Tumor Volume Kinetic Analyses Might Explain Excellent Prognoses in Young Patients with Papillary Thyroid Carcinoma

Young patients with papillary thyroid carcinoma (PTC) generally have excellent prognoses despite their often-advanced disease status. The reasons for this excellent prognosis are poorly understood.

To investigate the natural history of PTC in young patients, we compared the observed tumor volume-doubling rate (TV-DR) with the hypothetical tumor volume-doubling rate (hTV-DR) before presentation in young PTC patients. DR is an inverse of the doubling time and indicates the number of doublings that occur in a unit of time. A negative value indicates the number of times the volume is reduced by half per unit time.

We enrolled 20 patients with the following characteristics: age ≤19 years, diagnosed with PTC according to the cytology results between 2013 and 2018 and followed-up with periodical ultrasound examinations for ≥3 months before surgery for various reasons. Seventeen patients later underwent surgery confirming the diagnosis. We calculated TV-DRs using serial measurements of tumor diameters after presentation and hTV-DRs using tumor diameters and patients' age at presentation, assuming that a single cancer cell was present at the patient's birth and that the tumor grew at a constant rate. These values indicate the lowest growth rates necessary for a single cancer cell to achieve the full tumor size at presentation.

Thirteen patients had positive TV-DRs (/year) ranging from 0.09 to 1.89, indicating tumor growth, and the remaining seven patients had negative values (-0.08 to -1.21), indicating regression. The median TV-DR was 0.29. The hTV-DRs (1.48-2.66, median 1.71) were significantly larger than the TV-DRs (p < 0.001), indicating much faster growth before presentation.

These data suggest that deceleration of tumor growth had already occurred at presentation in the majority of the cases. This might explain why disease-specific survival is excellent despite frequent findings of advanced disease in young patients with PTC.