Trends in Incidence, Care, and Surgery for Medullary Thyroid Cancer: A Review

Abstract

Medullary thyroid carcinoma (MTC) is an uncommon but biologically distinct cancer originating from parafollicular C cells of the thyroid. Its management has been influenced to a great extent by advances in molecular genetics, improved diagnostic approaches, and the refinement of surgical techniques. There is a clear trend toward stable evolution in MTC incidence. This has mainly been driven by increased awareness and genetic screening of familial cases. Further improvement in outcomes has been seen with centralized care delivery models and multidisciplinary approaches through early detection and personalized treatment plans. Surgery is the cornerstone of MTC management, with total thyroidectomy and precise lymph node dissection tailored based on the extent of disease and genetic risk profiles. Despite all these advances, challenges persist in optimizing care for metastatic and recurrent disease and addressing disparities in access to specialized care. Review the trends that shape the incidence, organization of care, and surgical treatment for patients with MTC, advocating the incorporation of molecular developments, innovations in surgery, and systemic treatments into the evolving horizon of the management of MTC.

Introduction

Medullary thyroid cancer (MTC) represents approximately 1–2% of all thyroid malignancies but is clinically and biologically important due to its aggressive nature and association with hereditary syndromes, such as multiple endocrine neoplasia type 2 (MEN2). The molecular underpinnings of MTC, particularly mutations in the rearranged during transfection (RET) proto-oncogene, have revolutionized its diagnosis, prognostication, and management. Though surgery remains the most curative management for MTC, optimal outcomes depend on early diagnosis, suitable patient selection, and meticulous planning of surgical treatment. This review discusses recent trends in the incidence of MTC, care model organization, and advances in surgical management to provide insight into the challenges and opportunities in this evolving field.

Trends in Incidence

Rising Detection Rates

The incidence of MTC has been seen to increase slowly over the last decades, attributed to better diagnostic abilities and genetic testing for RET mutations in familial cases. Advances in ultrasonography, fine-needle aspiration biopsy (FNAB), and calcitonin measurement have improved early detection.

Genetic Predisposition and Screening

About 25% of MTC cases are hereditary, associated with RET mutations in MEN2 syndromes. Prophylactic thyroidectomy based on genetic risk stratification has contributed to reducing advanced-stage disease in hereditary cases.

Impact of Population-Based Screening

The introduction of population-based screening programs in high-risk groups has led to earlier diagnosis and a shift toward detecting smaller, localized tumors. However, sporadic cases of MTC often present at more advanced stages, underscoring the need for broader awareness and earlier intervention strategies.

Organization of Care

Multidisciplinary Teams

The management of MTC has increasingly relied on centralized care models, involving multidisciplinary teams of endocrinologists, oncologists, surgeons, and genetic counselors. This approach enables comprehensive risk assessment, personalized treatment planning, and integration of emerging therapies.

Centralization of Expertise

The centers provide advanced diagnostic modalities, such as genetic testing and high-resolution imaging, with evidence-based surgical and systemic treatment protocols under the umbrella of centralized centers of expertise in thyroid cancer.

Disparities in Access

Despite advances, disparities in access to specialized care persist, particularly in low- and middle-income countries. Addressing these disparities through telemedicine, outreach programs, and capacity-building initiatives is crucial for equitable care delivery.

Surgical Management of MTC

Total Thyroidectomy: The Cornerstone

Total thyroidectomy is the primary surgical intervention for MTC, aiming to achieve complete resection of the primary tumor and minimize recurrence risk. In hereditary MTC, prophylactic thyroidectomy timing is guided by RET mutation risk stratification.

Lymph Node Management

Meticulous lymph node dissection is critical due to the high propensity of MTC for lymphatic spread. Central compartment lymph node dissection is routinely performed, with lateral neck dissection indicated for clinically or radiologically involved nodes.

Advances in Surgical Techniques

Innovations such as intraoperative neural monitoring and fluorescence imaging have improved surgical precision, reducing complications such as recurrent laryngeal nerve injury and hypoparathyroidism.

Minimally Invasive and Robotic Approaches

Minimally invasive and robotic-assisted thyroidectomy techniques are emerging as viable options for selected MTC cases, offering reduced morbidity and enhanced cosmetic outcomes.

Literature Review

Molecular Insights and Implications

The discovery of RET mutations has not only refined the diagnostic criteria for hereditary MTC but also informed targeted therapies. RET inhibitors, such as selpercatinib and pralsetinib, have demonstrated efficacy in metastatic and advanced MTC, offering new hope for patients with limited options.

Impact of Biomarkers

Calcitonin and carcinoembryonic antigen (CEA) remain invaluable biomarkers for diagnosing, staging, and monitoring MTC. Recent studies highlight the potential of novel biomarkers, such as circulating tumor DNA (ctDNA), in guiding treatment decisions and detecting early recurrence.

Outcomes of Surgical Interventions

Meta-analyses of surgical outcomes underscore the importance of early and complete resection in improving disease-free survival. Studies comparing prophylactic versus therapeutic thyroidectomy in hereditary MTC reveal significant benefits of early intervention in preventing advanced disease.

Challenges and Disadvantages

Late Diagnosis in Sporadic Cases

While hereditary MTC benefits from genetic screening, sporadic cases often present with advanced disease due to nonspecific symptoms and lack of routine screening in the general population.

Surgical Morbidity

Complications such as hypocalcemia, recurrent laryngeal nerve injury, and permanent hypoparathyroidism remain concerns in extensive thyroid and lymph node surgeries.

Resistance to Systemic Therapies

Despite the promise of RET inhibitors, resistance mechanisms, and adverse effects pose challenges in their long-term use. Multimodal strategies combining surgery and systemic therapies are under investigation to overcome these limitations.

Disparities in Care

Geographical and economic barriers to specialized care result in delayed diagnosis and suboptimal management in underserved populations.

Future Directions

Integration of AI and Machine Learning

AI-driven algorithms are being developed to improve risk prediction, tumor characterization, and surgical planning. Machine learning models analyzing imaging and biomarker data could enhance early detection and personalized treatment strategies.

Precision Medicine Approaches

Advances in genomics and molecular profiling will enable more precise risk stratification and therapeutic targeting, minimizing overtreatment and optimizing outcomes.

Expanding Access to Care

Global initiatives to expand access to genetic testing, telemedicine consultations, and capacity-building programs can bridge gaps in care delivery for MTC patients worldwide.

Novel Therapies and Trials

Ongoing clinical trials are evaluating next-generation RET inhibitors, combination therapies, and immunotherapeutic approaches, aiming to improve outcomes for metastatic and refractory MTC.

Conclusion

The evolving trends in incidence, organization of care, and surgical management of medullary thyroid cancer emphasize the need to combine molecular advances, multidisciplinary collaboration, and innovative surgical techniques. Therefore, despite all these evolutions and increasing trends in incidences with better organization of care, late diagnosis, and resistance to systemic therapies pose challenges. By embracing precision medicine, increasing global access to specialized care, and promoting research into new therapies, MTC management continues to make headway, assuming better outcomes and quality of life for patients across the globe.

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