TOPLINE

A cohort study found that TERT promoter variants largely explained the poorer prognosis among older patients with papillary thyroid carcinoma. When patients aged 55 years or older had TERT wild-type tumors, 10-year disease-free survival topped 90%.

METHODOLOGY

• Age at diagnosis plays a key role in thyroid cancer prognostication, with patients aged 55 years or older staged differently from younger patients. TERT promoter variants, a consistent biomarker of aggressive thyroid cancer, are more common at older ages. Whether the poorer prognosis attributed to age is mediated through TERT promoter variants has been unclear.
• Researchers conducted a retrospective cohort study of 1555 patients treated for papillary thyroid carcinoma at three US academic centers. A total of 169 patients were included in survival analyses, with a median follow-up of 13.7 years.
• TERT promoter variants (C228T and C250T) were detected using polymerase chain reaction or targeted next-generation sequencing.
• The primary outcome was disease-specific survival, with a secondary outcome of progression-free survival. Mediation analysis was performed to assess whether the association between age 55 years or older and disease-specific survival was mediated through TERT promoter variants.

TAKEAWAY

• In the overall patient population, TERT promoter variants increased progressively with age, being rare in patients younger than 30 years (< 2%) and reaching a prevalence of 32%-70% in those older than 65 years.
• Among patients aged 55 years or older, 10-year disease-specific survival was 51% vs 91% for those with TERT promoter variants vs TERT wild-type tumors. A similar pattern was seen for 10-year progression-free survival.
• In multivariable analysis adjusting for age and pathologic tumor, node, and metastasis categories, TERT promoter variants remained independently associated with worse disease-specific survival (adjusted hazard ratio [AHR], 12.15), whereas the association between age and disease-specific survival was attenuated (AHR, 6.90).
• Mediation analysis demonstrated that approximately 82% of the total association between older age and disease-specific survival was mediated through TERT promoter variants.
• TERT promoter variants were associated with advanced tumor stage (3% T1/T2 vs 42% T3/T4; odds ratio [OR], 23.59), lymph node involvement (6% N0 vs 25% N1; OR, 4.76), and distant metastases (15% M0 vs 50% M1; OR, 5.40).

IN PRACTICE

According to the study authors, the findings “challenge the current reliance on strict age cutoffs” in the staging of thyroid cancer and suggest that TERT promoter variants better identify patients at risk of dying from the disease. “Integrating TERT status into risk stratification frameworks may better tailor treatment intensity and move the field toward more personalized care,” the study authors wrote.

SOURCE

The study, led by Vicente R. Marczyk, MD, PhD, and Jennifer R. Wang, MD, PhD, of MD Anderson Cancer Center in Houston, was published online in JAMA Otolaryngology-Head & Neck Surgery.

LIMITATIONS

The study was limited by its retrospective design and relatively modest sample size. Despite long-term follow-up, the number of disease-specific deaths was small. Residual confounding from treatment variation and unmeasured disease characteristics cannot be excluded.

DISCLOSURES

The study received support from the MD Anderson Petrick Thyroid Cancer Research Fund, American Society of Cytopathology, American Thyroid Association, National Institutes of Health, and the American Cancer Society. Several co-authors reported financial relationships with various commercial sources outside of the submitted work. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.