Otmar Schober* and Burkhard Riemann* *Department of Nuclear Medicine, †Institute of Biostatistics and Clinical Research, University Hospital M€ unster, M€ unster, ‡Clinic for Neurology and Clinical Neurophysiology, Herz-Jesu-Hospital, M€ unster-Hiltrup and §Institute of Pathology, University Hospital Leipzig, Leipzig, Germany
Introduction Summary
AV and JG contributed equally.
Differentiated thyroid cancer (DTC) has an excellent prognosis, with 10-year survival rates over 90%.1–6 For staging of these carcinomas, the tumor node metastasis (TNM) classification of the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) is most commonly and widely accepted. The fifth edition (1997) was revised to the sixth (2002; updated 2003) and the current seventh edition (2009). To adapt the classification of thyroid cancer to other head and neck tumours, the tumour (T) and lymph node (N) categories were revised in the editions of 2002 and 2009.7–9 The T categories are based both on tumour size and on extrathyroid extension. In the previous fifth edition, tumours extending beyond the thyroid capsule were graded as T4 at any degree of extension.7 In the most recent editions (sixth and seventh), tumours with massive extrathyroid extension to subcutaneous soft tissues, larynx, trachea, oesophagus or recurrent laryngeal nerve are classified as T4a, while those with only minimal extrathyroidal extension to the sternothyroid muscle or perithyroid soft tissues are staged as T3.8,9 Lymph node metastasis is classified in the sixth and seventh editions into two categories: patients having metastasis only to the central compartment are graded as N1a and those having metastasis to the lateral or mediastinal compartments are graded as N1b. In 2009, the AJCC seventh edition for thyroid cancer was released and included only minor changes in regard to the T staging, i.e. subcategories of T1 to T1a and T1b and the descriptors of the T category to include single and multiple tumours, resulting in no further stage migration.9 Few previous studies have focused on the sixth edition of AJCC and have evaluated solely the disease-specific survival (DSS) on a limited number of patients.10–12 Ito et al.13 have validated both DSS and event-free survival (EFS) of the sixth classification in a large number of patients, although exclusively for papillary thyroid carcinoma (PTC) and without any comparison with the previous AJCC edition. Recently, Maxner et al. compared the fifth and the seventh editions of the AJCC classification only with regard to T category. As outcome
© 2014 John Wiley & Sons Ltd
911
Objective The seventh edition of the American Joint Committee on Cancer (AJCC) has more detailed staging categories for differentiated thyroid cancer (DTC) than the fifth edition. The aim was to compare potential alterations in the disease-specific (DSS), event-free (EFS) and overall survival (OS), after reclassification from the fifth to the seventh edition. Methods Data of 2460 patients with DTC referred to our centre were reclassified from the fifth to the seventh edition of AJCC. DSS, EFS and OS were calculated using the Kaplan-Meier method and compared by the log-rank test. The relative abilities of each edition to predict survival were calculated by the proportion of variance explained (PVE). Results After reclassification to the seventh edition, there was an increase in stage I and IV patients from 581% to 650% and from 62% to 101%, respectively, and a corresponding decrease in stage II and III patients from 224% to 125% and 133% to 124%, respectively. As to DSS, the seventh edition had only a marginally higher PVE value than the fifth edition. With respect to EFS, the predictability of the seventh edition was even inferior to that of the fifth edition. Similarly, with regard to OS, the PVE value was slightly better for the older edition. Furthermore, a comparison only for those patients affected by the reclassification revealed no differences for DSS, EFS or OS between classifications. Conclusion When comparing the stages of the seventh with the fifth edition of the AJCC for DTC, there was no significant difference in predicting DSS, EFS and OS. (Received 3 October 2013; returned for revision 7 December 2013; finally revised 2 January 2014; accepted 4 January 2014)
Correspondence: Alexis Vrachimis, MD, Department of Nuclear Medicine, University Hospital of M€ unster, Albert-Schweitzer-Campus 1, Building A1, 48149 M€ unster, Germany. Tel.: +49(0)2518347362; E-mail: [email protected]
912 A. Vrachimis et al. parameters, solely EFS was observed in relative small number of patients.14 In a parallel study, Wong et al.15 compare various staging systems including the two above-mentioned AJCC classification systems with regard to PVE and C-index in a large databank composed primarily of PTC patients. The aim of our study was to compare the prognostic predictability of the classification system in the fifth and seventh editions of the AJCC in respect of DSS, EFS and overall survival (OS) using a large cohort of DTC patients.
