Surgical extent, tumor size, and calcitonin levels in medullary thyroid carcinoma: impact on oncologic outcomes in a retrospective cohort study

BACKGROUND: Medullary thyroid carcinoma (MTC) treatment guidelines recommend surgical extent based primarily on calcitonin levels, yet the oncologic impact of deviating from these protocols remains incompletely characterized. This study evaluates whether individualized treatment approaches based on comprehensive tumor characterization compromise disease outcomes compared to guideline-adherent management, and examines the relative importance of tumor size, calcitonin levels, and surgical extent in predicting persistent disease. METHODS: This retrospective cohort study included 91 patients with histologically confirmed MTC followed at a tertiary center from January 2019 to March 2025. Surgical procedures were compared against ATA-2015, ESMO-2019, and NCCN-2025 guideline recommendations and classified as concordant, less extensive, or more extensive. Primary outcomes included persistent disease, defined as biochemical or structural incomplete response occurring within 6 months of initial treatment; recurrent disease, defined as the reappearance of biochemical or structural disease more than 6 months after treatment in patients who had previously achieved an excellent response; reoperation rates; and postoperative complications. Associations between preoperative calcitonin levels and lymph node (LN) metastasis patterns were analyzed. Multivariable logistic regression identified independent predictors of persistent disease. RESULTS: Surgical procedures deviated from guidelines in 32.3% (ATA), 70.8% (ESMO), and 40.0% (NCCN) of cases. Deviation from guideline-recommended extent did not significantly impact persistent disease rates, reoperation requirements, or complication rates. Overall, 23.1% of patients had persistent disease at final follow-up. On multivariable analysis, independent predictors of persistent disease were higher preoperative calcitonin levels (OR 1.02 per 100 pg/mL increase, 95% CI 1.00-1.04, p = 0.042) and presence of LN metastasis (OR 4.52, 95% CI 1.01-20.24, p = 0.049), but not surgical extent classification. Primary tumor size correlated with metastatic involvement across all cervical compartments, while preoperative calcitonin levels predicted only ipsilateral lateral LN metastasis. A calcitonin threshold of 189.5 pg/mL predicted ipsilateral lateral metastasis with 92.3% sensitivity and 61.8% specificity. CONCLUSIONS: Individualized surgical approaches based on comprehensive preoperative assessment do not compromise oncologic outcomes when compared to guideline-adherent protocols. Disease persistence is determined by tumor biology rather than adherence to standardized surgical algorithms. Integration of tumor size with calcitonin measurements may improve risk stratification and enable treatment personalization while maintaining disease control.