A number of characteristics of the tumor will affect the prognosis of the tumor. Some of the more important factors include tissue type, primary tumor size, extraglandular invasion, vascular infiltration, BRAF mutations, and distant metastases.
(1) Tissue type: PTC patients have an overall good survival rate, but tumor mortality rates vary considerably between specific subtypes. Among them, the hypercellular, shoe-peg, columnar cell and solid types are the aggressive subtypes.
FTC is typically characterized by isolated tumors with an envelope and is more aggressive than PTC. fTC usually has microfollicular structures and is diagnosed as cancer due to infiltration of follicular cells into the envelope or blood vessels, and those infiltrating into the blood vessels have a worse prognosis than those infiltrating the envelope. Highly invasive FTC is uncommon and is often seen to invade surrounding tissues and blood vessels intraoperatively. Approximately 80% of highly invasive FTCs develop distant metastases, which can lead to death in approximately 20% of patients within a few years of diagnosis. The poor prognosis is closely related to the patient’s age at diagnosis, high tumor stage, and large tumor size; PTC has a similar prognosis to FTC, and both have a better prognosis if the tumor is confined to the thyroid gland, is less than 1 cm in diameter, or is minimally metastatic. If distant metastasis and high invasion occur, the prognosis is poor.
(2) Primary tumor size: papillary carcinoma <1cm is called microscopic carcinoma, which is usually detected by physical examination and has almost 0 lethality rate and low risk of recurrence. However, microscopic cancer is not always a tumor with low risk of recurrence. For example, about 20% of multifocal microscopic cancers have cervical lymph node metastasis and also have the risk of distant metastasis.
The size of the primary tumor is associated with prognosis and mortality. It has been shown that DTC with primary tumors <1.5 cm in size are less likely to develop distant metastases, while larger tumors (>1.5 cm) have a recurrence rate of approximately 33% within 30 years. The 30-year mortality rate of DTC with a maximum diameter of <1.5 cm is 0.4%, while that of larger tumors (>1.5 cm) is 7%.
(3) Local invasion: About 10% of DTCs invade surrounding organs/structures, and the local recurrence rate is about twice as high as that of non-invasive tumors. The mortality rate of patients with invasive cancer is also increased, with about 1/3 of patients dying.
(4) Lymph node metastasis: The role of regional lymphatic metastasis on prognosis is controversial. There is evidence to support that regional lymph node metastasis does not affect recurrence and survival. There is also evidence to support that lymph node metastasis is a high risk factor for local recurrence and cancer-related mortality. There is a correlation between lymphatic metastasis and distant metastasis, especially those with bilateral cervical lymph node metastasis, or extra-peripheral lymph node invasion, or mediastinal lymph node metastasis.
(5) Distant metastasis: For DTC, distant metastasis is a major cause of death. About 10% of PTC and 25% of FTC will have distant metastasis. Distant metastases are found more frequently in patients with eosinophilic adenocarcinoma29 and in those aged >40 years (35%). The most common location of distant metastases is the lung, followed by bone, liver, and brain. Distant metastases make the prognosis worse.