Fear of Recurrence and View of Life Affect Health-Related Quality of Life in Patients with Differentiated Thyroid Carcinoma: A Prospective Swedish Population-Based Study

Abstract

Background:

Differentiated thyroid cancer (DTC) has a good prognosis but a remaining risk of recurrence and need for lifelong follow-up. The aim was to study changes in health-related quality of life (HRQoL) from diagnosis to one year of follow-up.

Methods:

In this prospective population-based study, patients were identified from all the Swedish departments of oncology treating DTC. In total, 487 patients diagnosed with DTC between 2012 and 2017 were invited to answer the Swedish version of the Short Form-36 Health Survey (SF-36) and a study-specific questionnaire at diagnosis and after one year.

Results:

In total, 349 (72%) patients responded. Of these, 235 (67%) had reached one year of follow-up and also answered the questionnaire after one year. Of those, 23% had a negative view of life, and 75% had a fear of recurrence at diagnosis. These patients had a significantly lower HRQoL on eight and five of the SF-36 domains, respectively (p < 0.05). A negative view of life and a fear of recurrence also affected HRQoL negatively after one year of follow-up, with a significantly lower HRQoL on seven SF-36 domains for those reporting a negative view of life or fear of recurrence often (p < 0.05). Thyrotropin suppression did not affect HRQoL negatively. In regression models, HRQoL at diagnosis was the most important predictive factor for HRQoL at the one-year follow-up.

Conclusions:

Despite a good prognosis, HRQoL was substantially affected at the time of diagnosis, with some improvements after one year. As fear of recurrence and a negative view of life substantially affect HRQoL, these patients should be given additional attention.

Introduction

Differentiated thyroid cancer (DTC) is the most common endocrine cancer, with an increasing incidence worldwide. In Sweden, the incidence was 7/100,000 in 2015 compared to 3.4/100,000 10 years earlier (1,2). Treatment consists of total thyroidectomy, lymph node dissection when appropriate, radioiodine (RAI) treatment, and levothyroxine in doses suppressing thyrotropin (TSH). Although the prognosis is good, with a 10-year survival >90% (3), the recurrence risk is >20%, and late recurrences can appear even decades after diagnosis (4). However, even distant metastases have a quite favorable prognosis, with a survival of several years (5,6).

Health-related quality of life (HRQoL) in thyroid cancer has been increasingly investigated over the last few years. Several studies have revealed a lower HRQoL compared to the general population (7 –9). More surprisingly, HRQoL in DTC patients is at the same level as in patients with more aggressive cancer diagnoses (10).

Fatigue, sleeping disorders, and irritability are common symptoms affecting HRQoL (8,11), and conditions such as anxiety and depressive mood are as frequent as in other cancer diagnoses (12). Although the prognosis is good, a fear of recurrence is frequent and constitutes one cause of lower HRQoL (9,13,14). TSH suppression has also been suggested as one reason for a decreased HRQoL. Restoration to normal TSH levels has, however, not increased HRQoL (15). Thus, the effect of TSH suppression and its effects on HRQoL during follow-up are not fully understood.

Although HRQoL in thyroid cancer patients has been more extensively investigated in cross-sectional studies, the course of HRQoL over time has not been fully studied. Therefore, a prospective, population-based study was conducted to investigate HRQoL in DTC patients.

The aims were to study changes in HRQoL over time and whether factors such as TSH levels, fear of recurrence, actual recurrence, and view of life affect HRQoL. Further, the study wanted to identify factors at diagnosis predictive of HRQoL at one year of follow-up.

Methods

Study design and population

A population-based, nationwide, prospective study was performed between January 2012 and March 2017 in Sweden. Patients were included from all Swedish departments of oncology/surgery treating thyroid cancer patients with radioactive iodine (RAI). Patients were followed for one year. Inclusion criteria were: age ≥18 years at diagnosis, Swedish-speaking, a primary diagnosis of DTC, scheduled for a total thyroidectomy with or without lymph node dissection, and RAI treatment. Exclusion criteria were: small DTC (T1a) not planned for RAI treatment, ongoing treatment for other malignancies, anaplastic or medullary thyroid cancer, or a recurrence of DTC. Patients were identified during the postoperative multidisciplinary conference and included after surgery but before RAI treatment. All 13 hospitals in Sweden administering RAI treatment participated in recruitment. Patients were invited to participate by mail, and by completing and returning questionnaires, they consented to their participation and their data being used for research purposes. Up to three letters were sent to non-responders as a reminder.

