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Purpose <p>The clinical implications of the number of affected family members in familial non-medullary thyroid carcinoma (FNMTC) remain debated. This meta-analysis aimed to clarify whether families with ≥ 3 affected first-degree relatives (FNMTC-3) exhibit distinct clinicopathologic and prognostic features compared to families with two affected members (FNMTC-2), and to compare these patients with sporadic non-medullary thyroid carcinoma (SNMTC).</p> Methods <p>Following PRISMA guidelines, we systematically searched PubMed, Embase, and Cochrane Library for relevant studies. Meta-analysis was performed using RevMan 5.4 and Stata MP 18 to calculate pooled odds ratios (ORs), mean differences (MDs), and hazard ratios (HRs) with 95% confidence intervals (CIs).</p> Results <p>Twenty-one studies involving 3036 FNMTC and 10,497 SNMTC patients were included. Compared to SNMTC, both FNMTC-2 and FNMTC-3 exhibited younger age at diagnosis (MD: -0.81 and − 1.66 years), higher multifocality (OR: 1.48 and 1.91), bilaterality (OR: 1.53 and 1.48), lymph node metastasis (OR: 1.16 and 1.74), distant metastasis (OR: 2.43 and 3.93), and recurrence risks (OR: 1.29 and 1.49). Strikingly, FNMTC-3 demonstrated greater aggressiveness than FNMTC-2, including smaller tumor size (MD=-0.22&#xa0;cm, <i>p</i> = 0.007) but higher multifocality (OR = 1.26, <i>p</i> = 0.03), bilaterality (OR = 1.40, <i>p</i> = 0.004), lymph node metastasis (OR = 1.48, <i>p</i> = 0.002), distant metastasis risks (OR = 1.97, <i>p</i> = 0.01).</p> Conclusion <p>The clinical aggressiveness of FNMTC escalates with increasing numbers of affected family members. FNMTC-3 patients require more aggressive treatment and surveillance. While the current diagnostic criterion for FNMTC (≥ 2 affected members) remains clinically valid, families with ≥ 3 affected members should be classified as a high-risk subgroup, warranting individualized management strategies.</p>

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Relationship between affected family members and clinical aggressiveness in Familial non-medullary thyroid carcinoma: a systematic review and meta-analysis

  • 期刊论文

  • 发表日期：

    2025年9月4日

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  • Guang Yang,
  • Ye Tian,
  • Yujie Zhang,
  • Yanhao Ran,
  • Yuanyuan Fan,
  • Pengyu Li,
  • Xun Zheng,
  • Tao Wei

摘要

Purpose

The clinical implications of the number of affected family members in familial non-medullary thyroid carcinoma (FNMTC) remain debated. This meta-analysis aimed to clarify whether families with ≥ 3 affected first-degree relatives (FNMTC-3) exhibit distinct clinicopathologic and prognostic features compared to families with two affected members (FNMTC-2), and to compare these patients with sporadic non-medullary thyroid carcinoma (SNMTC).

Methods

Following PRISMA guidelines, we systematically searched PubMed, Embase, and Cochrane Library for relevant studies. Meta-analysis was performed using RevMan 5.4 and Stata MP 18 to calculate pooled odds ratios (ORs), mean differences (MDs), and hazard ratios (HRs) with 95% confidence intervals (CIs).

Results

Twenty-one studies involving 3036 FNMTC and 10,497 SNMTC patients were included. Compared to SNMTC, both FNMTC-2 and FNMTC-3 exhibited younger age at diagnosis (MD: -0.81 and − 1.66 years), higher multifocality (OR: 1.48 and 1.91), bilaterality (OR: 1.53 and 1.48), lymph node metastasis (OR: 1.16 and 1.74), distant metastasis (OR: 2.43 and 3.93), and recurrence risks (OR: 1.29 and 1.49). Strikingly, FNMTC-3 demonstrated greater aggressiveness than FNMTC-2, including smaller tumor size (MD=-0.22 cm, p = 0.007) but higher multifocality (OR = 1.26, p = 0.03), bilaterality (OR = 1.40, p = 0.004), lymph node metastasis (OR = 1.48, p = 0.002), distant metastasis risks (OR = 1.97, p = 0.01).

Conclusion

The clinical aggressiveness of FNMTC escalates with increasing numbers of affected family members. FNMTC-3 patients require more aggressive treatment and surveillance. While the current diagnostic criterion for FNMTC (≥ 2 affected members) remains clinically valid, families with ≥ 3 affected members should be classified as a high-risk subgroup, warranting individualized management strategies.