Over the last decade, the incidence of differentiated thyroid cancers (DTCs), including papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma, has increased worldwide [1-3]. Of particular note, in Korea, the annual incidence of thyroid cancer rose from 6.3 cases per 100,000 in 1999 to 52.7 cases per 100,000 in 2010, which represents a 25% annual increase over the last 10 years [4]. According to the United States population-based data from the Surveillance, Epidemiology, and End Results program from 2006 to 2012, PTC was most frequently diagnosed in patients aged 45-54 years, and approximately 20% of cases of thyroid cancer occurred in patients older than 65 years [5]. In the 2015 Korean Central Cancer Registry, thyroid cancer was reported to be the fourth most common cancer in women aged 65 years or older [6]. Despite its slow progression and highly favorable prognosis, PTC tends to show more aggressive histologic features, a greater tumor size, extensive local growth, and more frequent distant metastasis in elderly patients than in younger patients, leading to a poor prognosis with increased risks of recurrence and thyroid cancer-related mortality [7-16]. Therefore, the surgical treatment of thyroid cancer, such as total thyroidectomy and subsequent lifelong thyroid hormone replacement therapy, has inevitably become more common in the elderly based on the poor outcomes associated with advanced age, although most cases of PTC that have been recently diagnosed after the widespread implementation of screening ultrasonography (US) have been reported to be papillary thyroid microcarcinoma (PTMC), measuring 1 cm or less [1,3,17,18]. Some studies have advocated total thyroidectomy for elderly patients with PTC [7,8,14,19,20]. However, concerns have been raised about the possibility of postoperative subclinical thyrotoxicosis induced by thyrotropin suppression therapy, which can have cardiovascular effects or cause significant bone loss, particularly in older women [21,22].

To our knowledge, few studies have been conducted to support treatment decision-making in elderly patients with PTC [7,8,11,15,19,21]. In order to obtain reliable data on the initial diagnosis and postsurgical outcome of recently diagnosed PTC, patients’ clinical features should be obtained from an institution where regular sonographic evaluations have been included in postoperative surveillance to detect small sized local recurrence. In addition, to understand the recently increased diagnosis of PTC, it would be helpful to review institutional records in Korea, where the incidence of PTC (age-standardized rate, 58.3% per 100,000 population) has been reported to be more than 15 times greater than that of the UK and 5.6 times that of the United States, according to GLOBOCAN 2012 [23]. Herein, we reviewed the characteristics of patients aged 65 years and older who underwent surgery for PTC at a single institution and were subsequently followed by ultrasonography during the past 10 years to facilitate the prediction of recurrence.

Unlike in other malignancies, the patient’s age has been regarded as an independent risk factor for PTC [10-14]. However, the reported data are insufficient to specifically address PTC recently diagnosed in elderly patients. Most staging systems have chosen the cutoff of 45 years of age to differentiate low-risk DTC from high-risk DTC [16,28,29]. Moreover, various cutoff ages, such as 60, 65, 75, or 85 years, have been used to evaluate the clinical features of elderly patients due to the lack of a precise definition of “old age” [7,8,10,11,13-15,19]. Therefore, the actual proportion of elderly patients who have been reported to undergo elective thyroid surgery ranges from 2.5% to 21.2%, depending on the criteria used for patient selection.

To the best of our knowledge, this is the first study to reflect the recently increased diagnosis of asymptomatic PTMC in elderly patients, although the overall survival was not fully evaluated because of the relatively short follow-up period. Based on initial and serial sonographic surveillance in the past 10 years, 83 patients (55.3%) were diagnosed with PTMC among the 150 patients aged 65 and older with PTC, and the overall rate of recurrence was 12.5% (17 of 139) among patients who were followed up for a mean of 43.3 months.

In this study, tumor size and LNM were identified as independent predictors of recurrence in elderly patients with PTC, which is consistent with previous studies that reported that size, local extent (T staging) and nodal status (N staging) were important prognostic factors in patients 45 years or older [16,20,28-30]. In addition, the HR of LNM was greater than that of tumor size (more than 9-, 14-, and 58-fold higher with LNM in the central, lateral, and both central and lateral compartments, respectively, than in those without any LNM, as compared to a twofold increase with each 1-cm increment in tumor size), indicating that LNM may be more closely associated with recurrence in the elderly than tumor size. Since US is widely recognized to be the preoperative imaging modality of choice to assess LNM in cases of PTC [24-26], the diagnostic role of preoperative US cannot be overemphasized for elderly patients with PTC.