The study was approved by the Regional Ethical Review Board in Stockholm (2011/718-31/2).

Data collection and categorization

Sociodemographic variables and comorbidities

At diagnosis, participants were asked to report information regarding their age, sex, level of education, occupation/employment, and, for women, menopausal status. Patients also listed comorbidities diagnosed by a physician. The following comorbidities were asked for in a no/yes format: previous myocardial infarction, hypertension, atrial fibrillation, previous stroke, diabetes, chronic obstructive pulmonary disease, asthma, kidney failure, rheumatoid arthritis/osteoarthritis, osteoporosis, depression under treatment, other psychiatric disease, other cancer, or any other specified disease. Comorbidities were subsequently grouped into “none,” “one,” or “at least two.”

Cancer-related variables

Clinical characteristics (surgery, histology, tumor stage, RAI treatment, possible external radiation treatment or other medical treatments, TSH, and recurrences) were collected from patients' medical charts. Information was gathered at diagnosis and at the one-year follow-up. Additionally, patients reported recurrences and possible treatments in their questionnaires. TSH was divided into three groups according to American Thyroid Association guidelines (16): moderate or complete suppression was defined as TSH <0.1 mIU/L, mild suppression as TSH 0.1 to <0.4 mIU/L, and no suppression as ≥0.4 mIU/L.

HRQoL

HRQoL was assessed with the Swedish version of the Short Form-36 Health Survey (SF-36), v2.0 (17,18), a well-validated and standardized questionnaire measuring general health that is used in many publications (19). The SF-36 is a multipurpose, short-form survey with 36 questions measuring both physical and mental health. Responses were linearly transformed to a score between 0 and 100 according to the SF-36 scoring manual (20). A higher score on the domains signifies lower disability and better HRQoL. The SF-36 contains eight domains: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH).

View of life and fear of recurrence

Additionally, a study-specific questionnaire was developed as a complement to the SF-36. At the beginning of the study, no validated HRQoL questionnaires suitable for thyroid cancer patients were available in Swedish. The study-specific questionnaire included questions regarding a patient's view of life and fear of recurrence. To capture how an individual's view of life was affected by disease, patients were asked whether the disease had affected their view of life, and their answers were divided into “no,” “yes, in a positive way,” and “yes, in a negative way.” Fear of recurrence was divided into three groups: “never,” “seldom,” and “often.”

Predictive factors affecting HRQoL

To identify factors at diagnosis predictive of HRQoL measured with SF-36 at the one-year follow-up, the effect of the following factors was investigated: age, sex, education, marital status, comorbidities, view of life, fear of recurrence, T- and N-status, and the corresponding SF-36 domain at diagnosis (e.g., PF at diagnosis was used to predict PF at one year).

Statistical analysis

Patient characteristics were described by standard descriptive statistics (Table 1). Statistical differences were tested with a Mann–Whitney U-test, Kruskal–Wallis test, or Wilcoxon signed-rank test at the 0.05 level. As statistical significance alone is not sufficient when evaluating HRQoL data, minimally important difference (MID) was used as a complement. MID is defined as the smallest difference in scores that patients experience to be important (21). In a comparison of SF-36 on all domains (scale 0–100), differences of 5–10, 10–20, and >20 were interpreted as clinically relevant, minimally important, moderately important or considerable different, respectively (22).

Table 1.

