Quality of Life in Patients with Papillary Thyroid Microcarcinoma Managed by Active Surveillance or Lobectomy: A Cross-Sectional Study

Abstract

Background:

Active surveillance (AS) is recommended as an alternative to immediate surgery in patients with papillary thyroid microcarcinoma (PTMC), but the impact of AS on quality of life has not been reported. The aim of this study was to compare quality-of-life parameters in patients with PTMC under AS versus those who underwent lobectomy (LB).

Methods:

In this cross-sectional study, patients with PTMC were prospectively enrolled between June 2016 and October 2017. All patients completed three questionnaires: the 12-item short-form health survey, thyroid cancer-specific quality of life, and fear of progression. The results were compared after adjusting for age, sex, and serum thyrotropin levels.

Results:

The AS group comprised 43 patients, and the LB group comprised 148 patients. According to the 12-item short-form health survey questionnaire, the score for role limitations due to emotional problems showed a significant negative association between the groups (coefficient [coef]: −7.71 [confidence interval (CI) −15.26 to −0.16], p = 0.045). The thyroid cancer-specific quality of life questionnaire also showed statistically significant differences between the groups with respect to three scores: neuromuscular problems (coef: 4.99 [CI 0.63–10.62], p = 0.020), throat/mouth problems (coef: 5.28 [CI 0.18–10.38], p = 0.043), and scar problems (coef: 9.34 [CI 4.38–14.29], p < 0.001), suggesting a higher level of complaint in the LB group than in the AS group. No significant differences in fear of progression scores were seen between the two groups.

Conclusions:

Patients with PTMC underwent LB experienced more health-related problems than those managed by AS. These findings support the role of AS as a reasonable management option for patients with PTMC.

Introduction

The global incidence of thyroid cancer has been increasing, with approximately 50% of this rise attributed to the greater detection of small papillary thyroid cancers (PTCs), particularly papillary thyroid microcarcinomas (PTMCs), which are PTCs with a maximum diameter of ≤1 cm (1 –3). As the risk of mortality or recurrence associated with PTMCs is low (1,4), recent studies have proposed management by active surveillance (AS) as an alternative to immediate surgery in patients with low-risk PTMCs (i.e., those without clinical lymph node metastasis or distant metastasis, clinical evidence of extrathyroidal extension of tumor, or vocal cord palsy) (5 –8).

AS is a management strategy for indolent malignancies, in which active treatment can be delayed until the cancer shows significant progression (5,9,10). Since first being introduced in patients with PTMCs (5,6), many studies have evaluated the oncologic outcomes in comparison with immediate surgical treatment. These studies showed no fatal recurrence or disease-specific mortality in patients under AS, suggesting that this approach is a safe management strategy (6,8,11,12). Therefore, recent guidelines developed by the American Thyroid Association include AS as an option for the management of patients with low-risk PTMC (2).

Although oncologic outcomes are the key consideration when assessing the efficacy of a new management approach, it is also important to consider any impact on health-related quality of life (HRQoL). Quality of life (QoL) assessment can demonstrate subjective symptoms associated with the disease itself or the side effects of treatment, as well as the real clinical benefits of the treatment for patients (13). However, evaluation of QoL according to their treatment modality has not been conducted in patients with PTMC to date.

This prospective study compared HRQoL of PTMC patients under AS versus those underwent lobectomy (LB) using three key questionnaires.

Methods

Subjects

Adult patients with cytopathologically diagnosed PTMC managed by AS or LB were prospectively enrolled from June 2016 to October 2017. Patients with evidence of disease progression or recurrent/persistent disease during follow-up (2), uncontrolled chronic disease or other malignancies, or a history of other malignancies were excluded. For patients under AS, PTMC was defined as a tumor with a maximum diameter ≤1 cm by ultrasound exam and with category 5 or 6 cytology according to the Bethesda system. Patients with evidence of lateral cervical lymph node or distant metastasis, macroscopic invasion, or invasion into the trachea or recurrent laryngeal nerve were excluded from AS at the authors' institution (8). During regular clinic visits, the study design was fully explained to the patients, and written consent was obtained. Patients then completed the three HRQoL questionnaires described below.

