Effect of Primary Tumor Resection on Survival Outcomes for Stage IV Medullary Thyroid Carcinoma

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Article:
    • Liu C-Q, Shen C-K, Du Y-X, et al. Survival outcome and optimal candidates of primary tumor resection for patients with metastatic medullary thyroid cancer. J Clin Endocrinol Metab 2024;109(11):2979-2985; doi: 10.1210/clinem/dgae214. PMID: 38570918.
  • Background:
    • Medullary thyroid cancer (MTC):
      • Is a rare malignancy with high metastatic potential
    • Distant metastases are present in 10% of patients at diagnosis and portend an overall poor prognosis:
      • With 10-year survival rates below 50%
    • Complete surgical excision of the primary tumor, including lymph nodes:
      • Is the only curative strategy for localized MTC:
        • However, limited data exist on the potential benefit of primary tumor resection (PTR) on survival in people with distant metastases at diagnosis
    • This study aimed to leverage a population-based registry to:
      • Assess the prognostic significant of site-specific metastasis and number of metastases
      • Evaluate survival outcomes of patients with metastatic MTC who underwent PTR
      • Identify the optimal candidates for PTR in patients with metastatic MTC
  • Methods:
    • This study analyzed the Surveillance, Epidemiology, and End Results (SEER) database:
      • Between 2010 and 2020 for patients with MTC who had distant metastasis at diagnosis
    • Key variables extracted included demographics (age, gender), tumor characteristics (grade, size, metastatic site), and treatment details (PTR, neck dissection, radiation, and chemotherapy)
    • The SEER database exclusively provides data on five metastatic sites: lung, bone, liver, brain, and distant lymph nodes
    • Patients were divided into PTR and non-PTR groups, and survival outcomes (overall survival [OS] and cancer-specific survival [CSS]) were analyzed using Kaplan–Meier curves and log-rank tests
    • Cox regression models were used to identify independent prognostic factors
  • Results:
    • The most common metastatic sites in the 186 patients (median age, 56 years; range, 8 to 89) included in this study were:
      • Bone (45.7%)
      • Liver (39.8%)
      • Lung (36.6%)
    • Brain metastasis (n = 10, 5.4%):
      • Was associated with significantly poorer:
        • OS (P = 0.0007) and CSS (P = 0.0013):
          • As compared to other metastatic sites
    • Kaplan–Meier analyses found that patients with more metastatic sites had worse CSS (P= 0.026):
      • However, the number of metastases was not a significant predictor of survival on univariable and multivariable Cox regression
    • More than half of the cohort (n = 106, 56.5%) underwent PTR
    • The PTR group had approximately one-third the hazard of overall mortality (HR, 0.29; 95% CI, 0.13–0.64; P = 0.002) and cancer-specific mortality (HR, 0.38; 95% CI, 0.16–0.94; P = 0.036) than the non-PTR group
    • In subgroup analyses by metastatic site:
      • PTR was associated with better survival in patients with metastasis to the lung, bone, liver, or distant lymph node (DLN):
        • But showed no significant difference for those with brain metastasis
      • In patients who had one or two organs with metastasis:
        • PTR was associated with improved OS (P< 0.01) and CSS (P < 0.05):
          • Whereas no survival difference was observed in those who had more than two organs with metastasis
  • Conclusions:
    • In patients with MTC and distant metastasis at diagnosis:
      • Patients who underwent PTR had better OS and CSS than those who did not
    • No difference in survival with PTR was observed in the small subgroup with:
      • Brain metastases, who also had a worse prognosis than those with other metastatic sites
    • The authors conclude that PTR may confer survival benefits in metastatic MTC:
      • Optimal candidates are those with metastases in one or two organs and those without brain metastases
  • Summary:
    • For patients with extensive regional or metastatic MTC:
      • For whom the goals of care are palliative:
        • The 2015 American Thyroid Association (ATA) guidelines recommend a personalized approach:
          • With consideration of neck surgery, radiation and systemic therapies
    • PTR for patients with distant metastatic MTC is often performed for local control, including with palliative intent:
      • Given the high mortality and morbidity associated with airway or neck invasion
    • Tumor debulking:
      • Can also offer reduction in calcitonin level to improve rates of chronic diarrhea:
        • However, this contrasts with the traditional treatment of other stage IV neoplasms and has to date lacked randomized prospective data
    • Using SEER data between 2010 and 2020, this study showed that patients who underwent PTR had better survival outcomes than those who did not
    • These findings are largely consistent with an earlier analysis of the SEER database capturing cases between 1998 and 2015
    • A key limitation of this registry-based study is the absence of data on performance status, a putative risk factor for survival and an important predictor of PTR eligibility
    • Given the retrospective design and lack of adjustment for performance status as a confounder, causality between the role of PTR and survival cannot be established
    • Additionally, metastatic MTC varies widely in behavior, from indolent to aggressive
    • Predictors of disease activity such as tumor markers and doubling times of calcitonin and carcinoembryonic antigen were not included in this study owing to registry limitations
    • The multiple subgroup analyses that aimed to identify optimal candidates for PTR based on metastatic site and number were also largely underpowered
    • Thus, the authors’ recommendation that PTR should only be considered in those with one or two metastatic organs or those without brain metastases should be interpreted with caution
    • Notably, these data from 2010 to 2020 largely precede the widespread use of multikinase and selective RET inhibitors:
      • Which have changed the therapeutic landscape of MTC, and also may alter the role of PTR
    • Data on RET pathogenic variant status and use of targeted therapies were not captured by the SEER database
    • The role of RET-targeted kinase inhibitors as neoadjuvant therapy is under active investigation with an ongoing phase II trial on the use of selpercatinib before surgery for RET-altered thyroid cancers
    • Although we cannot infer a survival benefit from PTR from these retrospective registry-based studies:
      • These data reassure clinicians to continue recommending PTR in suitable candidates with MTC and distant metastases
      • Furthermore, although quality of life was not examined in this article, the importance of lowering calcitonin cannot be overstated, as high calcitonin can confer significant morbidity through hormone-mediated chronic diarrhea
    • As targeted molecular therapy becomes more prevalent, further data will be required to inform the evolving role of PTR in metastatic MTC management
Unknown's avatar

Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

Leave a comment