INTRODUCTION

Thyroid cancer is the most frequent neoplasm of the endocrine system ¹. According to the histological type it can be categorized into differentiated, medullary and anaplastic types ¹. Differentiated thyroid cancer accounts for 90% of all cases and includes papillary and follicular types ².

According to the GLOBOCAN study, which compiled thyroid cancer registries from 185 countries, by the year 2020, the overall incidence was higher in women than in men (10.1 cases vs. 3.1 cases per 100,000 population-years) ³; as was mortality (0.5 deaths per 100,000 population in women and 0.3 deaths per 100,000 population in men) ³. In Peru, an incidence of 6.3 cases per 100,000 population-years was estimated by 2022, ranking tenth among all cancers in general and a mortality of 0.9 deaths per 100,000 population ⁴.

This is due to the increase in the incidence of thyroid cancer worldwide, possibly because of the detection of small and low-risk tumors as a consequence of increased surveillance, but also due to the presence of some risk factors, such as exposure to environmental or therapeutic ionizing radiation, family history and obesity ². Treatment in adults is early and timely, resulting in greater medium and long-term survival. Survival of differentiated thyroid cancer is greater than 95% at five years ⁵, and up to 15 years ⁶; however, there may be persistence or recurrence of the cancer during follow-up, which generates intensive surveillance and other treatment options ⁷.

There are studies of this type of cancer in Peru that are limited to the description of this neoplasm at diagnosis ^8-10, leaving a gap in the evolution and survival of patients, which could have relevance particularly for those with recurrence of the disease, advanced stage or metastasis. Due to the increasing incidence of this neoplasm, we decided to conduct this study with the aim of describing the characteristics of patients with differentiated thyroid cancer and survival in a hospital in Cusco.

THE STUDY

FINDINGS

Of the 150 patients included in the study, 130 (86.7%) were female and the female/male ratio was 6.5. The mean age at diagnosis was 48.3 (SD: 12.7 years). Regarding clinical characteristics, 39 (26%) had neck pain, 23 (15.3%) dysphagia, 19 (12.7%) dysphonia, 12 (8%) dyspnea and 83 (55.3%) other symptoms not related to thyroid cancer. On physical examination, 46 (30.7%) had unaltered thyroid, 59 (39.3%) thyroid nodule and 45 (30.0%) multinodular goiter. Regarding thyroid function, 92 (61.3%) were euthyroid, 53 (35.3%) had hypothyroidism and five (3.3%) hyperthyroidism. The median primary tumor size was 2.5 cm (interquartile range 1.5 to 3.7), 51 (34%) had extrathyroidal extension, 86 (57.3%) had regional lymph node metastases, 23/128 (18%) had distant metastases and 95 (74.2%) had TNM stage I (eighth edition).

Age at diagnosis was higher in men than in women (56.5 years vs. 47 years, p=0.002). Papillary was the most frequent histologic type in 142 (94.7%) patients and follicular in 8 (5.3%) patients. No significant differences were found between tumor size, extrathyroidal extension, regional lymph node metastasis, distant metastasis and TNM stage (Table 1).

Regarding treatment, 106 (70.7%) had total thyroidectomy, 63 (42%) had neck dissection with lymphadenectomy (31 had modified radical dissection, 22 selective dissection, 20 lateral and 2 posterolateral dissection, and 10 had central dissection). After surgery, 146 (97.3%) had hypothyroidism, 58 (38.7%) had hypoparathyroidism and 23 (15.3%) had recurrent laryngeal nerve injury. One hundred and three (68.7%) patients received radioactive iodine.

The median follow-up time was 4.6 years (ICER 3.5-6.6), it was 4.9 years (IQR: 3.9-6.8) for the group that completed follow-up (alive) and 1.9 years (IQR: 1-2) for those who presented the outcome (deceased).

At the end of follow-up, 15 deaths due to cancer were reported (13 papillary and 2 follicular). Of these, 11 (73.3%) were ≥ 55 years, all had regional lymph node metastases and 12 (85.7%) had distant metastases (Table 2). Of the 13 deceased patients with papillary cancer, all had regional lymph node metastases and 10 distant metastases, and the two deceased patients with follicular cancer also had these features. Of the 133 patients who did not have the outcome (alive), 44 (33.1%) had cancer persistence, 21 (15.8%) had recurrence and 68 (51.1%) had excellent response to treatment.

At 1-year follow-up, the survival rate was 98% (95%CI: 93.8-99.3), at 2 years it was 93% (95%CI: 87.4-96.2), at 3 years it was 90.1% (95%CI: 83.9-94), at 4 years it was 89.3% (95%CI: 82.8-93.4) and at 5 years it was 89.3% (95%CI 82.8-93.4) (Figure 1).

Figure 1 Survival of patients with differentiated thyroid cancer. 