The study protocol was approved by the Institutional Review Board and was registered at the Clinical Research Information Service of the Korea Centers for Disease Control and Prevention (KCT0001986).

Demographic and clinical characteristics

Demographic characteristics, such as age, sex, marital status, education level, employment status, and socioeconomic status, were collected. Clinical characteristics, such as serum thyrotropin (TSH) level at the time of questionnaire completion, and data regarding levothyroxine (LT4) supplementation, were collected. The medical records of the patients were also reviewed to confirm the inclusion criteria.

HRQoL questionnaires

Short-form survey

The 12-item short-form health survey (SF-12; v2.0) is an abridged version of the SF-36 QoL questionnaire, comprising 12 questions covering eight domains: physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). The resultant score was transformed, and ranged between 0 and 100. The answers were combined and weighted to create the Mental Component Summary (MCS) score and Physical Component Summary (PCS) score using the QualityMetric Health Outcomes™ Scoring Software v5.0 (range 0–100). Higher scores indicate a better health status (14,15).

Thyroid cancer-specific quality of life questionnaire

The thyroid cancer-specific quality of life questionnaire (THYCA-QOL) is a 24-item questionnaire that assesses thyroid cancer-specific symptoms resulting from the thyroid cancer itself or its treatment. The THYCA-QOL includes seven multi-item scales: neuromuscular (problems such as cramping, and pain on joints or muscles), voice (the presence of hoarseness or weak on voice), concentration (attention problems or difficulty in thinking), sympathetic (the presence of hot flushes or heat intolerance), throat/mouth (problems when swallowing, feeling of a lump in the throat or dry mouth), psychological (anxiety, palpitations, or abrupt tiredness), and sensory symptoms (eye or skin problems such as dryness and itching), as well as six single scales (problems with scar, feeling chilly, tingling sensation, weight gain, headaches, and reduced interest in sex). All items were scored from 1 to 4 as follows: 1 = ”not at all,” 2 = ”a little,” 3 = ”quite a bit,” and 4 = ”very much.” A higher score indicates more complaints caused by that symptom (16,17).

Fear of progression questionnaire

The fear of progression (FoP) is 43-item questionnaire that assesses anxiety and fear related to disease progression. The items are divided into five subcategories: affective reactions (13 items), partnership/family (seven items), work (seven items), loss of autonomy (seven items), and coping with anxiety (nine items). Each is scored from 0 to 4: in most, a higher score indicates a greater level of anxiety about disease progression, with the exception of the final subcategory (coping with anxiety), in which higher score indicates a better level of coping (18 –20).

Statistical analyses

The data were analyzed using R studio (v3.1.3) and the R libraries readxl, lubridate, survival, car, and gdata (R Foundation for Statistical Computing, Vienna, Austria). Continuous variables are presented as the mean and standard deviation, or as the median and interquartile range. The t-test or Wilcoxon's test was used to compare continuous variables. Because only the log-transformed serum TSH values show normal distribution, serum TSH values were log-transformed and the geometric mean value was analyzed. Categorical variables are presented as numbers with percentages and were compared using the chi-square test. Univariate and multivariate regression analyses were used to compare the differences in scores between groups. All p-values were two-sided, and a p-value of <0.05 was considered statistically significant.

Results

Baseline patient characteristics

A total of 43 PTMC patients under AS and 148 PTMC patients who underwent LB, including 10 (7%) patients who underwent robotic surgery, were enrolled in the study. In comparison to the AS group, patients in the LB group were more likely to be female, have received LT4 treatment, and exhibit lower serum TSH levels. The time interval from initial diagnosis to questionnaire completion was also significantly different (29.6 months vs. 38.0 months, p < 0.001; Table 1). Among the 148 patients who underwent surgery, two had experienced transient postoperative hypoparathyroidism, one of whom required medication at the time of questionnaire completion.