Patients Characteristics, Treatments, and Recurrences of 235 Patients with DTC

	n (%)
Sex
Male	70 (30)
Female	165 (70)
Age (years)
18–39	74 (32)
40–49	47 (20)
50–59	34 (14)
60–69	45 (19)
70–79	21 (9)
80–88	14 (6)
Education
Low (elementary school ≤9 years)	36 (15)
Medium (secondary school 10–12 years)	82 (35)
High (university >12 years)	117 (50)
Comorbidity
None	111 (47)
Yes, one	71 (30)
Yes, at least two	53 (23)
Marital status
Married/partner	174 (74)
Living alone	61 (26)
Menopause
Yes or ongoing	68 (41)
No	97 (59)
Histology
Papillary	188 (80)
Follicular	47 (20)
Tumor stage^a
T0	2 (<1)
T1	77 (33)
T2	70 (30)
T3	82 (35)
T4	4 (2)
N0	36 (15)
N1a	74 (32)
N1b	38 (16)
Nx	87 (37)
M1	1 (<1)
Mx	234 (100)
Thyroid surgery
Total thyroidectomy	234 (100)
Hemi thyroidectomy	1 (<1)
Neck dissection
None	79 (34)
Central	118 (50)
Central + lateral	38 (16)
Radioactive iodine therapy
No radioiodine	4 (2)
1.1 GBq	38 (16)
3.7 GBq	174 (74)
5.4 GBq	15 (6)
7.4 GBq	4 (2)
External radiotherapy
None	230 (98)
Yes	5 (2)
Recurrent disease at one year
No recurrence	207 (88)
Abnormal Tg	5 (2)
Locoregional recurrence	13 (6)
Distant metastases	10 (4)

Tumor stage was assessed before radioiodine treatment.

DTC, differentiated thyroid cancer; HRQoL, health-related quality of life; Tg, thyroglobulin; GBq, giga Becquerel.

To identify factors at diagnosis predictive of HRQoL at the one-year follow-up, the responses to SF-36 were dichotomized into “good” and “poor.” Patients answering “no” or “little” symptoms/impact on HRQoL on all questions on one domain were categorized as having “good” HRQoL. They were otherwise categorized as having “poor” HRQoL. The results of the SF-36 domains at the one-year follow-up were adjusted for age, sex, education, marital status, comorbidities, view of life, fear of recurrence, T- and N-status, and the corresponding SF-36 domain at diagnosis. Logistic regression models were used to assess associations in forms of odds ratios (OR) and confidence intervals (CI) between good and poor HRQoL levels. Missing responses were treated according to the SF-36 software (maximum data recovery). The statistical software Stata v12.1 (Stata Corp., College Station, TX) was used for all analyses.

Results

Patient characteristics

Of the 487 patients eligible for the study, 349 (72%) answered the questionnaires at diagnosis. Non-responders at diagnosis were younger than the responders (43 vs. 51 years; p = 0.03), with no difference in the proportion between men and women (p = 0.83). A total of 250 (72%) responders had at least one year of follow-up, and of those, 235 (94%) returned both questionnaires. Those patients were included in the present study.

Of these 235 patients, the vast majority were women (n = 165; 70%), and the mean age was 51 years (range 18–88 years). During the first year of follow-up, 13 (6%) patients were diagnosed with loco-regional recurrences, another 10 (4%) developed distant metastases, and 5 (2%) had abnormal thyroglobulin values (Table 1).

TSH and HRQoL

TSH was measured at one year of follow-up. The majority (171 patients; 79%) had moderate or complete suppression (TSH <0.1). Additionally, 26 (9%) were mildly suppressed, and 19 (13%) had no suppression. On three SF-36 domains (PF, RP, and BP), patients on mild suppression had significantly worse HRQoL than patients with moderate/complete suppression and no suppression (p = 0.001–0.029). The statistical differences were also clinically significant (>10 points; Table 2).

Table 2.

HRQoL Measured with SF-36 in 235 DTC Patients in Three Groups Based on TSH Values One Year After Diagnosis

SF-36 domains	Moderate or complete suppression, TSH <0.1 ^a n = 171 (79%)	Mild suppression, TSH 0.1 to <0.4 ^a,b n = 26 (12%)	No suppression, TSH ≥0.4 ^a n = 19 (9%)	p-Value ^c
Physical functioning	85 [82–89]	74 [65–84]	86 [76–97]	0.026
Role physical	81 [78–85]	62 [50–74]	88 [78–98]	0.001
Bodily pain	83 [80–87]	70 [58–81]	88 [77–98]	0.029
General health	65 [61–68]	56 [48–64]	63 [54–73]	0.111
Vitality	57 [53–61]	46 [34–58]	55 [44–67]	0.072
Social functioning	80 [76–84]	71 [59–82]	83 [72–94]	0.172
Role emotional	81 [78–85]	69 [55–83]	87 [76–98]	0.153
Mental health	72 [69–75]	62 [52–72]	73 [65–81]	0.102

Data shown are the mean [confidence interval].