Survival was significantly lower in those with age at diagnosis ≥ 55 years, tumor size > 4cm, extra-thyroidal extension, distant metastasis, and was higher in those with radioactive iodine treatment (Table 2).

DISCUSSION

In our study, differentiated thyroid cancer was more frequent in women with papillary histological type and more than half of the patients required total thyroidectomy and the use of radioactive iodine. Survival at 5 years was 89%, being lower in those with TNM stage IV.

Our study analyzed differentiated thyroid cancer, being papillary thyroid cancer, the most frequent type, in agreement with reports from other countries ^5,6,12. This type of cancer affected women more frequently, as in other studies ^5,6,12. This difference between both sexes can possibly be explained by a greater use of health services by women ¹³, and therefore a greater detection of this cancer in asymptomatic stages when the tumors are small. The hormonal effect of estrogen on thyroid stimulating hormone has also been considered, especially in older women with menopause ¹⁴; however, this is not yet conclusive ¹⁵.

The mean age at diagnosis (48.3 years) was similar to that reported in Ecuador (44.6 years) ¹⁶, Brazil (46.5 years) ⁵, Spain (48.3 years) ⁶ and lower than that reported in Colombia (51.1 years) ¹². These differences may be explained by the cancer detection strategies that have been implemented in each country, such as the use of low-cost imaging techniques that are accessible to the population such as neck ultrasound ^6,16, producing a diagnosis at earlier ages and even when the patient has no symptoms ². We found that 30.7% had no alterations on physical examination and detection was incidental, less than in a study in Ecuador, in which 54.2% had this characteristic ¹⁶. Symptomatic patients at diagnosis tend to present advanced stages of the disease ¹⁷, while asymptomatic patients are those who have thyroid tumor as a finding incidentally during routine studies, which also explains the increase in diagnosis in recent years ^2,18.

In 2016, the TNM staging system for thyroid cancer was updated and one of the important changes was the age cut-off point from 45 to 55 years due to no difference in survival at 10-year follow-up ¹¹. In our study, those with age ≥ 55 years had lower survival, similar to other reports ^5,6. The TNM stage I (74.2%) in our study was similar to that reported in Brazil (74.8%) ⁵ and lower than that reported in Colombia (82.6%) ¹², suggesting that the diagnosis of patients is becoming increasingly frequent in early stages, possibly due to the use of imaging resources, such as ultrasound, as a consequence of greater access to medical care ².

The survival rate at five years was 89.3%, lower than that reported in Brazil, 95.8% ⁵, and in Spain 95.1%, at 5 and 15 years of follow-up respectively ⁶. These differences can be explained by conditions that may predispose patients to mortality, since in Brazil and Spain, distant metastasis was reported in 5.3% and 5.5%, lower than the 18% reported in our study. Distant metastasis is found in advanced stages of cancer, being a factor associated with mortality ^5,6, and the study showed that these patients had lower survival rates, since involvement of other organs such as the lung or bone may predispose to complications during follow-up. Differences between the health systems of each country ^5,6 and the socioeconomic level could also influence survival due to this cancer ¹⁹.

In our study, the patients who used radioactive iodine had greater survival, contrasting with a previous study in Brazil ⁵. This therapy has two functions, the ablation of benign thyroid remnants after total thyroidectomy, in order to properly interpret serum thyroglobulin (useful in follow-up) and as an adjuvant treatment to eliminate cancerous tissue remnants, thus reducing the risk of recurrence and improving survival ²⁰, therefore radioiodine is recommended for patients with regional lymph node metastasis, vascular invasion, extra-thyroidal extension and distant metastasis ⁹.

The prevention, diagnosis and management of cancer is multidisciplinary and requires the participation of all social and governmental actors. In Peru, strategies have been developed to support cancer care, such as the creation of Regional Institutes for Neoplastic Diseases, oncology services and units in hospitals ²¹, implementation and funding of the “Plan Esperanza”, the latter with the aim of reducing the gap in access to oncology services in all regions ²², and therefore, mortality from this and other types of cancer.

One of the strengths of this study is that the median follow-up (4.6 years) was similar to studies with a larger number of participants ^5,6, which shows the results of the management and follow-up of these patients in the long term. There are also limitations, such as the small sample size, the retrospective collection of data and the fact that we used information from a single hospital, so these results could not be extrapolated to other populations. However, these findings are important because they come from a population outside the capital of Peru, so this topic should be further researched in our country with larger populations, multicenter type, with other characteristics that may influence survival and with more complex designs.

In conclusion, in a Peruvian hospital, differentiated thyroid cancer was more frequent in women in its papillary form, and survival was lower than described in other studies. We recommend prospective studies to be carried out, with longer follow-up time in other Peruvian institutions, in order to compare the clinical outcomes of these patients over time.