Global Proposal for the TNM Staging System for Poorly Differentiated Thyroid Cancer

Poorly differentiated thyroid cancer (PDTC) lacks a dedicated staging system, requiring use of the eighth version of the American Joint Committee on Cancer and Union for International Cancer Control TNM staging system (TNM-8) for differentiated thyroid cancer despite its distinct biology.

To develop a PDTC-specific staging system.

This cohort study analyzed data from the International Aggressive Thyroid Cancer Collaborative Group (IATCCG), including surgically treated patients at 91 centers in 14 countries from January 1984 to January 2026. External validation was performed using patients from the US Surveillance, Epidemiology, and End Results (SEER) database. Data were analyzed from December 2025 to June 2026.

The primary end point was overall survival. With M1 disease predefined as stage IVB, the schema for stages I-IVA in patients with M0 disease were redefined. All possible TN combinations were fitted into multivariable Cox models, with the lowest Akaike information criterion defining the proposed system. Prognostic discrimination was assessed using adjusted hazard ratios (aHRs) and C statistics.

Among 1010 patients in the IATCCG cohort, 610 (60.4%) were female, and the median (IQR) age at diagnosis was 58 (46-68) years; median (IQR) follow-up was 41 (15-85) months. Among 170 patients in the SEER cohort, 85 (50.0%) were female, and the median (IQR) age at diagnosis was 61 (49-72) years; median (IQR) follow-up was 92 (42-154) months. In the IATCCG cohort, level VII lymph node metastasis (LNM) was associated with lower 5-year overall survival (45.2%; 95% CI, 33.4-61.2) than level VI (73.2%; 95% CI, 64.4-83.3) or lateral neck LNM (56.7%; 95% CI, 49.4-65.0). Level VII LNM was therefore reclassified from N1a to N1c. The lowest Akaike information criterion configuration among 16 738 candidates defined stages I to IVA as follows: I, T1N0/NX/N1a or T2N0/NX; II, T1N1b/N1c, T2N1a/N1b, or T3N0/NX/N1a; III, T2N1c, T3N1b, or T4aN0/NX/N1a; IVA, T3N1c, T4aN1b/N1c, or T4b any N; and IVB, M1 disease. Compared with TNM-8, stage I disease decreased from 44.4% (448 of 1010) to 24.6% (248 of 1010) and stage IV disease increased from 18.5% (187 of 1010) to 32.4% (327 of 1010) with the proposed system. The proposed staging had a higher C statistic than TNM-8 (0.74 [95% CI, 0.71-0.76] vs 0.71 [95% CI, 0.68-0.74]; difference, 0.03; 95% CI, 0.01-0.04). Corresponding SEER C statistic values were 0.76 (95% CI, 0.71-0.81) vs 0.74 (95% CI, 0.68-0.79), respectively (difference, 0.02; 95% CI, -0.01 to 0.06).

This cohort study found that this PDTC-specific staging system provides improved prognostic stratification reflecting its different biology. These data provide a strong rationale for the potential inclusion of a stand-alone American Joint Committee on Cancer staging system for PDTC.