Table 1.

Baseline Characteristics of Papillary Thyroid Microcarcinoma Patients

	Active surveillance (n = 43)	Lobectomy (n = 148)	p-Value
Age (years)	50.30 ± 10.57	51.00 ± 10.38	0.70
Sex (female)	29 (67)	126 (85)	0.017
Marital status
Married	38 (88)	124 (84)	0.62
Education level
College degree or higher	28 (65)	75 (51)	0.13
Current employment status
Employed	27 (63)	73 (49)	0.17
Socioeconomic status
Upper	16 (37)	64 (43)	0.70
Middle	22 (51)	65 (44)
Lower	5 (12)	19 (13)
Time interval from initial diagnosis (months)	29.6 (14.2–37.5)	38.0 (25.4–53.0)	<0.001
Serum TSH (mIU/L)^a	1.58 ± 2.55	1.00 ± 4.05	0.015
LT4 supplementation (yes)	5 (12)	130 (88)	<0.001

Continuous variables, except age and serum TSH, are presented as the median and interquartile range and assessed by Wilcoxon test.

Age and serum TSH levels are presented as the mean and standard deviation, and assessed by the T-test.

Categorical variables are presented as numbers with percentages and assessed by Chi-square test.

Geometric mean values were evaluated.

LT4, levothyroxine; TSH, thyrotropin.

Additional analysis was conducted to identify factors associated with the QoL of PTMC patients. Age as a continuous variable, sex, and serum TSH value as a continuous variable were significantly associated with many QoL parameters; time interval from initial diagnosis to questionnaire completion was not associated with any QoL parameters (Table 2). Therefore, for the multivariate analysis, data were adjusted for age, sex, and serum TSH value.

Table 2.

Factors Associated with the Quality of Life of Papillary Thyroid Microcarcinoma Patients

