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Original Investigation
August 19, 2021

Association of Multifocality With Prognosis of Papillary Thyroid Carcinoma: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Department of Surgery, Ewha Womans University Medical Center, Seoul, Republic of Korea
JAMA Otolaryngol Head Neck Surg. 2021;147(10):847-854. doi:10.1001/jamaoto.2021.1976
Key Points

Question  Does multifocality increase the risk of tumor recurrence in patients with papillary thyroid carcinoma?

Findings  In this systematic review and meta-analysis of 26 studies comprising 33 976 patients, multifocality was significantly associated with an increased risk of tumor recurrence.

Meaning  These findings suggest that papillary thyroid carcinoma with multifocality may require careful treatment and follow-up approaches.


Importance  Multifocality is common in papillary thyroid carcinoma (PTC), but it is unclear whether multifocal tumors are associated with tumor recurrence or cancer-specific survival.

Objective  To compare tumor recurrence rates in patients with multifocal vs unifocal PTCs.

Data Sources  We searched PubMed, SCOPUS, Web of Science Core Collection, and Cochrane Database of Systematic Reviews for pertinent studies published in English from inception to June 30, 2020.

Study Selection  The search strategy yielded 26 studies that compared tumor recurrence in patients with multifocal vs unifocal PTC.

Data Extraction and Synthesis  Data was extracted in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Characteristics of study populations and hazard ratio (HR) of multifocality were independently extracted by 2 investigators.

Main Outcomes and Measures  The primary outcome was tumor recurrence and the secondary outcome was cancer-specific survival. Subgroup analysis of the primary outcome was based on primary tumor size, number of tumor foci, and patient age.

Results  Among 26 studies with a total of 33 976 patients, recurrence rates were significantly higher in patients with multifocal PTC than in those with unifocal PTC (pooled HR, 1.81; 95% CI, 1.52–2.14). Cancer-specific survival was comparable between the groups (HR, 1.19; 95% CI, 0.85–1.68). In subgroup analyses, the HRs of multifocality for recurrence were associated with primary tumor size (HRs for PTC ≤1 cm and >1 cm were 1.81 and 1.90, respectively), number of tumor foci (HRs for 2 foci and ≥3 foci were 1.45 and 1.95, respectively), and patient age (HRs for pediatric and adult patients were 3.19 and 1.89, respectively).

Conclusions and Relevance  This systematic review with meta-analysis found that multifocality was significantly associated with an increased risk of recurrence in patients with PTC, while cancer-specific survival showed no difference. Differences in tumor size, number of tumor foci, and patient age should be considered when interpreting the multifocality and the risk of recurrence.

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