What Is the Ideal Age Cutoff for Papillary and Follicular Thyroid Cancer Staging, and Should the Cutoffs Be Different?

• Clin Thyroidol 2021;33:177–179.
• Background:
  • The Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging system:
    • Is designed to predict disease-specific survival
    • Differentiated thyroid cancer (DTC) is the only malignancy that includes an age cutoff in determining stage within this system
  • The previous AJCC 7th edition used an age cutoff of 45 years:
    • In which patients under the age of 45 could not be staged higher than stage II
  • While the updated 8th edition now uses 55 years:
    • As this threshold for both papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC)
  • Multiple studies have shown age 55 years to be superior to 45 years as a cutoff for DTC, but questions remain on other potential age cutoffs for DTC
  • PTC and FTC are staged together as DTC, given their similar disease-specific survival:
    • Yet it has not been established whether PTC and FTC should have the same age cutoff, given that they can have different clinical courses:
      • PTC is more likely to have regional lymph node metastasis and FTC to have distant metastasis
  • The present study aims to investigate the optimal cutoff for the TNM staging the system for DTC, using the histopathologic criteria of the 8th edition, and also to examine optimal age cutoffs for both PTC and FTC
• Methods
  • The current study is a retrospective analysis of two well-established databases from The Netherlands and Germany
  • Patients were age 18 years and above who were treated for either PTC or FTC between 2002 and 2016 (Erasmus Medical Center database) or between 1980 and 2015 (University of Würzburg database)
  • All patients underwent thyroid surgery and were treated according to standards at the time
  • Demographic, disease, treatment, and mortality data were obtained
  • Patients were reclassified using the histopathologic criteria from the TNM 8th edition with different age cutoffs
  • Age cutoffs were analyzed at 5-year increments from 20 up to 85 years and by 1-year increments between 35 and 55 years
  • Analysis was done for the combined DTC patient population and separately for PTC and FTC
  • Disease-specific survival was analyzed using the Kaplan–Meier method and compared across stages using the log-rank test
  • The concordance index (Harrell’s C-index), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were used to assess the statistical model performance at different age cutoffs
  • The model with the highest C-index and lowest AIC and BIC was considered to be the best
• Results
  • A total of 3074 patients were included (820 from Erasmus Medical Center and 2254 from University of Würzburg)
  • Of these patients, 2355 (77%) had PTC and 719 (23%) had FTC, with a median follow-up of 84 months
  • The mean age was 48.7 years, and 69.5% were female
  • Overall, 23.1% had lymph node metastasis and 8.8% had distant metastasis
  • When compared to patients with PTC, patients with FTC:
    • Were older (54.2 years vs. 47.1 years; P<0.001), more likely to be male (37.1% vs. 28.5%; P<0.001), less likely to have lymph node metastasis (9.2% vs. 27.3%; P<0.001), and more likely to have distant metastasis (18.2% vs. 6.0%; P<0.001)
  • Using the 8th edition’s age cutoff of 55 years, 2430 patients (79%) were classified as stage I, 384 (13%) as stage II, 88 (3%) as stage III, and 172 (6%) as stage IV
  • Lowering the age cutoff :
    • Lowered the number of patients in stage I
  • Increasing the age cutoff:
    • Increased the number of patients in stage
  • The 10-year disease-specific survival for DTC was 94.7% and was significantly higher for patients with PTC than for those with FTC (96.5% vs. 89.5%; P<0.001)
  • For DTC, PTC, and FTC, the majority of age cutoffs performed better in the statistical model than did no age cutoff
  • Using 5-year increments for the age cutoffs:
    • DTC and PTC had the best performance, with an age cutoff of 50 years
    • While FTC was 40 years
  • Using 1-year increments:
    • DTC performed best, at an age cutoff of 50 years, PTC at 48 years, and FTC at 41 years
• Conclusions
  • When using the histopathologic criteria of the 8th edition TNM system:
    • The optimal age cutoff for DTC to predict disease-specific survival is 50 years, rather than 55 years as is currently in use
    • The optimal age cutoff for PTC is also 50 years
    • While the age cutoff for FTC should be 40 years:
      • Signifying that the age cutoffs for PTC and FTC should be different

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