	Univariate analysis: age			Univariate analysis: sex			Univariate analysis: TSH			Univariate analysis: time interval
	Coef	CI	p-Value	Coef	CI	p-Value	Coef	CI	p-Value	Coef	CI	p-Value
SF-12v2
PCS	–0.12	[−0.21 to −0.02]	0.013	–2.22	[−4.69 to 0.25]	0.08	0.01	[−0.68 to 0.70]	0.99	0.009	[−0.04 to 0.06]	0.71
Physical functioning (PF)	–0.56	[−0.91 to 0.21]	0.019	–6.89	[−16.31 to 2.52]	0.15	–0.54	[−3.15 to −2.08]	0.69	0.05	[−0.13 to 0.23]	0.59
Role physical (RP)	–0.27	[−0.56 to 0.093]	0.08	–7.80	[−15.6 to 0.03]	0.051	–1.21	[−3.39 to 0.97]	0.28	–0.03	[−0.18 to 0.12]	0.67
Bodily pain (BP)	–0.23	[−0.51 to 0.04]	0.09	–9.51	[−16.66 to −2.36]	0.009	–0.53	[−2.52 to 1.48]	0.61	–0.004	[−0.14 to 0.13]	0.96
General health (GH)	–0.08	[−0.36 to 0.19]	0.55	–2.78	[−10.11 to 4.57]	0.46	0.42	[−1.61 to 2.45]	0.69	0.09	[−0.05 to 0.22]	0.22
MCS	–0.05	[−0.16 to 0.06]	0.41	–3.17	[−6.04 to −0.30]	0.031	–0.57	[−1.37 to 0.23]	0.16	0.02	[−0.03 to 0.08]	0.39
Vitality (VT)	–0.44	[−0.79 to −0.09]	0.013	–11.81	[−21.07 to −2.54]	0.013	0.65	[−1.95 to 3.25]	0.62	0.10	[−0.08 to 0.28]	0.27
Social functioning (SF)	–0.02	[−0.31 to 0.27]	0.88	–8.44	[−16.01 to −0.87]	0.03	–2.25	[−4.34 to −0.15]	0.036	0.12	[−0.03 to 0.26]	0.12
Role emotional (RE)	–0.003	[−0.30 to 0.30]	0.99	–4.73	[−12.70 to 3.24]	0.24	–2.13	[−4.32 to 0.056]	0.056	0.02	[−0.13 to 0.17]	0.81
Mental health (MH)	–0.28	[−0.54 to −0.03]	0.030	–7.13	[−13.87 to −0.39]	0.038	–0.62	[−2.50 to 1.27]	0.52	0.01	[−0.12 to 0.14]	0.86
THYCA-QoL
Neuromuscular	0.07	[−0.16 to 0.30]	0.53	9.56	[3.60–15.52]	0.002	2.26	[0.60–3.92]	0.008	–0.02	[−0.13 to 0.10]	0.76
Voice	0.23	[0.03–0.42]	0.025	2.72	[−2.54 to 7.99]	0.31	1.37	[−0.07 to 2.82]	0.06	0.04	[−0.06 to 0.14]	0.41
Concentration	0.19	[−0.04 to 0.42]	0.10	3.45	[−2.60 to 9.50]	0.26	1.83	[0.17–3.48]	0.031	0.06	[−0.06 to 0.17]	0.32
Sympathetic	0.06	[−0.19 to 0.31]	0.64	5.65	[−1.00 to 12.30]	0.01	1.35	[−0.49 to 3.19]	0.15	0.02	[−0.10 to 0.15]	0.73
Throat/mouth	0.20	[−0.01 to 0.40]	0.057	6.87	[1.48–12.25]	0.013	0.97	[−0.53 to 2.48]	0.21	–0.02	[−0.13 to 0.08]	0.65
Psychological	0.05	[−0.17 to 0.28]	0.65	6.59	[0.69–12.49]	0.029	2.34	[0.72–3.96]	0.01	–0.05	[−0.16 to 0.07]	0.41
Sensory	–0.03	[−0.28 to 0.22]	0.82	6.03	[−0.48 to 12.55]	0.07	0.84	[−0.97 to 2.65]	0.36	–0.06	[−0.18 to 0.07]	0.37
Problems with scar	–0.07	[−0.27 to 0.14]	0.53	4.43	[−0.95 to 9.82]	0.11	1.61	[0.13–3.09]	0.033	0.01	[−0.10 to 0.11]	0.91
Felt chilly	–0.13	[−0.36 to 0.10]	0.27	6.98	[0.99–12.96]	0.023	2.18	[0.53–3.83]	0.009	–0.03	[−0.14 to 0.09]	0.66
Tingling hands/feet	0.18	[−0.12 to 0.48]	0.24	8.24	[0.36–16.11]	0.041	1.42	[−0.77 to 3.61]	0.20	–0.08	[−0.23 to 0.07]	0.31
Gained weight	–0.23	[−0.53 to 0.07]	0.14	3.66	[−4.41 to 11.72]	0.37	1.51	[−0.72 to 3.72]	0.18	0.05	[−0.10 to 0.20]	0.52
Headache	–0.19	[−0.44 to 0.06]	0.14	6.43	[−0.28 to 13.15]	0.06	0.98	[−0.89 to 2.85]	0.30	–0.08	[−0.20 to 0.05]	0.24
Less interest in sex	–0.48	[−0.73 to −0.23]	<0.001	–20.26	[−26.54 to −13.97]	<0.001	–0.25	[−2.16 to 1.67]	0.80	–0.02	[−0.15 to 0.11]	0.75
Fear of progression
Affective reactions	–0.01	[−0.02 to 0.001]	0.08	0.25	[−0.04 to 0.54]	0.10	0.07	[−0.01 to 0.15]	0.07	–0.002	[−0.01 to 0.004]	0.53
Partnership/family	–0.01	[−0.02 to 0.001]	0.07	–0.08	[−0.32 to 0.16]	0.52	0.02	[−0.05 to 0.09]	0.54	0.001	[−0.004 to 0.006]	0.68
Work	–0.01	[−0.03 to −0.004]	0.008	0.01	[−0.28 to 0.30]	0.94	0.03	[−0.05 to 0.11]	0.46	0.00	[−0.008 to 0.003]	0.45
Loss of autonomy	–0.01	[−0.01 to 0.003]	0.19	0.04	[−0.20 to 0.27]	0.76	0.08	[0.01–0.14]	0.018	–0.002	[−0.006 to 0.003]	0.41
Coping with anxiety	–0.04	[−0.05 to −0.03]	<0.001	–0.05	[−0.41 to 0.30]	0.78	0.04	[−0.06 to 0.14]	0.39	–0.004	[−0.011 to 0.002]	0.20