for example on needle aspiration biopsy and more intensive follow-up examinations as well as F-18-FDG-PET(/CT), were taken. In case of locoregional recurrence, such as lateral lymph node metastases, early surgical reintervention with compartment-oriented lymphadenectomy was considered the primary therapeutic option.20 However, final decisions were reached on an individual basis taking into account the risk of surgical complications and alternative options such as radioiodine therapy of small iodine-avid lesions.
Meterials and methods
Methods
Two thousand four hundred and sixty (1816 females; mean age at diagnosis 475 155 years) of a total of 2583 consecutive patients identified in our electronic database, with pathologically diagnosed differentiated thyroid cancer after thyroidectomy (TE), referred to the University Hospital of M€ unster in the period January 1966 to April 2013 were selected for this retrospective analysis. One hundred and seven non-DTC patients were excluded. Also excluded were nine further patients that could not be classified to the fifth and/or the seventh and seven patients with unknown date of last contact. There were 1846 (750%) patients with PTC, 578 (235%) with follicular thyroid carcinoma (FTC) and 36 with poorly differentiated thyroid carcinoma (PDTC).
The study categorization in the TNM classification was made according to the fifth and seventh AJCC/UICC classifications after successful ablation of thyroid rests with radioiodine if applicable.7,9 For the reclassification, surgery and histology reports were obtained from the patient records. Follow-up data were also obtained from the patient records of our clinic and from the family doctors of the patients. Cause of death was based on death certificate reports. Disease-specific survival, EFS and OS were calculated for the TNM stages for the same patient group separately for AJCC 1997 and AJCC 2009. The Joint Research Ethics Committee of the Faculty of Medicine, University of M€ unster, and the loco-regional Chamber of Physicians of Westfalen-Lippe confirmed that no ethics committee review was required for this study under the applicable law.
Surgical treatment and radioiodine therapy
Statistical analysis
Total or near-total thyroidectomy was performed in 2227 patients (905%), whereas the remainder underwent more limited thyroidectomy (subtotal thyroidectomy 80%; lobectomy 15%). Two thousand two hundred and ninety-four (932%) patients had histologically tumour-free resection margins; 129 (52%) had microscopic and 37 (15%) macroscopic tumour residuals. Post-operative radioiodine remnant ablation was applied to 993%, 972% and 882% of the patients with FTC, PDTC and PTC, respectively. Additional radioiodine wholebody scan was performed in the follow-up period of these patients. The vast majority of the 218 PTC patients not receiving RIA had microcarcinomas (n = 198). The remaining patients (AJCC 2009 stages I n = 12; II n = 1; III n = 3; IVA n = 2) refused further treatment because of radiophobia. All patients were submitted to thyroid-stimulating hormone (TSH) suppression therapy.
Survival was calculated from the date of initial surgery to the date of death or last follow-up (DSS) or to the date of an event (EFS) or death (OS). An event was defined as local relapse, lymph node or distant metastasis or death after prior stimulated serum thyroglobulin 90% of the population studied. As © 2014 John Wiley & Sons Ltd Clinical Endocrinology (2014), 80, 911–917
© 2014 John Wiley & Sons Ltd Clinical Endocrinology (2014), 80, 911–917
Fifth edition TNM Stage I: M0 (