PTMC has been considered to be an indolent disease due to its low risk of recurrence and high overall survival [31,32]. The recurrence rate of our elderly patients with PTMC was 2.7%, which is similar to the result of a recent 11-year observation of PTMC patients from 2000 to 2011, which revealed that only six of 202 patients (mean age, 49 years; range, 15 to 83 years) experienced recurrence after surgery, with a median time to recurrence of approximately 12 months [33]. These results are also compatible with those of a 10-year observational study of 1,235 patients with low-risk PTMC that was conducted by Ito et al. [31]. They emphasized the presence of significant age-specific differences in tumor biology between subclinical PTMC and clinically advanced PTC; for example, the incidence of larger tumors, LNM, and progression to clinical disease was lowest in oldest patients (≥60 years) and highest in the youngest patients (<40 years) [31]. At the time of their initial diagnosis, our elderly patients with PTMC likewise showed significantly fewer cases of ETE and LNM, which led to a lower postoperative recurrence rate than was observed among those with non-PTMC, even with a relatively short followup interval. Accordingly, elderly patients with subclinical PTMC have been recommended as candidates for observation rather than immediate surgery [31,34]. In another study, Ito et al. [35] concluded that thyroid surgery is not always necessary unless a patient exhibits LNM, multiplicity, a positive family history, or other pathological lesions in the contralateral lobe.

Our results differ from those of previous studies that recruited elderly patients with PTC in several aspects. First, a relatively high percentage (42.3%) of elderly patients underwent surgical resection for asymptomatic PTMCs. This is related to the unique medical environment in Korea. Since 2002, thyroid US has become an optional workup in health promotion programs at most hospitals in Korea, meaning that people can easily undergo US screenings at a cost of $30-$50, which has led to an abrupt increase in the detection and treatment of PTC [3,18]. For this reason, the frequency of thyroid cancer diagnoses has increased in Korea 15-fold over the past 20 years [6,18]; however, the mortality rate has remained almost constant during the past 3 decades [3,17,18]. Even in the elderly population, the majority of newly diagnosed cases of thyroid cancer in Koreans are small PTCs that infrequently exhibit LNM or ETE [3]. Second, the recurrence rate found in this study (12.5%) is less than one-third of the rate of 39% that was obtained in a study with a larger population of 2,883 patients over 65 years of age who were diagnosed with DTC between 1995 and 2007 [15]. This difference may be explicable in part based on the availability of detailed preoperative US examinations. Currently, prior to surgery, experienced radiologists carefully examine the primary thyroid tumor and the adjacent neck lymph nodes, like in our hospital; therefore, postoperative recurrence has markedly declined, irrespective of the patient’s age at initial presentation [24-26]. On the contrary, preoperative US was not routinely performed during the early period of that study (from 1995 to 2007). Therefore, the higher recurrence rates in the previous studies can be explained by the initially missed nonpalpable lymph nodes, which became clinically evident years after surgery. For similar reasons, age was not regarded as an independent predictor of recurrence in a recently published observational study of a Chinese cohort of 407 PTC patients, regardless of whether age was entered as a categorical or continuous variable, as in this study [13].

Due to the recent rapid increase in the life expectancy of the general population, the elderly population has increased by 90% over the last 30 years. Based on the 2010 United States Census, by 2030, more than 20% of United States residents are projected to be aged 65 and over, compared with 13% in 2010 and 9.8% in 1970, in addition, the population aged 65 and over is projected to be 83.7 million in 2050, almost double the corresponding figure of 43.1 million in 2012 [36]. Unlike the younger population, elderly patients often have concomitant medical problems, some of which may be potentially lethal conditions such as cardiovascular, respiratory, or renal disease. If they undergo total thyroidectomy for thyroid cancer, there is a small but significant risk of operative complications, such as vocal cord paralysis or hypoparathyroidism, and lifelong thyroid hormone replacement may be needed [21]. Based on our 10-year single-institution experience, we advocate a tailored approach to develop appropriate treatment or follow-up plans in elderly patients depending on the tumor size and the extent of ETE or LNM [2,21,34]. More aggressive treatment (total thyroidectomy and subsequent RAIT) or more frequent follow-up should be considered only for patients with a larger tumor, wide ETE, or lateral LNM, all of which can be predicted by preoperative radiologic assessment. In contrast, a more conservative management strategy, including active surveillance rather than immediate surgery, would be preferred for elderly patients with PTMC, which shows less frequent ETE or LNM, as in a recently published risk stratification [37].

Nonetheless, our study has several limitations. First, given the indolence of PTC, including PTMC, this study was conducted over a relatively short follow-up period (mean, 43.3 months; range, 6 to 100 months); therefore, it was not possible to fully assess the impact of the characteristics of PTC on late recurrence and late death. Second, to elucidate the prognostic factors of recently diagnosed PTC in elderly patients, we enrolled a small number of elderly patients with PTC treated at a single institution. A larger population-based prospective study should be performed in various regions and hospital settings with a longer follow-up period to support our results. Third, because of the retrospective design of this study, it was not possible to adjust for some confounding factors, such as the surgeon’s preference for thyroid surgery for elderly patients, so some patients diagnosed with PTMC underwent total thyroidectomy, especially during the earlier period.

In conclusion, PTCs of small size and absent LNM showed significantly better prognoses in patients 65 years and older. Therefore, a tailored treatment approach should be established for elderly patients with PTC, in which the treatment strategy can be primarily determined by the patients’ US findings.