Coef, coefficient; CI, confidence interval; SF-12v2, 12-item short-form health survey version 2.0; THYCA-QoL, thyroid cancer-specific quality of life questionnaire; PCS, Physical Component Summary; MCS, Mental Component Summary.

SF-12 questionnaire scores

The RP, SF, and RE scores were significantly lower in the LB group than in the AS group. In both the univariate and multivariate analyses, the RE score showed a significant negative linear association between groups (Coefficient [coef] −7.71 [confidence interval (CI) −15.26 to −0.16], p = 0.045 according to the multivariate analysis). These findings suggest a poorer health status in the LB group than the AS group (Table 3).

Table 3.

Comparison of Quality of Life in Patients with Papillary Thyroid Microcarcinoma Under Active Surveillance versus Those who Underwent Lobectomy

	Active surveillance	Lobectomy	p-Value ^*	Univariate analysis			Multivariate analysis
	Active surveillance	Lobectomy	p-Value ^*	Coef	CI	p-Value	Coef	CI	p-Value
SF-12v2
PCS	52.75 ± 5.66	51.06 ± 7.09	0.11	–1.67	[−4.01 to 0.64]	0.15	–1.31	[−3.66 to 1.04]	0.27
Physical functioning (PF)	52.30 ± 6.22	50.25 ± 8.59	0.09	–6.53	[−14.35 to 2.29]	0.15	–5.59	[−14.45 to 3.27]	0.21
Role physical (RP)	49.79 ± 6.74	47.37 ± 7.41	0.047	–7.14	[−14.48 to 0.20]	0.056	–6.38	[−13.83 to 1.08]	0.09
Bodily pain (BP)	53.32 ± 6.64	41.28 ± 7.33	0.34	–3.16	[−9.96 to 3.64]	0.36	–1.63	[−8.50 to 5.24]	0.64
General health (GH)	50.62 ± 6.84	48.97 ± 8.27	0.19	–3.07	[−10.99 to 2.72]	0.24	–3.63	[−10.70 to 3.44]	0.31
MCS	48.75 ± 8.18	47.02 ± 7.86	0.22	–1.73	[−4.44 to 0.98]	0.21	–1.41	[−4.16 to 1.35]	0.32
Vitality (VT)	50.67 ± 10.93	49.73 ± 9.91	0.62	–2.38	[−11.19 to 6.43]	0.60	0.13	[−8.70 to 8.96]	0.98
Social functioning (SF)	53.18 ± 5.57	51.01 ± 7.87	0.045	–6.09	[−13.22 to 1.04]	0.09	–5.61	[−12.80 to 1.60]	0.13
Role emotional (RE)	48.42 ± 7.81	45.32 ± 9.34	0.031	–7.46	[−14.87 to −0.44]	0.049	–7.71	[−15.26 to −0.16]	0.045
Mental health (MH)	48.47 ± 9.62	47.46 ± 8.24	0.54	–2.18	[−8.56 to 4.19]	0.50	–1.08	[−7.53 to 5.37]	0.74
THYCA-QoL
Neuromuscular	43.60 ± 14.07	49.32 ± 17.24	0.029	5.72	[0.52 to 11.39]	0.048	4.99	[0.63 to 10.62]	0.020
Voice	34.30 ± 12.82	37.25 ± 14.83	0.21	2.94	[−1.98 to 7.87]	0.24	3.02	[−1.95 to 7.99]	0.23
Concentration	37.79 ± 13.22	42.82 ± 17.32	0.045	5.03	[−0.61 to 10.67]	0.08	5.25	[−0.45 to 10.95]	0.07
Sympathetic	42.73 ± 17.09	47.72 ± 18.56	0.10	4.99	[−1.25 to 11.22]	0.12	4.64	[−1.73 to 11.00]	0.15
Throat/mouth	34.50 ± 11.58	40.48 ± 15.48	0.007	5.99	[0.43 to 11.04]	0.021	5.28	[0.18 to 10.38]	0.043
