*Yasuhiro Ito
Department Of General Surgery, Kuma Hospital, Japan
Published on: 2014-01-20
Papillary thyroid carcinoma (PTC) is generally indolent, but it may display a poor prognosis if it has aggressive clinicopathological features
Papillary thyroid carcinoma (PTC) is generally indolent, but it may display a poor prognosis if it has aggressive clinicopathological features. In the past, especially in Western countries, treatment for PTC has been standardized: total or near total thyroidectomy with or without lymph node dissection followed by radioactive iodine (RAI) ablation and thyroid-stimulating hormone (TSH) suppression. In Japan, in contrast, the incidence of total thyroidectomy has traditionally been low, and due to the legal restrictions concerning RAI use, RAI ablation has not been common.
Papillary microcarcinomas (PMCs) are PTC≤1cm. In 1993, Akira Miyauchi at Kuma Hospital, Japan proposed observation without immediate surgery for cases of low-risk PMC lacking distant metastases (M), clinical node metastases (N) and symptoms (such as recurrent laryngeal nerve paralysis) due to significant carcinoma extension (Ex). The observation trial trial started the same year. To date, two institutions in Japan have continued to conduct this trial, and they have published promising results [1-4]. Based on these studies’ data, the therapeutic strategy proposed by Miyauchi was adopted for use in the treatment guidelines issued by the Japanese Society of Thyroid Surgeons and the Japan Association of Endocrine Surgeons, published in 2010 [5] and this strategy is now beginning to spread to other countries such as the United States.
The most recent study, which enrolled 1,235 patients with 1.5-19 years’ observation, found that the 10-year size enlargement and novel node appearance rates were 8.0% and 3.8%, respectively, and interestingly, the study revealed that PMC are less likely to progress in old patients than in young and middle-aged patients [4]. Importantly, it is not too late to surgically treat patients after the detection of progression signs of their PMC such as size enlargement and the novel appearance of lymph node metastasis.
There are merits and demerits of total and limited thyroidectomy. The incidences of hypoparathyroidism and bilateral recurrent laryngeal nerve paralysis are much lower in patients who undergo a limited thyroidectomy. In addition, the administration of L-thyroxine may not be needed in patients who have undergone a limited thyroidectomy. Severe complications such as recurrent laryngeal nerve paralysis and persistent hypoparathyroidism may occur in total thyroidectomy, depending on the surgeon’s skill. Thyroglobulin (Tg) and Tg-antibody (TgAb) can be used as markers of recurrence or carcinoma remnant after total thyroidectomy, which makes various imaging studies such as CT scans and roentogenography unnecessary for postoperative follow-up [6]. When a patient’s Tg and/or TgAb levels are elevated, immediate RAI ablation/ therapy can be performed. After a total thyroidectomy, TSH suppression is generally performed, but it was demonstrated that mild TSH suppression does not imply hyperthyroidism. Matsuzu et al. showed that the 25-year lymph node and distant recurrence-free survival rates of 381 patients with PTC≤4 cm with N (−), M (−), or Ex (−) were 92.5% and 99.6%, respectively, even though all of the patients underwent a hemithyroidectomy rather than a total or near total thyroidectomy in Japan [7]. Our institutionpublished similar results, although at present published similar results, although at present, we normally perform a total thyroidectomy for low-risk PTC>2 cm, because its prognosis is poorer than that of low-risk PTC (≤2cm) [8]. At the least, we can conclude that routine total thyroidectomy is not needed for low-risk PTC patients. Total thyroidectomy is strongly or moderately recommended in our guidelines for PTC with N (+), Ex (+) or large size, because of the increased risk of distant recurrence requiring RAI therapy [5]. This guideline can be expected to increase the use of total thyroidectomy for PTC patients in Japan.
In 2010, we investigated the prognosis of 2,638 T1N0M0 PTC patients [9]. Although only three of the patients underwent RAI ablation, the 10-year disease-free survival (DFS) rate of T1N0M0 patients was excellent, at 97%. A more recent study of a large number of patients, although not randomized, showed that the overall survival (OS) and DFS rates for lowrisk (pT1 or T2, N0 or NX) PTC based on American Thyroid Association (ATA) guidelines [10] were not related to whether the patients underwent RAI ablation [11].
In addition, RAI may result in adverse events such as sialadenitis, dental caries, marrow suppression, gonadal dysfunction, and second malignancy [12]. The ATA guidelines will be revised in 2014, and they will describe that RAI ablation/adjuvant therapy is mandatory only for PTC with high-risk features (M1/any N/any M or T4/any N/any M). In Japan, RAI ablation using 30 mCi of RAI in outpatient clinics was recently allowed, and our guidelines also recommend RAI ablation for high-risk PTC cases such as those with Ex (+), a large number of N, and aggressive pathological histology such as a tall-cell variant, as well as the presence of persistent disease or distant metastasis [5]. Our guidelines are also to be revised in the near future, including this aspect and the indications for RAI ablation in Japan and Western countries are thus gradually becoming similar.
Another question is whether RAI ablation is truly mandatory for all high-risk PTC patients immediately after total thyroidectomy. Not all persistent diseases are progressive, and Tg levels are stable and not elevated (or even decreased during follow-up) in these patients. We have observed that the Tg levels often became lower than the measurement sensitivity, even in high-risk cases after surgery. It is therefore debatable whether immediate RAI ablation is necessary for such patients. Miyauchi et al. showed that a short Tg-doubling time (< 2 years) predicts a poor prognosis [13] They also described that a large proportion of their patients with detectable serum Tg levels showed a decrease in these levels over time, and such patients had excellent prognoses [13] indicating that RAI ablation when a Tg elevation is detected may be adequate.
It is interesting that therapeutic strategies for PTC are coming closer, although very gradually, between Western countries and Japan. As indicated above, the ATA guidelines and ours are being revised in the near future, and the efforts to identify the best treatment for each patient with thyroid carcinoma (including PTC) should continue.