Categorized according to American Thyroid Association guidelines.

Differences in SF-36 points printed in bold correspond to a minimum of small clinically significant differences, i.e. ≥5 points.

p-Value assessed with the Kruskal–Wallis test.

TSH, thyrotropin; SF-36, Short Form-36 Health Survey.

View of life and HRQoL

At diagnosis and at follow-up, 50 (23%) and 40 patients (18%), respectively, had a negative view of life. Eighteen had a negative view of life both at diagnosis and after one year. At diagnosis, patients with a negative view of life had a significantly lower HRQoL on all eight SF-36 domains compared to those having a positive or no change in view of life (p < 0.001–0.036). The differences were also clinically significant, with a difference of >10 points on all but one domain (PF). At the one-year follow-up, those with a negative view of life had a significantly lower HRQoL on all domains expect for PF (p < 0.001–0.010; >10 points of difference; Table 3).

Table 3.

Differences in HRQoL Measured with SF-36 Between DTC Patients Having Positive or no Change in View of Life Compared to Patients Having Negative View of Life and Between Patients Having No, Seldom, and Often Fear of Recurrence at Diagnosis and After One Year of Follow-Up

SF-36 domains	Positive or no change in view on life n = 171 (77%) at diagnosis; n = 183 (82%) at one-year follow-up	Negative view on life n = 50 (23%) at diagnosis ^a ; n = 40 (18%) at one-year follow-up n = 54 (25%) at diagnosis;	p-Value ^b	No fear of recurrence n = 71 (31%) at one-year follow-up	Seldom fear of recurrence n = 98 (44%) at diagnosis ^a ; n = 105 (46%) at one-year follow-up	Often fear of recurrence n = 69 (31%) at diagnosis ^a ; n = 52 (23%) at one-year follow-up	p-Value ^c
Physical functioning
At diagnosis	84 [81–87]	79 [73–85]	0.036	83 [78–89]	85 [81–89]	81 [75–86]	0.341
At one-year follow-up	86 [83–88]	79 [70–87]	0.086	85 [79–90]	87 [84–91]	77 [71–84]	0.012
Role physical
At diagnosis	73 [69–77]	61 [54–69]	0.004	75 [68–83]	72 [67–78]	66 [59–72]	0.075
At one-year follow-up	82 [79–86]	67 [58–77]	<0.001	82 [76–89]	82 [77–87]	70 [63–78]	0.002
Bodily pain
At diagnosis	78 [75–82]	66 [58–73]	0.002	80 [74–87]	74 [69–80]	75 [69–81]	0.419
At one-year follow-up	83 [79–86]	72 [63–81]	0.010	82 [77–88]	82 [78–87]	75 [68–83]	0.153
General health
At diagnosis	68 [64–71]	50 [44–56]	<0.001	73 [68–77]	64 [60–68]	56 [50–62]	<0.001
At one-year follow-up	67 [64–70]	48 [41–54]	<0.001	69 [64–74]	66 [61–70]	52 [46–58]	<0.001
Vitality
At diagnosis	52 [48–56]	35 [29–40]	<0.001	56 [49–64]	50 [49–64]	40 [34–46]	0.004
At one-year follow-up	58 [54–62]	41 [33–48]	<0.001	61 [55–66]	58 [53–63]	41 [34–48]	<0.001
Social functioning
At diagnosis	72 [68–76]	55 [49–61]	<0.001	79 [73–86]	69 [64–74]	60 [54–66]	<0.001
At one-year follow-up	82 [78–85]	63 [53–72]	<0.001	82 [76–88]	81 [77–86]	67 [59–75]	0.002
Role emotional
At diagnosis	77 [73–80]	54 [45–63]	<0.001	83 [77–90]	73 [67–78]	64 [57–71]	<0.001
At one-year follow-up	84 [81–88]	64 [54–73]	<0.001	83 [77–89]	83 [79–88]	70 [62–77]	<0.001
Mental health
At diagnosis	68 [65–72]	52 [47–57]	<0.001	77 [55–20]	65 [61–69]	55 [50–60]	<0.001
At one-year follow-up	75 [72–77]	54 [48–61]	<0.001	76 [71–80]	73 [70–77]	60 [54–66]	<0.001

Data shown are the mean [confidence interval].

