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

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 33976 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..