Total thyroidectomy with or without CND was the recommended/preferred treatment for PTC > 1 cm [8, 9]. However, in 2014, Adam et al. asked a question: should tumour size be an absolute indication for TT? This question arose from an analysis of 61,775 PTC with tumours 1–4 cm in diameter with no clinically high risk features (i.e., ETE, metastases, or aggressive histology), which suggested that the overall survival between patients who underwent TT was no different from that of those who underwent TL [20]. Thus, the ATA (2015) and European Society for Medical Oncology (ESMO; 2019) revised their guidelines with respect to initial management of patients; the recent guideline state that TL is equivalent to TT with respect to PTC > 1–4 cm with no apparent clinically aggressive factors on pre-operative evaluation [5, 21]. Management should also take into account patient preference [4].

It must be acknowledged that the entire risk landscape of PTC is determined after surgery and is based on the final pathology report. Post-operative findings are crucial for patients who would have been eligible for initial TL. Thus, the prevalence of high risk features in those with PTC > 1–4 cm has become an important area of interest; however, several studies included PTC of 1 cm (MPTC) or follicular TC within the analysed groups [12,13,14,15,16,17]. These studies indicated that 30% to nearly 50% of patients have unrecognised pre-operative high risk factors, even though the PTC was identified as low risk initially [12,13,14, 16]. Additionally, the majority of studies showed that the prevalence of I-H risk factors was higher in those with tumours ≥ 2–4 cm [12, 13, 16, 17]. Our findings are in line with these results. Here, we found that risk factors such as vascular invasion, ETE, and LN and DM were significantly more common in those with larger tumours than in those with PTC > 1–2 cm. It is worth noting that we analysed patients with no apparent pre-operative LN metastases who underwent TT with CND. This selection of patients might have impacted our results, which are close to the upper reported frequency of at least one risk factor (i.e., 47%); however, they are concordant with the knowledge that CND identifies more positive LN, and the prevalence of occult central LN metastases rises with increased tumour size [22]. Our study also showed that patients with PTC of > 2–4 cm had almost double the risk of vascular invasion, a well-known risk factor for further metastases, and double and seven times the risk of having LN and DM, than those with smaller tumours of > 1–2 cm.

With respect to tumours of > 1–4 cm, a diameter of 2 cm is thought to be the most useful cut-off value for distinguishing between less and more advanced PTC; this is reflected in the maintenance of a 2 cm cut-off between pT1 and pT2 tumours during pT staging using the recent tumour-node-metastases (TNM) classification [23]. However, according to the ATA or ESMO guidelines, low risk PTC larger than 1 cm but no larger than 4 cm are recommended for TL, as the outcome is not worse than that of TT [5, 21]. Nevertheless, the above studies show that higher risk features are more common in those with PTC 2–4 cm; our results are consistent with these findings. This leads to an interesting question: is a cut-off value of 2.0 cm really associated with a lower/higher risk of having one or more risk factor in those with PTC > 1–4 cm. The answer to this question could be essential when making the decision between the two surgical approaches, and should facilitate the choice between more appropriate treatment based on the risk of having aggressive disease that will require a second surgery after TL.

As expected, the cut-off value of 2 cm for pre-operatively low risk PTC is most likely the optimal value for identifying PTC patients in the > 1–4 cm group as having post-operatively ‘lower’ or ‘higher’ risk. Our data suggest that patients with PTC ≥ 2 cm in diameter had almost double the cumulative risk of having one or more aggressive risk factors such as vascular invasion, ETE, involved margin status, LN-positivity and DM compared with those with a smaller tumour of < 2.0 cm. The highest optimal cut-off value of 2.1 cm was established for the risk of DM. Our data may (in part) explain why patients with tumours > 2 cm showed higher mortality after TL in the recent meta-analysis by Zhang et al. [24]. On the other hand, Choi et al. reported that TL is sufficient and does not affect the long-term or oncological outcome of patients with low risk PTC of 1–4 cm, a finding supported by the recent study by Bosset et al. [25, 26].

This study has some limitations. First, although it used consecutive data from a single-centre, it was retrospective in nature, and analysis of medical records was limited only to available data from the past. Second, although prophylactic CND was performed in all studied patients, nearly 17% had an undetermined pathological LN-status (pNx), and the size of LN metastases was not reported in most final pathology reports covering LN-positive specimens. Thus, we included overall LN-positivity as a risk factor without excluding LN micro-metastases. Third, the relatively small number of patients with an aggressive subtype on final pathology potentially underpowers their importance in our analyses of the relationship between tumour size and the risk of having an aggressive histology. Finally, we examined the risk characteristics of those with PTC > 1–4 cm, as well as the relationship between tumour size and the risk of having a single, or the cumulative risk of having one or more risk factors, with the aim of establishing an optimal cut-off value for the tumour diameter associated with either of these. We did not assess the impact on long-term outcome, including overall survival or disease recurrence. The present study was intended to provide information that will be clinically useful and enable clinicians to make a risk–benefit analysis regarding selection of patients with PTC of 2 cm or less in > 1–4 cm tumours who are eligible for less intensive surgical management at the time of diagnosis with a current trend toward de-escalation of treatment.