Differences in SF-36 points printed in bold correspond to a minimum of small clinically significant differences, i.e. ≥5 points.

p-Value measured with the Mann–Whitney U-test.

p-Value measured with the Kruskal–Wallis test.

Fear of recurrence, actual recurrence, and HRQoL

At diagnosis, 31% patients reported having a fear of recurrence “often” and 44% “seldom.” At the one-year follow-up, the corresponding figures were 23% and 46%, respectively. Those who reported a fear of recurrence as a frequent problem (“often”), either at diagnosis or after one year, had a HRQoL significantly and clinically lower for five and seven domains, respectively (p = 0.012–0.001; >5 points of difference; Table 3).

After one year, 28 (12%) patients had been diagnosed with a recurrence as an abnormal thyroglobulin, a loco-regional recurrence, or with distant metastases. These patients had a significantly lower HRQoL on seven of eight SF-36 domains (p = 0.046–0.003; >5 points of difference; Table 4).

Table 4.

HRQoL in Patients with Known Recurrence in DTC Patients Compared to Patients Without Recurrence at One-Year Follow-Up Measured with SF-36

SF-36 domains	No recurrence, n = 207 (88%)	Recurrence, ^a,b n = 28 (12%)	p-Value ^c
Physical functioning	85 [83–88]	73 [62–83]	0.008
Role physical	81 [78–85]	65 [53–77]	0.003
Bodily pain	82 [79–85]	73 [63–83]	0.046
General health	65 [62–68]	51 [42–61]	0.007
Vitality	56 [53–60]	47 [37–57]	0.060
Social functioning	80 [77–84]	65 [53–60]	0.003
Role emotional	82 [78–85]	69 [57–81]	0.029
Mental health	72 [69–74]	64 [69–75]	0.042

Data shown are the mean [confidence interval].

Recurrence: loco-regional recurrence, distant metastases, and/or abnormal Tg.

Differences in SF-36 points printed in bold correspond to a minimum of small clinically significant differences, i.e. ≥5 points.

p-Values measured with the Mann–Whitney U-test.

HRQoL at one year of follow-up

HRQoL was compared between diagnosis and after one year of follow-up. At one year, the SF-36 scores were significantly higher on six of eight SF-36 domains (p < 0.001; >5 points of difference) except for PF and GH (Table 5).

Table 5.

HRQoL Measured with SF-36 in 235 DTC Patients at Diagnosis Compared to HRQOL After One Year of Follow-Up

SF-36 domains	HRQoL at diagnosis	HRQoL after one year ^a	p-Value ^b
Physical functioning	82 [80–85]	84 [81–87]	0.078
Role physical	70 [66–73]	79 [76–83]	<0.001
Bodily pain	75 [72–79]	81 [78–84]	<0.001
General health	63 [60–66]	63 [60–66]	0.870
Vitality	48 [45–52]	55 [52–58]	<0.001
Social functioning	68 [65–71]	79 [75–82]	<0.001
Role emotional	72 [68–75]	80 [77–84]	<0.001
Mental health	64 [62–67]	71 [68–74]	<0.001

Data shown are the mean [confidence interval].

Differences in SF-36 points printed in bold correspond to minimum of small clinically significant differences, i.e. ≥5 points.

p-Values measured with Wilcoxon signed-rank test.

Predictive factors affecting HRQoL at one year of follow-up

Age >50 years, lower education, living alone, comorbidities, a negative view of life, and fear of recurrence at diagnosis were associated with a decreased HRQoL at one year of follow-up on some domains in bivariate analyses (p < 0.05). For each SF-36 domain, there was a strong correlation between HRQoL at diagnosis and HRQoL at one year of follow-up (p < 0.01). In the subsequent multivariate analyses, only lower HRQoL at diagnosis was a predictive factor of poor HRQoL at the one-year follow-up for each respective SF-36 domain (p < 0.01; Table 6).

Table 6.

