Update on Differentiated Thyroid Cancer Staging

Differentiated thyroid carcinoma (DTC) is the most common endocrine cancer. Particularly the incidence of small clinically indolent tumors has been increasing significantly during the last decades because of increased diagnostic scrutiny, while the DTC-related mortality remained unchanged. In light of the increased awareness of the significant risk of detecting clinically indolent tumors and the potential harm and burden associated with overly diagnosis and the treatment, the approach towards management of DTC recently underwent a critical appraisal. The focus lays on reducing the unnecessary burden for patients with very low risk DTC and the correct identification of those who require treatment that is more intensive and/or follow-up. Management of DTC includes a range of different modalities, making multidisciplinary collaboration expedient. In this review, we elaborate on the recent developments in diagnosis, staging and management of DTC with specific focus on the more individualized risk assessment-based approach.

Evaluar la adecuación de la supresión de TSH (tsTSH) al diagnóstico y en la última visita de seguimiento.

Estudio observacional retrospectivo en aquellos pacientes en seguimiento por CDT en un hospital de tercer nivel.

Se evaluaron 216 pacientes (79,2% mujeres), edad media 59,0±13,1 años y un seguimiento medio de 6,9±4,3 años. Un 88,4% fueron carcinomas papilares.

Al diagnóstico, el 69,2% presentaban un riesgo bajo de recurrencia (RR) vs. 13,6% de RR elevado. La estadificación dinámica del riesgo (EDR) clasificó a los pacientes, inicialmente y en la última visita, como respuesta excelente (RE) en un 60% y un 70,7%, respectivamente.

Aquellos pacientes con RE en el primer y último control de seguimiento, mantuvieron tsTSH en un 30,7 y 16,3% de los casos, respectivamente (p < 0,001).

Los factores asociados a mantener la tsTSH en la última visita de control fueron la menor edad, mayor RR al diagnóstico, la EDR en el seguimiento, la presencia de multifocalidad e invasión vascular (p < 0,05).

En un modelo de regresión logística adoptando la tsTSH en el seguimiento como variable dependiente, exclusivamente la edad (β = -0,062; p < 0,001), el RR al diagnóstico (β = 1.074; p< 0,05) y la EDR en el seguimiento (β = 1.237; p < 0,05) mantuvieron la significación estadística.

A pesar de las recomendaciones actuales, un 30,7% de los pacientes con bajo RR y RE inicial se encuentran bajo tsTSH. Este porcentaje se redujo al 16,3% en RE tras un seguimiento medio de 6,9 años. La edad, el RR inicial y la EDR durante el seguimiento se relacionaron con mantener la tsTSH.

To evaluate the adequacy of TSH suppression therapy (TSHst) at the first disease assessment and the last follow-up visit.

Retrospective observational study of those patients under follow-up of DTC in a reference hospital.

216 patients (79.2% women) were evaluated, with a mean age 59.0±13.1 years-old and a mean follow-up of 6.9±4.3 years. 88.4% were papillary carcinomas.

At diagnosis, 69.2% had a low risk of recurrence (RR) compared to 13.6% with a high RR. Dynamic risk stratification (DRS) classified patients at first disease assessment and the last visit as excellent response (ER) in 60.0% and 70.7%, respectively.

Those patients with ER in the first and last follow-up control maintained TSHst in 30.7% and 16.3% of the cases, respectively (p < 0.001).

The factors associated with maintaining TSHst at the last control were younger age, higher RR at diagnosis, DRE at follow-up, presence of multifocality and histological vascular invasion (p < 0.05).

In a logistic regression analysis adopting tsTSH at follow-up as the dependent variable, exclusively age (β = -0.062; p < 0.001), RR at diagnosis (β = 1 074; p < 0.05) and EDR during follow-up (β =1 237; p < 0.05) maintained statistical significance.

Despite the current recommendations, 30.7% of patients with low RR and initial ER are under TSHst. This percentage reduced to 16.3% in those patients with ER after a mean follow-up of 6.9 years. Age, baseline RR, and DRE during follow-up were associated to maintaining tsTSH.

No study assessed the behaviour/epidemiology of differentiated thyroid cancer (DTC) among Filipinos in the Middle East/north Africa; or compared such behaviour with Filipino DTC patients in and outside the Philippines.

Retrospective review of all adult Filipinos with DTC diagnosed between 2015 and 2020 at our institution [papillary TC (PTC, n = 110); follicular TC (FTC, n = 4)]. Chi-square or t-test compared the frequency, demography, history, ultrasound, laboratory and histopathology of PTC vs FTC; and compared the epidemiology of DTC among Filipinos in Qatar vs Canada (1 study) vs the Philippines (3 studies).

DTC frequency was ≈43.84 cases/100,000 Filipinos in Qatar. Males had more aggressive disease in terms of lymphovascular invasion, number of nodules, stage IV disease and metastases. PTC and FTC were similar, but more PTC patients presented with solid tumors and higher number of involved lymph nodes. DTC behaviour among Filipinos in Qatar vs Canada was fairly homogenous. Conversely, DTC among Filipinos in Qatar vs Philippines exhibited many dissimilarities: Qatar had significantly younger patients, less hyperthyroid/thyrotoxicity symptoms and neck swelling at presentation, fewer solid nodules, micro-calcifications, and multi-nodular disease; smaller tumors; more stage I and less stage IV disease; and no distant metastasis (P 0.01 to < 0.0001).

DTC epidemiology among Filipinos in Qatar and Canada was fairly homogenous. Conversely, DTC in Qatar vs the Philippines was dissimilar. DTC among Filipinos in Qatar has presentations that could be misinterpreted as non-suspicious. This warrants additional practices for earlier detection among Filipinos.

Interleukin (IL)-17A has a dual role in tumor immunity, promotes anti-tumor responses and facilitates angiogenesis by interacting with IL-17 receptor A (IL-17RA). Although IL-17A has been associated with the pathogenesis of papillary thyroid carcinoma (PTC), the nucleotide variability at the IL17A and IL17RA genes is still poorly characterized.

To assess the contribution of the IL17A (-197 G >A, rs2275913) and IL17RA (-947 A >G, rs4819554) single nucleotide polymorphisms (SNP) on the development and progression of PTC and on IL-17 plasma levels.

We studied 188 PTC patients and 170 healthy controls. SNPs were identified using PCR-amplified DNA and restriction fragment length polymorphism (RFLP) techniques. Plasma levels of IL-17A was evaluated in 83 PTC patients using ELISA. Statistical analyses were performed to evaluate the associations between SNPs and clinicohistopathological features of PTC and IL-17A levels.

No significant difference was observed regarding the allele and genotype distributions of both SNPs between PTC patients and controls. The IL17A GA was associated with poor biochemical and structural incomplete response to therapy, whereas no influence over the IL-17A expression was observed. The IL17RA AG was significantly associated with small-sized tumors, initial tumor stage at diagnosis and better response to therapy.

The IL17A SNP may predict an aggressive manifestation of PTC, whereas the IL17RA SNP was associated with a more favorable clinical outcome.