Total or partial thyroidectomy for low-risk differentiated thyroid cancer: that is the question!| ACTA Otorhinolaryngologica Italica

Dear Editor,

We greatly appreciated the critical comparison between the 2015 American Thyroid Association Guidelines (ATA-GL) and the 2018 joint Italian Consensus (IC) on medical and surgical management of thyroid nodules, which Arrigoni and colleagues have recently published in this Journal ¹. The Authors give a bird’s eye view of the current evidence-based recommendations for a commonly encountered condition, yet we believe that some points of their analysis need further insight.

For instance, a practical dilemma that every thyroid/head and neck surgeon has to face in their clinical practice is the choice between total thyroidectomy (TT) versus loboisthmectomy (LI) for low-risk differentiated thyroid cancer (DTC) ^2,3. The incidence of DTC has strikingly increased in the last decades (about 2-3 fold in the United States and in Europe, but nearly 10-fold higher in South Korea), which is mainly attributed to overdiagnosis. In addition, almost 70% of these tumors have a maximum diameter of less than 2 cm (cT1, according to the VIII Edition of the TNM staging system), and with no suspicious lymph nodes at neck ultrasound, i.e. with a low risk of nodal or distant metastases and with a near-zero cancer-specific mortality ⁴. The LI procedure obviously grants lower treatment-related risks (permanent hypoparathyroidism, laryngeal nerve injury, or lifelong thyroid hormone supplementation), and it has inferior operative time and costs. However, such a procedure is recommended only for cT1aN0 DTC, a situation that should represent a rare occurrence since the ATA-GL recommend against fine-needle aspiration of nodules < 1 cm, whatever the radiological pattern identified ².

The problem arises for cN0 DTC of 1-4 cm (sometimes referred to as “macro-carcinomas”) and without gross extrathyroidal extension: in such cases, patients must incur into a second-stage completion surgery in case of adverse pathological features (aggressive variants, vascular invasion, presence of genetic mutations, etc.) ^2,3. Both ATA-GL and IC consider TT to be a reasonable choice in older patients (> 45 years), contralateral nodules, compressive symptoms, personal history of radiation therapy to the neck, and familial DTC ^2,3. A recent retrospective large single-center series has confirmed this dichotomy: LI yielded an event-free survival of 87.5% versus 95% for the TT group, but, despite an adequate mean follow-up time of 79.9 months, this difference was non-significant (p = 0.067) ⁵. However, only about 15% of the low-risk compared to 50% of the intermediate-risk microcarcinomas treated by LI ultimately needed additional treatments, such as further surgery or radiometabolic therapy ⁵.

In this regard, the recently published ESTIMABL2 trial has just strengthened the evidence for avoiding postoperative radioiodine (with its costs and side effects such as lacrimal discomfort) in low-risk DTC cases. This prospective multicenter French study involved 730 patients receiving TT and its main endpoint was occurrence of any functional (e.g., foci of uptake), structural (nodules detected by ultrasound), or biologic (increase in thyroglobulin) events ⁶. Over 95% of patients were event-free after three years of follow-up and without any significant difference between those receiving post-operative radioiodine and those who were simply followed-up. Notably, less than 50% of patients had multifocal nodules, while T1a cases constituted around 20% of the cohort.

Another understudied issue, and which is often overlooked by guidelines, is a clear definition of what are the “patients’ preferences” regarding the extent of surgery. For example, in a recent well-designed study where the benefit-risk trade-offs of TT versus LI were weighted against each other, the risk of cancer recurrence impacted participants’ preference the most, while TT was the preferred option unless the chance of needing completion surgery following LI is 30% or less ⁷. The latter procedure has the same complication rates of TT in experienced hands and, when thorough preoperative evaluation is conducted, it is required only in less than 10% of cases ⁸. Another factor strongly influencing this decision is the term (“cancer” versus “tumour” versus “nodule”) used by the head and neck surgeon. For papillary microcarcinomas (< 1 cm), we now have sound evidence supporting not only LI but also an active surveillance strategy approach ⁹. Knowing that only around 5.3% of these tumors increase in size by around 3 mm after 5 years of follow-up, that only 1.6% of patients develop nodal metastases, and that foci of DTC are incidentally found in 11.2% (CI 6.7-16.1%) of autopsies, should not we change our mind when we deal with DTC patients? Furthermore, some subcategories of DTC such as the recently characterised noninvasive follicular thyroid neoplasm with papillary-like nuclear (NIFTP) features do not even deserve the words “cancer” or “malignancy”. Unfortunately, accurate preoperative identification of NIFTP remains impossible at present because it remains a purely histopathological diagnosis ¹⁰.

In conclusion, the Authors are to be praised for their efforts to synthesise two of the currently available guidelines on thyroid nodules and thyroid cancer. We still have many difficulties in the identification of the perfect candidate for LI or for an active surveillance strategy, nor have we fully appreciated the role of the patient and their caregivers in the decision-making process. However, it looks obvious that without strong expertise in surgery, ultrasonography, and cytopathology (i.e., managing these patients in high-volume referral centers), the Hamletic doubt between TT and LI does not even arise. The Authors’ suggestion to draft a future position paper on the subject from the Italian Society of Otorhinolaryngology Head and Neck Surgery is therefore warmly welcome, and we are confident such a project will be successful as long as we keep a holistic and evidence-based view on DTC management (Fig. 1).

Conflict of interest statement

The authors declare no conflict of interest.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contributions

MGR and CM discussed the paper, LGL wrote the paper.

Figures and tables

Figure 1.Practical issues to be evaluated when selecting the ideal operative approach for low-risk differentiated thyroid cancer.

References

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