Associations Between Patient and Tumor Characteristics and HRQoL Measured with SF-36 at Diagnosis and SF-36 Measured One Year After Diagnosis to Assess Factors at Diagnosis Predictive of SF-36 at One-Year of Follow-Up in 235 DTC Patients

		SF-36 domains at one-year of follow-up ^b
		Physical functioning	Role physical	Bodily pain	General health	Vitality	Social functioning	Role emotional	Mental health
Sex
Female		REF 1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0
Male	Crude OR [CI]; adjusted OR^a [CI]	0.87 [0.49–1.54]; 1.24 [0.56–2.75]	0.70 [0.38–1.29]; 0.95 [0.41–2.19]	0.55 [0.26–1.17]; 0.66 [0.26–1.66]	1.44 [0.75–2.76]; 3.46^** [1.38–8.68]	1.0 [0.52–1.95]; 2.38 [1.00–5.68]	0.64 [0.34–1.19]; 0.98 [0.45–2.14]	1.19 [0.65–2.17]; 2.04 [0.91–4.57]	0.93 [0.52–1.65]; 2.50^* [1.12–5.57]
Age
18–49		REF 1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0
50–88	Crude OR [CI]; adjusted OR^a [CI]	2.52^** [1.47–4.33]; 1.35 [0.61–2.99]	1.40 [0.81–2.40]; 1.36 [0.58–3.18]	2.09^* [1.09–4.02]; 2.22 [0.82–6.07]	1.34 [0.75–2.38]; 0.61 [0.24–1.60]	0.57 [0.31–1.07]; 0.61 [0.24–1.57]	0.80 [0.46–1.38]; 0.90 [0.40–2.04]	0.84 [0.48–1.47]; 0.84 [0.37–1.91]	0.81 [0.48–1.37]; 1.48 [0.62–3.53]
Education
Low		REF 1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0
Medium	Crude OR [CI]; adjusted OR [CI]^a	0.44 [0.17–1.13]; 1.01 [0.30–3.47]	0.42^* [0.19–0.94]; 0.39 [0.14–1.12]	0.75 [0.31–1.79]; 1.03 [0.32–3.28]	0.36 [0.13–1.03]; 0.32 [0.08–1.23]	1.19 [0.48–2.99]; 1.45 [0.45–4.67]	0.67 [0.29–1.55]; 0.34 [0.12–0.98]	0.71 [0.31–1.63]; 0.63 [0.22–1.85]	0.92 [0.40–2.09]; 0.49 [0.16–1.49]
High	Crude OR [CI]; adjusted OR^a [CI]	0.26^** [0.11–0.65]; 0.77 [0.23–2.52]	0.27^ [0.12–0.60]; 0.24^ [0.08–0.67]	0.35 [0.14–0.85]; 0.54 [0.16–1.86]	0.41 [0.15–1.14]; 0.70 [0.20–2.43]	1.31 [0.54–3.16]; 1.41 [0.43–4.55]	0.79 [0.36–1.74]; 0.50 [0.18–1.40]	0.50 [0.22–1.11]; 0.37 [0.12–1.12]	1.01 [0.46–2.22]; 0.84 [0.29–2.47]
Marital status
Married		REF 1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0
Living alone	Crude OR [CI]; adjusted OR^a [CI]	3.07^** [1.55–6.07]; 2.42 [0.98–5.99]	2.44^** [1.33–4.46]; 1.60 [0.71–3.65]	1.65 [0.83–3.29]; 1.01 [0.39–2.63]	3.17 [1.41–7.11]; 6.17^** [2.00–19.09]	1.58 [0.73–3.38]; 1.69 [0.60–4.78]	2.29^** [1.24–4.22]; 1.76 [0.79–3.95]	2.22 [1.20–4.12]; 1.75 [0.76–4.04]	1.74 [0.92–3.31]; 1.94 [0.81–4.66]
Comorbidities
0		REF 1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0
1	Crude OR [CI]; adjusted OR^a [CI]	2.03^* [1.11–3.75]; 1.75 [0.77–4.00]	1.00 [0.52–1.92]; 1.04 [0.44–2.46]	2.19 [0.98–4.89]; 1.77 [0.65–4.81]	1.72 [0.88–3.36]; 1.96 [0.75–5.14]	1.02 [0.51–2.05]; 1.26 [0.49–3.25]	1.02 [0.53–1.94]; 1.25 [0.56–2.81]	1.00 [0.52–1.92]; 1.36 [0.60–3.05]	0.71 [0.39–1.31]; 0.65 [0.28–1.49]