Psychological	43.46 ± 15.84	46.03 ± 16.48	0.36	2.57	[−3.01 to 8.16]	0.37	2.29	[−3.29 to 7.88]	0.42
Sensory	47.38 ± 13.79	48.56 ± 19.04	0.65	1.18	[−4.97 to 7.33]	0.71	0.40	[−5.88 to 6.69]	0.91
Problems with scar	25 ± 0	34.12 ± 16.27	<0.001	9.12	[4.22 to 14.03]	<0.001	9.34	[4.38 to 14.29]	<0.001
Felt chilly	33.14 ± 11.85	38.01 ± 17.61	0.038	4.87	[−0.77 to 10.51]	0.09	4.61	[−1.01 to 10.23]	0.11
Tingling hands/feet	46.51 ± 19.35	50.68 ± 22.39	0.23	4.16	[−3.27 to 11.60]	0.27	3.27	[−4.29 to 10.83]	0.39
Gained weight	40.70 ± 16.39	45.78 ± 23.40	0.11	5.08	[−2.45 to 12.61]	0.19	5.25	[−2.42 to 12.91]	0.18
Headache	41.86 ± 14.14	44.76 ± 19.62	0.28	5.24	[−3.43 to 9.24]	0.37	2.22	[−4.20 to 8.64]	0.49
Less interest in sex	51.16 ± 21.79	41.89 ± 17.55	0.013	–9.27	[−14.62 to −2.92]	0.004	–5.81	[−11.65 to 0.04]	0.052
Fear of progression
Affective reactions	2.07 ± 0.89	2.03 ± 0.78	0.77	–0.04	[−0.32 to 0.23]	0.75	–0.06	[−0.34 to 0.21]	0.65
Partnership/family	1.84 ± 0.65	1.87 ± 0.67	0.85	0.02	[−0.21 to 0.25]	0.85	0.05	[−0.18 to 0.28]	0.68
Work	1.56 ± 0.78	1.64 ± 0.81	0.56	0.08	[−0.19 to 0.35]	0.56	0.10	[−0.18 to 0.37]	0.49
Loss of autonomy	1.79 ± 0.74	1.65 ± 0.62	0.28	–0.14	[−0.36 to 0.09]	0.23	–0.12	[−0.34 to 0.10]	0.29
Coping with anxiety	3.06 ± 0.98	2.95 ± 0.97	0.49	0.17	[−0.45 to 0.22]	0.49	–0.09	[−0.40 to 0.22]	0.58

The scores are presented as the mean and standard deviation.

In multivariate analysis, age, sex, and serum TSH levels were adjusted.

p-values were assessed by the T-test.

THYCA-QOL questionnaire scores

Scores relating to the “neuromuscular,” “concentration,” “throat/mouth,” “problems with scar,” and “feeling chilly” scales were significantly higher in the LB group than in the AS group, suggesting a higher level of complaints relating to these symptoms in the LB group. The “less interest in sex” scale showed a significantly higher score in the AS group than in the LB group (Table 3).

In the univariate and multivariate analyses, the “neuromuscular,” “throat/mouth,” and “problems with scar” scale scores also showed a significant positive association between the groups: neuromuscular problems (coef: 4.99 [CI 0.63–10.62], p = 0.020), throat/mouth problems (coef: 5.28 [CI 0.18–10.38], p = 0.043), and scar problems (coef: 9.34 [CI 4.38–14.29], p < 0.001). The “less interest in sex” scale score showed a significant difference between the groups in the univariate analysis but not in the multivariate analysis (Table 3).

