Abstract
KEY POINTS
In carefully selected patients with unilateral, germline RET-negative medullary thyroid carcinoma (MTC), lobectomy with central neck dissection may achieve outcomes comparable to those of total thyroidectomy.
Mortality, overall survival, biochemical cure, and distant metastasis rates did not differ between lobectomy and total thyroidectomy in pooled analyses.
Total thyroidectomy carries a higher risk of postoperative complications without consistent long-term oncologic advantage.
SUMMARY
Background
Sporadic medullary thyroid carcinoma (MTC) accounts for approximately 80% of MTCs. Several guidelines, including those of the American Thyroid Association, 1 the European Society for Medical Oncology, 2 and the British Thyroid Association, 3 recommend total thyroidectomy as the initial standard surgical approach. The incidence of contralateral involvement is low in unilateral, germline RET-negative tumors, ranging between 0 and 9%. 4 The Japan Association of Endocrine Surgery guidelines explicitly recommend lobectomy for unilateral sporadic MTC, 5 and the most recent updates of the National Comprehensive Cancer Network 6 and of German guidelines 7 suggest considering lobectomy in carefully selected patients with unilateral sporadic MTC. Consequently, the optimal extent of surgery in selected patients with unilateral sporadic MTC remains uncertain, and high-quality evidence is still lacking. The present study is a systematic review and meta-analysis of retrospective studies to compare oncologic outcomes between total thyroidectomy and lobectomy for sporadic MTC. 8 This work aims to determine whether less extensive surgery can provide equivalent long-term outcomes, potentially reducing operative morbidity and lifelong thyroid hormone dependence, and to inform shared decision-making in clinical practice.
Methods
The authors conducted a comprehensive literature search of MEDLINE, Embase, Scopus, and the Cochrane Central Register from inception to December 2025. Eligible studies included patients with histologically confirmed unilateral sporadic MTC undergoing either total thyroidectomy or lobectomy (including hemithyroidectomy), with or without central neck dissection, and reported on oncologic outcomes. Exclusion criteria included hereditary MTC, prior systemic therapy, or distant metastases at diagnosis. Primary outcomes were mortality, overall survival, structural recurrence, biochemical cure, and development of distant metastasis; postoperative complications were secondary outcomes. Data extraction and risk-of-bias assessment were performed independently by multiple reviewers. Meta-analyses were conducted using random-effects models, calculating odds ratios or relative risks with 95% confidence intervals. Sensitivity analyses were performed based on RET mutation status and study definitions of sporadic disease. Heterogeneity was assessed using I2 statistics, and certainty of evidence was evaluated with Grading of Recommendations Assessment, Development, and Evaluation principles.
Results
Nine retrospective studies, including 1371 patients, met inclusion criteria. Of these patients, 531 (38.7%) underwent lobectomy and 840 (61.3%) underwent total thyroidectomy. Central neck dissection was performed in 445 of 492 patients (90.4%), multifocality was reported in 30 of 330 patients (9.1%), 284/401 tumors (70.8%) were smaller than 2 cm, and 197/343 (57.4%) were N0. The number of patients varies across outcomes because not all included studies provided complete information for each variable. Patients treated by total thyroidectomy more frequently had postoperative complications. Mortality at 5 years and beyond did not differ between surgical groups (RR, ≤ 5 years, 0.30; [CI, 0.07–1.35]; RR > 5 years, 1.00; [CI, 0.40–2.47]). Overall survival at 5 years was similar (RR, 1.02; [CI, 0.94–1.11]). Structural recurrence showed no consistent difference at 5 years (OR, 0.45; [CI, 0.14–1.49]), and longer-term analyses suggested higher odds in total thyroidectomy, though sensitivity analyses, excluding studies that defined sporadic cases clinically, did not confirm this difference. Biochemical cure and distant metastasis rates did not differ between groups. Postoperative complications, including hypoparathyroidism and recurrent laryngeal-nerve injury, were more frequent after total thyroidectomy. Risk of bias was moderate to high in most studies, with overall certainty of evidence rated low in one study owing to study-design limitations, heterogeneity, and short follow-up durations.
Conclusions
In selected patients with unilateral, germline RET-negative MTC, lobectomy plus ipsilateral central neck dissection may provide oncologic outcomes comparable to total thyroidectomy, with a lower risk of postoperative complications. These findings support consideration of a more conservative surgical approach in appropriately selected patients, while emphasizing careful preoperative diagnostic workup and shared decision-making.
COMMENTARY
This systematic review and meta-analysis provides an important synthesis of current evidence regarding the optimal surgical management of sporadic MTC. The findings are particularly relevant in light of long-standing guidelines recommending total thyroidectomy, which have historically prioritized prevention of contralateral disease over individualized risk assessment. The data suggest that, in patients with small, unilateral, germline RET-negative tumors, lobectomy combined with appropriate central neck dissection may achieve comparable long-term oncologic outcomes while reducing surgical morbidity. From a biological perspective, sporadic MTC typically originates from a single parafollicular C cell, and contralateral involvement is uncommon in germline RET-negative cases. A multicenter study of genetically confirmed sporadic MTC reported bilateral disease in 8% of cases, while occult bilateral disease was reported in only 2% of cases, decreasing to less than 1% in tumors smaller than 2 cm. 9 Furthermore, analyses from large national databases indicate that overall survival is more strongly associated with tumor characteristics and patient age than with the extent of surgery.
In my clinical practice, in which serum calcitonin is routinely measured during the evaluation of thyroid nodules, earlier detection of small, less aggressive sporadic MTC is increasingly common. Historically, total thyroidectomy has been almost universally performed, exposing patients to risks such as permanent hypoparathyroidism and recurrent laryngeal-nerve injury. More recently, in carefully selected germline RET-negative patients, where a solitary tumor focus is clearly identified and no contralateral disease is evident, lobectomy with ipsilateral central neck dissection has been adopted with favorable outcomes. The findings of this meta-analysis support the validity of this more conservative approach. Nevertheless, the low certainty of the available evidence, largely due to retrospective study designs and heterogeneity among studies, warrants caution. Prospective registries and collaborative multicenter investigations are needed to better define the long-term safety and oncologic adequacy of lobectomy in sporadic MTC.
In conclusion, this review supports a shift toward a more tailored surgical strategy in sporadic MTC, balancing oncologic efficacy with quality of life. Total thyroidectomy remains the standard of care for higher-risk or hereditary cases; however, lobectomy represents a safe and reasonable alternative in selected patients with low-risk, unilateral disease and may facilitate more informed shared decision-making.