≥2	Crude OR [CI]; adjusted OR^a [CI]	9.22^** [3.64–23.31]; 3.30^* [1.07–10.21]	2.33^* [1.18–4.60]; 1.09 [0.41–2.91]	4.48 [1.99–10.07]; 1.49 [0.48–4.67]	2.59 [1.14–5.86]; 0.70 [0.20–2.43]	1.46 [0.63–3.40]; 1.19 [0.37–3.86]	1.39 [0.69–2.79]; 0.56 [0.20–1.58]	1.17 [0.57–2.37]; 0.67 [0.24–1.90]	1.14 [0.56–2.29]; 0.66 [0.23–1.91]
View of life
Positive/no change		REF 1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0
Negative	Crude OR [CI]; adjusted OR^a [CI]	1.21 [0.87–1.69]; 1.03 [0.67–1.60]	1.10 [0.79–1.53]; 0.83 [0.54–1.27]	1.39 [0.97–1.99]; 1.15 [0.72–1.85]	2.12 [1.30–3.46]; 1.52 [0.82–2.80]	2.14 [1.25–3.66]; 1.36 [0.74–2.51]	1.49^* (1.07–2.05]; 1.12 [0.75–1.66]	1.34 [0.96–1.86]; 0.94 [0.61–1.45]	2.88 [1.77–4.68]; 2.44^** [1.37–4.36]
Fear of recurrence
No		REF 1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0
Yes	Crude OR [CI]; adjusted OR^a [CI]	0.95 [0.51–1.78]; 1.09 [0.48–2.46]	1.55 [0.78–3.08]; 2.29 [0.92–5.72]	0.84 [0.40–1.77]; 0.67 [0.25–1.80]	2.02^* [1.05–3.88]; 1.36 [0.60–3.29]	1.83 [0.92–3.65]; 1.05 [0.43–2.57]	1.08 [0.55–2.13]; 0.64 [0.28–1.48]	1.66 [0.81–3.41]; 1.23 [0.51–2.95]	2.63^** [1.40–4.95]; 1.46 [0.64–3.35]
T status
0, 1a, 1b		REF 1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0
2	Crude OR [CI]; adjusted OR^a [CI]	0.91 [0.47–1.76]; 0.76 [0.32–1.87]	1.32 [0.67–2.57]; 1.16 [0.50–2.72]	1.09 [0.50–2.42]; 1.22 [0.43–3.44]	1.04 [0.49–2.19]; 1.33 [0.47–3.83]	0.83 [0.37–1.85]; 0.85 [0.30–2.39]	1.34 [0.68–2.64]; 1.66 [0.72–3.87]	1.19 [0.60–2.34]; 1.05 [0.45–2.47]	0.80 [0.40–1.58]; 0.86 [0.34–2.14]
3,4	Crude OR [CI]; adjusted OR^a [CI]	1.10 [0.58–2.07]; 1.91 [0.39–2.11]	0.80 [0.41–1.55]; 0.76 [0.33–1.85]	0.94 [0.43–2.04]; 1.48 [0.52–4.24]	0.68 [0.49–1.34]; 0.71 [0.29–1.77]	0.61 [0.29–1.28]; 1.00 [0.39–2.53]	0.83 [0.42–1.63]; 1.16 [0.50–2.65]	0.66 [0.33–1.31]; 0.70 [0.30–1.62]	0.50^* [0.26–0.95]; 0.59 [0.26–1.34]
N status
N0		REF 1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0
N1	Crude OR [CI]; adjusted OR^a [CI]	0.95 [0.56–1.61]; 1.63 [0.77–3.41]	0.94 [0.55–1.62]; 0.94 [0.44–2.06]	0.62 [0.32–1.20]; 0.79 [0.32–1.96]	0.55^* [0.31–0.99]; 0.40^* [0.17–0.96]	0.85 [0.46–1.57]; 0.77 [0.34–1.75]	0.83 [0.47–1.44]; 1.08 [0.51–2.27]	0.91 [0.52–1.60]; 1.08 [0.51–2.28]	0.81 [0.47–1.37]; 1.22 [0.58–2.58]
Corresponding SF-36-domain at diagnosis ^c
SF-36 domain	Crude OR [CI]; adjusted OR^a [CI]	0.90^ [0.87–0.93]; 0.90^ [0.87–0.94]	0.96^ [0.95–0.97]; 0.96^ [0.95–0.97]	0.95^ [0.94–0.97]; 0.96^ [0.94–0.97]	0.93^ [0.91–0.95]; 0.92^ [0.90–0.95]	0.94^ [0.93–0.96]; 0.94^ [0.92–0.96]	0.96^ [0.95–0.98]; 0.96^ [0.95–0.98]	0.97^ [0.96–0.98]; 0.97^ [0.95–0.98]	0.94^ [0.92–0.95]; 0.94^ [0.92–0.96]