FoP questionnaire scores

No significant differences were seen in FoP scores between the two groups in all analyses (Tables 3).

Discussion

This study evaluated HRQoL among patients with PTMC according to their mode of treatment. Some significant differences were seen in parameters of the SF-12 and THYCA-QoL questionnaires between the LB and the AS groups. After adjusting for age, sex, and serum TSH levels, the LB group reported more problems relating to RE than the AS group, and the RE scores showed significant negative association between groups. Furthermore, neuromuscular, throat/mouth, and scar problems were more prevalent in the LB group than in the AS group. These problems are likely to have resulted from surgery. The study also analyzed differences in the parameters between open and robotic surgery, but QoL parameters did not differ significantly between the two groups, with the exception of scar problems (p = 0.002, data not shown). These results suggest that patients with PTMC who have undergone LB had more health-related problems than those under AS, which may be related to surgery, despite the fact that patients were in a stable state more than three years post surgery and also had sufficient thyroid hormones.

Analysis of the anxiety and fear related to disease progression using the FoP questionnaire (18,21) showed no significant differences between the two groups. However, patients in the AS group reported less interest in sexual activity, with marginal statistical significance after adjustment, which may be associated with some anxiety resulting from their untreated cancer. A previous study has suggested that loss of sexual desire is the most common sexual problem in patients with cancer (22).

The three different questionnaires used in this study have previously been validated for the assessment of HRQoL. Among them, the THYCA-QoL questionnaire was the most sensitive in detecting differences in HRQoL in the current study. In a previous study, thyroid cancer-specific symptoms, such as neuromuscular, sympathetic, concentration, and psychological problems, were seen to be strong determinants of the HRQoL of thyroid cancer survivors (23). These results are consistent with the current study, and suggest that the THYCA-QoL questionnaire is the most appropriate tool for assessing thyroid-specific symptoms and HRQoL in thyroid cancer survivors.

Since the concept of AS was first introduced in patients with PTMCs, many studies have demonstrated that this approach may provide safe and effective management of low-risk PTMCs, particularly in older patients (2,5,6,9). The current study suggests that AS may also have advantages in terms of patient HRQoL and supports the role of AS in patients with PTMC. The data also suggest that surgical treatment is associated with poorer HRQoL and that leaving PTMCs untreated under AS is not associated with increased anxiety or fear related to disease progression.

This study has some limitations, primarily that the baseline characteristics of patients in each treatment group were significantly different. Although the multivariate analysis was adjusted for patient age and sex, which are key factors in the assessment of HRQoL (14), as well as serum TSH levels, the results of this study can be biased. In addition, as patients who had uncontrolled chronic disease or other cancers were excluded, the number of patients included in this study, particularly in the AS group, was limited. However, this study highlights significant differences in the HRQoL between patients with PTMC under AS and those who have undergone LB, particularly with respect to thyroid cancer-specific symptoms. Further evaluation of HRQoL in patient with PTMC who underwent immediate surgery versus those who underwent delayed surgery after AS is required. This is a cross-sectional study, and further analysis in a prospective study including the collection of patient-reported outcomes, repeated assessment, and longer follow-up is required to confirm the findings.

In conclusion, patients with PTMC experienced more health-related problems after undergoing LB than those under AS did. These findings suggested that AS offers advantages in terms of HRQoL and supports the role of AS as a valid management option for patients with PTMC.

Footnotes

Acknowledgments

This study was supported by a grant of the Korean Health Technology R&D project, Ministry of Health & Welfare, Republic of Korea (HC15C3372). The Journal acknowledges that author retains the right to provide an electronic copy of the final peer-reviewed manuscript to Korea PubMed Central (PMC) upon acceptance for publication, and make it publicly available as soon as possible but no later than 12 months after publication.

Author Disclosure Statement

The authors have nothing to disclose.

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