Multifocality is associated with an increased risk of recurrence in patients with papillary thyroid carcinoma (PTC), according to a meta-analysis published in JAMA Otolaryngology Head & Neck Surgery.

“Multifocality in thyroid cancer is defined as the simultaneous presence of more than 1 tumor focus within the thyroid gland,” the researchers wrote. 

They added that, although multifocality is common in PTC, it hasn’t been clear if multifocality is associated with tumor recurrence or cancer-specific survival. 

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To gain some insight, the researchers conducted a meta-analysis of 26 studies comparing tumor recurrence in patients with multifocal and unifocal PTC. A total of 33,976 patients were included in the analysis, and the median rate of multifocality was 28.1% (range, 6.4%-60.1%).

Patients with multifocal PTC had a significantly higher risk of recurrence than did patients with unifocal PTC (pooled hazard ratio [HR], 1.81; 95% CI, 1.52-2.14; P <.001). 

However, there was no significant difference in cancer-specific survival between the 2 groups (pooled HR, 1.19; 95% CI, 0.85-1.68; P =.31). 

The researchers conducted a subgroup analysis to evaluate potential sources of heterogeneity that might influence recurrence. They looked at primary tumor size (≤ 1 cm vs >1 cm), the number of tumor foci (2 vs ≥3), and patient age (pediatric [<20 years] vs adult).

The team found that multifocality was associated with a significantly increased risk of recurrence both for patients with tumors larger than 1 cm (pooled HR, 1.90; 95% CI, 1.11-3.25; P =.02) and for patients with tumors measuring 1 cm or less (pooled HR, 1.81; 95% CI, 1.18-2.77; P =.01).

Similarly, there was a significantly increased risk of recurrence for both pediatric patients (pooled HR, 3.19; 95% CI, 1.29-7.90; P =.01) and adult patients (pooled HR, 1.89; 95% CI, 1.06-3.38; P =.03). 

Multifocality was also associated with a significantly increased risk of recurrence for patients with 3 or more foci (pooled HR, 1.95; 95% CI, 1.33-2.85; P <.001). However, in patients with 2 foci, the increased risk of recurrence was not significant (pooled HR, 1.45; 95% CI, 0.97-2.17; P =.07).

Based on these results, the researchers recommended that tumor size, number of foci, and age “should be considered when determining treatment and follow-up approaches” in this patient population. 


Kim H, Kwon H, Moon B-I. Association of multifocality with prognosis of papillary thyroid carcinoma: A systematic review and meta-analysis. JAMA Otolaryngol Head Neck Surg. Published online August 19, 2021. doi:10.1001/jamaoto.2021.1976