*1.5.2 Role of USG and computer tomography in the detection of nodal metastasis*

USG and computed tomography (CT) are commonly used for preoperative detection of nodal metastasis in DTC. However, it is important to determine which individual imaging modality should be chosen alone or in combination. In general, USG is cheap, easily accessible, and allows diagnostic real-time fine needle aspiration cytology or biopsy. Conversely, CT is a standardized technique that is non-operatordependent, provides greater anatomical details, and allows accurate evaluation of

the retropharyngeal, retrosternal, and mediastinal areas not accessible by USG [38]. In addition, CT can be useful in evaluating extra-thyroidal tumor extension, better detecting multi-level nodal involvement or presence of extranodal extension, and better assessing the anatomical relationship with adjacent critical structures. Hence, both USG and CT are complementary modalities for the investigation of nodal metastasis.

In a retrospective study, USG had an overall sensitivity of 51% and specificity of 92% in preoperative detection of nodal metastasis [39]. The performance of CT was statistically similar at a sensitivity of 62% and a specificity of 93%. Combined USG/ CT only improved sensitivity in patients with lateral compartment nodal disease and in patients with nodal involvement of more than one level. These findings were replicated and summarized in a meta-analysis of 1691 patients [40].

Based on the above evidence, the American Thyroid Association (ATA) recommends USG as the first line modality in all DTC while additional CT is considered in larger cancers for patients with higher chance of nodal metastasis and extrathyroidal spread [41]. Scenarios, where CT would be particularly useful, include patients presenting with pressure symptoms arising from thyroid mass, hoarseness of voice, clinically fixative thyroid mass (cT4), and retrosternal thyroid extension incompletely assessed by USG, and patients with palpable bulky lymph nodes.

#### *1.5.3 Role of positron emission tomography in the evaluation of nodal metastasis*

Recently there is an increasing interest in the role of positron emission tomography (PET) with 18-fluoro-2-deoxy-d-glucose (18FDG) for evaluating nodal metastasis in DTC. In the last two decades, 18FDG-PET has emerged as a growing method for detecting DTC recurrences, particularly in non-iodine avid diseases such as Hürthle cell carcinomas [42, 43]. In a multicentre study, the sensitivity of 18FDG-PET to detect recurrent disease was shown to be greater than 131I whole body scan (WBS) [44]. However, PET provides low spatial resolution and suboptimal anatomical details. Co-registering PET with CT overcomes this limitation such that 18FDG -PET/CT has become an adjunctive tool in the detection of recurrent DTC, particularly in patients with elevated serum thyroglobulin and negative WBS.

The potential role of PET/CT in the detection of nodal metastasis prior to initial surgery has growing research attention. Jeong et al. evaluated the utility of preoperative PET/CT in their retrospective cohort and reported that PET/CT had a diagnostic accuracy of 92.3% with a sensitivity of 30% and a specificity of 96% in detecting nodal metastasis which was comparable to USG and CT [45]. However, PET/CT did not provide any superior diagnostic accuracy when indirectly compared with USG and CT in a network meta-analysis [46]. Further high-quality direct comparative studies are required to further elucidate the role of PET/CT particularly in the preoperative assessment for nodal metastasis. Current evidence only supports the role of PET/CT in the postoperative detection of recurrent DTC.

**Table 2** summarizes the diagnostic performance of various radiological modalities in the preoperative detection of cervical nodal metastasis across all cervical levels.

#### **1.6 Prognostic implication of nodal metastasis**

It is important to understand how nodal metastasis in DTC affect prognosis in order to justify its preoperative detection and neck dissection. Although survival


#### **Table 2.**

*Imaging modalities in preoperative detection of cervical nodal metastasis.*

of DTC is generally very good, certain specific populations may suffer from greater chances of recurrence and mortality.

#### *1.6.1 Lymph node metastasis and cancer-specific survival*

Regional nodal metastasis had been implicated as a prognostic factor for survival in earlier studies involving large retrospective cohorts [47–49]. For example, Podnos et al. demonstrated a significantly lower overall survival at 14 years (79% vs. 82%) for node-positive patients in their cohort of 9904 patients. However, these studies have been challenged by newer reports that nodal metastasis only adversely affected cancerspecific survival in a subset of patients >45 years of age but not in those <45 years [50].

#### *1.6.2 Lymph node metastasis and disease recurrence*

Regional nodal metastasis also had been implicated as a predictor of disease recurrence. Macroscopic lymph node involvement, i.e. clinically palpable or radiologically detectible metastatic lymph node, is associated with a high rate of local recurrence (10–42 percent) [51]. Furthermore, patients with >5 positive lymph nodes, higher lymph node ratio, and the presence of extranodal extension were associated with even higher risks of local disease recurrence [51, 52]. However, the association of microscopic (radiologically undetectable and nonpalpable) nodal disease and recurrence was not well demonstrated [53–56]. A randomized controlled trial of clinically node negative (cN0) patients showed that microscopic nodal disease detected by prophylactic neck dissection did not affect disease-free survival [57].

#### *1.6.3 Lymph node metastasis in staging systems*

Based on how nodal metastasis affects survival and recurrence, the presence of nodal metastasis upstages patients over the age of 45 years from American Joint Committee on Cancers (AJCC 6th and 7th edition) from stage I to stage III disease [58]. Similarly, the proposed modifications of the American Thyroid Association risk stratification system classified <5 microscopic nodal metastasis as a component of low-risk disease, macroscopic nodal metastasis or >5 microscopic nodal metastasis as intermediate-risk disease, and any nodal metastasis > = 3 cm in greatest dimension as high-risk disease [59]. These staging systems influence the degree of postoperative thyroid-stimulating hormone suppression therapy and determine whether radioiodine ablation (RAI) should be given. Hence, accurate nodal status has an important clinical significance.
