Tratamiento Sistémico del Cáncer Diferenciado de Tiroides Refractario a Radioyodo: Indicaciones Actuales y Perspectivas de Futuro

Tratamiento Sistémico del Cáncer Diferenciado de Tiroides Refractario a Radioyodo: Indicaciones Actuales y Perspectivas de Futuro

Systemic Treatment of Radioiodine-Refractory Differentiated Thyroid Cancer: Current Indications and Future Perspectives

Tamara Díaz Vico*/***, Irene Grao Torrente*, María Dolores Picardo Gomendio*, Brezo Martínez-Amores Martínez**/***,
Manuel Durán Poveda*/***

* Unidad de Cirugía Endocrina. Servicio de Cirugía General y del Aparato Digestivo.
     Hospital Universitario Rey Juan Carlos, Móstoles, Madrid, España
**  Servicio de Oncología Médica,
      Hospital Universitario Rey Juan Carlos, Madrid, España
*** Departamento de Especialidades Médicas y Salud Pública,
      Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, España

DOI: https://doi.org/10.14679/5174

Resumen:

Los papilomas escamosos esofágicos son tumores benignos poco frecuentes, representando menos del 2% de los tumores benignos del esófago y con una prevalencia creciente. Aparecen principalmente en personas alrededor de los 50 años, con una leve predominancia femenina, y se localizan mayormente en el tercio medio e inferior del esófago. Su desarrollo está asociado a inflamación crónica por causas químicas o infecciosas, como la enfermedad por reflujo gastroesofágico (ERGE), esofagitis infecciosa (virus del herpes simple o virus del papiloma humano), ingesta de sustancias cáusticas, entre otras. Aunque el Virus del Papiloma Humano (VPH) está relacionado con ciertos cánceres, su rol en el carcinoma escamoso esofágico es incierto y no se ha demostrado transformación maligna directa.
Clínicamente, estos papilomas suelen ser asintomáticos y se detectan incidentalmente en endoscopias, pero pueden causar disfagia, odinofagia o hemorragias en casos inflamatorios extensos. La resección endoscópica suele ser curativa, aunque hay reportes raros de progresión a carcinoma en lesiones grandes o de larga evolución.
Presentamos el caso de una mujer de 62 años con antecedentes de disfagia de larga evolución, esofagitis herpética y ERGE, que desarrolló un papiloma esofágico gigante que ocupaba la mitad de la luz esofágica. Tras intentos fallidos de resección endoscópica, fue intervenida quirúrgicamente. Durante la cirugía se diagnosticó de carcinoma escamoso con infiltración local importante. Posteriormente recibió quimioterapia adyuvante, pero presentó progresión loco-regional de la enfermedad.
Palabras Clave: cáncer de tiroides, radioyodo-refractario, terapia sistémica, inhibidores multiquinasa, toxicidad, terapias dirigidas.

Abstract:

Radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) represents a rare but clinically challenging condition, as it significantly worsens prognosis and alters therapeutic strategies. While most patients with differentiated thyroid carcinoma can be managed with surgery and radioiodine ablation, up to 15% develop refractory disease, defined by lack of iodine uptake or disease progression after adequate cumulative doses. The natural history of RAI-R DTC is heterogeneous: some patients remain stable for years and can be monitored under active surveillance, whereas others experience rapid progression, symptomatic disease, or involvement of critical organs, requiring systemic therapy.
Multikinase inhibitors (lenvatinib and sorafenib) are the current first-line standard of care, with proven benefits in progression-free survival in pivotal phase III trials (SELECT and DECISION). Cabozantinib has emerged as a valuable second-line option after VEGFR-targeted therapy failure (COSMIC-311). Moreover, the identification of actionable molecular alterations has enabled the use of selective targeted therapies, such as RET and NTRK inhibitors, which provide high response rates in selected patients. Immunotherapy, particularly when combined with antiangiogenic agents, is an evolving therapeutic strategy under clinical evaluation with encouraging results.
Systemic therapies are associated with frequent and sometimes severe adverse events —including hypertension, diarrhea, weight loss, and hand-foot skin reaction— that require proactive monitoring and supportive care. Multidisciplinary teams play a crucial role in optimizing treatment selection, toxicity management, and patient counseling. The decision to initiate systemic therapy must be individualized, considering tumor burden, rate of progression, clinical symptoms, and patient expectations, in line with ATA, ESMO and NCCN recommendations.
Key words: thyroid cancer, radioiodine-refractory, systemic therapy, multikinase inhibitors, targeted therapies, toxicity.

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