The newest edition of the thyroid cancer staging system has increased the age at diagnosis as a prognostic factor by a decade. To understand the impact of this, and other recent changes, we staged patients using our extensive, prospectively collected database at Memorial Sloan Kettering Cancer Center based on both the current edition and previous one.
The eighth edition of the American Joint Committee on Cancer (AJCC) has also updated the definitions of T3, T4, and nodal staging.
It is important to note that the staging system for thyroid cancer is unique. It is the only human cancer where age at diagnosis is an independent prognostic factor. Previously, the age of 45 was used as a cut off point for dividing patients into low- and high-risk groups, along with other factors. There was no stage III or stage IV for patients under 45 because mortality rates were so low for those patients.
In our retrospective analysis, published recently in the journal Surgery, we reported that 29 percent of 3,650 patients were downgraded in stage using the eighth edition guidelines. Overall, the new staging system more accurately reflected the biology of the disease, with a more appropriate correlation and stratification for cancer-specific, overall, and recurrence-free survival. (1)
We anticipate that adopting the eighth edition of the AJCC staging system will help us better understand patients’ prognoses and make better decisions about who will require adjuvant treatment.
Thyroid Cancer
The incidence of thyroid cancer in the United States has almost quadrupled over the last 25 years, from about 8,000 patients to 54,000. (2) However, mortality has remained relatively stable. (3)
Thyroid cancer is unique among human cancers because the selection of therapy and outcomes depend on prognostic factors and risk group analysis. The prognostic factors that play critical roles in disease evaluation and management are age, histology, extrathyroidal extension, tumor size, and distant metastases. This same list of prognostic factors is repeated in separate data sets from MSK, (4) the Mayo Clinic, (5) Lahey Health, (6) and the European Organisation for Research and Treatment of Cancer. (7)
Each of these institutions has analyzed their data and defined prognostic factors that divide patients into low-, intermediate-, and high-risk groups. The ten-year disease-specific survival rates are higher than 99 percent for the low-risk group, 86 to 87 percent in the intermediate-risk group, and 78 percent in the high-risk group. (4)
The Staging System for Thyroid Cancer Is Unique
The overall goals of staging cancer are to define prognostic groups of patients and vary the treatment approach for each group to achieve the best outcomes. Typically, cancers are characterized according to four stages, where stages I and II are considered early cancers with excellent outcomes after unimodal treatment. Patients with stages III or IV cancers typically require multimodal therapy, and survival rates drop to about 40 to 50 percent.
The AJCC tumor, node, and metastasis (TNM) system has become popular and is essentially an initial clinical staging system.
Surgeon Iain Nixon along with MSK and international colleagues reviewed the database of MSK patients with thyroid cancer in 2016 and validated age 55 as a better cutoff point than age 45. (8) The landmark study, combined with data from other centers around the world, led the AJCC to change the cutoff age to 55 in the eighth edition staging for thyroid cancer.
Changes in the Eighth Edition Staging System for Thyroid Cancer
Major changes in the eighth edition compared to the seventh edition are as follows:
- The cut-off age has been increased from 45 to 55.
- Minor extrathyroid extension was removed from the definition of T3.
- N1 disease does not upgrade the tumor to stage III.
- Tumors more than four centimeters that are confined to the thyroid are classified as T3a.
- T3b tumors are of any size with gross extrathyroidal extension into strap muscles.
- Level VII nodes (N1b) are not considered stage IV.
- Distant metastases are considered stage IVB, not stage IVC.
Study Results
For our retrospective analysis, we staged patients in the MSK database using both the seventh and eighth editions to determine the major reclassification changes with the new age cutoff and definitions of T3 and T4 primary tumors and nodal staging. The MSK database contains prospectively collected patient data, with detailed information on prognostic factors and treatment outcomes.
Our results showed that of 3,650 patients, 1,057 (29 percent) were downgraded. Of 281 patients with stage IV disease, 104 (10 percent) were downgraded to stage I, 109 (10 percent) to stage II, and 68 (6 percent) to stage III. Of 565 patients with stage III disease, 218 (21 percent) were downgraded to stage I and 347 (37 percent) to stage II. There were 211 (20 percent) patients with stage II disease who were downgraded to stage I. (1)
We also examined survival rates with both staging systems. Overall, disease-specific and recurrence-free survival showed a more appropriate correlation and stratification with the eighth edition. The eighth edition staging system also more accurately reflects the biology of the disease, with a better spread of survival curves between stages I, II, III, and IV, unlike the seventh edition, which lumped stages I, II, and III together and only showed a survival difference in stage IV. (1)
Improved Staging for Improved Patient Outcomes
Decisions about the extent of thyroidectomy and adjuvant therapy, such as radioactive iodine, are primarily based on risk group stratification. The eighth edition of the AJCC staging system for thyroid cancer effectively stratifies patients into stage groups that correlate well with overall prognosis. We anticipate that the adoption of this new staging system will improve patient outcomes at MSK and around the world.
At MSK, we are committed to advancing innovative research for all stages of thyroid cancer. Understanding the biology of the disease informs the development of individualized treatment plans for all patients.
MSK physicians and researchers have led many discoveries about how and why thyroid cancer develops, including characterizing the genetic mutations that may predict responsiveness to radioactive iodine therapy and the likelihood of metastases, and comprehensive genomic studies on anaplastic and poorly differentiated thyroid cancer that are paving the way for the development of new treatments.
We are currently conducting ten clinical trials for patients with thyroid cancer to test a variety of promising chemotherapies and immunotherapies.
The study was supported by a National Institutes of Health P30 Cancer Support Grant (CCSG; P30 CA008748).
The authors declare no conflicts of interest.
