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

Abstract

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.

Figure 1.. Forest Plot of the Included Studies Analyzing Recurrence Rates Among Patients With Multifocal vs Unifocal Disease

Abbreviation: NA, not applicable.

Figure 2.. Forest Plot of Subgroup Analysis (Tumor Size, Number of Foci, and Patient Age Group) of the Included Studies of Cancer-Specific Survival Rates Among Patients With Multifocal vs Unifocal Disease

NA indicates not applicable; PTMC, papillary thyroid microcarcinoma.

Figure 3.. Forest Plot of the Included Studies Analyzing Cancer-Specific Survival Rates Among Patients With Multifocal vs Unifocal Disease

Figure 4.. Funnel Plot Analysis of Recurrence Rates of Included Studies

Circles indicate the studies; the dotted line, no intervention effect; and the dashed line, pooled estimates.