Implications and Management of a Biochemical Incomplete Response in Dynamic Risk Stratification

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • A biochemical incomplete response is defined as:
    • Negative imaging with elevated thyroglobulin (Tg) or anti-Tg antibodies:
      • During follow-up after initial treatment for differentiated thyroid cancer (DTC)
  • This response category reflects persistent biochemical evidence of disease:
    • Without structural correlates
    • The prognosis for patients with a biochemical incomplete response:
      • Is generally favorable but variable:
        • Approximately 30% of patients spontaneously achieve no evidence of disease (NED)
        • An additional 20% achieve NED with further therapy
        • 20% progress to structural disease
          • Disease-specific mortality is rare, occurring in less than 1% of cases
  • Risk Factors and Predictors:
    • Several factors influence the likelihood of a biochemical incomplete response and its progression:
      • BRAFV600E mutation:
        • Is significantly associated with biochemical incomplete response, with studies showing a higher prevalence of this mutation in affected patients
        • This mutation also correlates with an increased risk of progression to structural disease
      • Patients with a biochemical incomplete response have a higher recurrence risk compared to those with an excellent response:
        • But their risk is lower than that of patients with a structural incomplete response
  • Management Strategies:
    • Management of a biochemical incomplete response:
      • Is guided by the trend in Tg or anti-Tg antibody levels and the absence of structural disease
    • Observation with TSH suppression:
      • For patients with stable or declining Tg levels, continued observation with ongoing TSH suppression is recommended:
        • The degree of TSH suppression should be individualized based on the patient’s risk profile and comorbidities
    • Rising Tg or anti-Tg antibody levels:
      • If Tg or anti-Tg antibody levels increase, further evaluation with imaging (e.g., neck ultrasound, cross-sectional imaging, or functional imaging such as RAI SPECT/CT or PET-CT) is warranted
      • Additional therapies, such as radioactive iodine (RAI) therapy, may be considered in select cases:
        • Particularly if Tg levels remain persistently elevated or if there is evidence of iodine-avid disease
    • Additional RAI therapy:
      • While not universally required, additional RAI therapy may be beneficial in patients with persistent biochemical evidence of disease:
        • Especially if Tg levels are significantly elevated or rising
        • Approximately 20% of patients achieve NED with further RAI therapy
  • Clinical Outcomes and Long-Term Follow-Up:
    • Long-term outcomes for patients with a biochemical incomplete response are generally favorable:
      • Most patients either achieve NED or remain biochemically stable without progression to structural disease
      • Approximately 60% of patients with a biochemical incomplete response have no evidence of disease over long-term follow-up
    • Dynamic risk stratification (DRS) allows for individualized follow-up and management adjustments based on evolving risk
    • This approach ensures that patients with stable disease are not overtreated, while those with evidence of progression receive timely intervention
  • Gaps in Evidence:
    • Despite the utility of DRS, there are gaps in the evidence regarding the management of biochemical incomplete response:
      • Limited prospective studies:
        • Most data on biochemical incomplete response are derived from retrospective studies
        • Prospective studies are needed to validate management strategies, particularly in patients treated without RAI

          – Patients treated without RAI:
          • The interpretation of Tg levels and the utility of DRS in patients treated with lobectomy or total thyroidectomy without RAI remain less well-defined, necessitating further research
  • In summary:
    • A biochemical incomplete response in DRS is associated with a generally favorable prognosis, though a subset of patients may progress to structural disease
    • Management involves close monitoring, TSH suppression, and selective use of additional therapies, with long-term outcomes guided by dynamic risk stratification
  • References:
Rodrigo Arrangoiz, MD (Oncology Surgeon)
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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.

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