Multivariate model adjusting for sex, age (two groups: 18–49 and 50–-88), sex, education (three groups: low, medium, high), marital status (two groups: married, living alone), comorbidities (three groups: none, one, or ≥2), view of life (two groups: positive/no change, negative), fear of recurrence (two groups: no, yes), T-status (three groups: T0/T1, T2, T3/T4), N-status (two groups: N0, N1) and the same SF-36 domain as at diagnosis.

The responses to SF-36 were dichotomized into “good” and “poor.” Good HRQoL = patients answering “no” or “little” symptoms/impact on HRQoL on all questions in one domain. Otherwise poor HRQoL.

For every step the SF-36 domain is increasing there is a lower risk for the patients to belong to the poor group regarding HRQoL.

p < 0.05; ^** p < 0.01.

CI, confidence interval; OR, odds ratio.

Discussion

This prospective, population-based study demonstrated that HRQoL in thyroid cancer patients improved from diagnosis to one year of follow-up. Additionally, it showed that view of life and fear of recurrence had a negative effect on HRQoL. Interestingly, TSH suppression did not seem to affect HRQoL in a linear way.

TSH suppression

TSH suppression has been suggested to be one reason why DTC patients have a lower HRQoL compared to the general population (23) and, moreover, a cause for symptoms often described by thyroid cancer patients (24). This study shows that patients with TSH <0.1 mIU/L had a better HRQoL than those with mild suppression, and similar scores compared to patients with no suppression. This is in agreement with previous studies, revealing no clear-cut association between HRQoL and different measures of thyroid hormones (25). In addition, restoration to normal TSH levels has not shown an increase in HRQoL (15). On the other hand, patients with a mild suppression might partly be those who had pronounced symptoms from complete TSH suppression. They may have been prescribed lower doses of levothyroxine during the first year to decrease their symptoms.

View of life and fear of recurrence

A previous study demonstrated a relationship between personality characteristics and HRQoL, for example optimism and self-esteem were related to better HRQoL, while neuroticism was related to poorer HRQoL. In addition, vitality and social functioning were strongly correlated to personality (26). In the present study, a negative view of life was significantly correlated to poorer overall HRQoL, and those SF-36 domains mostly affected were GH, VT, SF, RE, and MH. These results cannot be explained by personality alone, as only 18/50 patients had a negative view of life on both occasions. Coping mechanisms may have played an important role in those patients who experienced changes in their view of life (27).

Fear of recurrence affects patients with all forms of cancer and is surprisingly prevalent in DTC patients, despite the longevity in patients with this disease (28), which is in good concordance with the present results. In addition, patients with a fear of recurrence had a significantly lower HRQoL compared to patients without a fear of recurrence. The reduction of fear of recurrence over time was in good agreement with other studies, although the data are conflicting (29).

DTC has been considered to be a “good cancer,” which, however, is not necessarily in congruence with patients' own perceptions (30,31). This might make the coping process more complicated and add to the fear of a recurrence. In addition, depression has been shown to be prevalent in DTC compared to other cancers (32). High levels of fear of recurrence might co-variate with increased levels of depression. There is, however, a lack of information regarding a correlation between depression and fear of recurrence.

HRQoL during follow-up

Increasing HRQoL over time in DTC patients has been shown in some previous studies (7,33). Similar results were found in this study. HRQoL increased significantly from diagnosis until the one-year follow-up. These results could be expected due to the timing of the first questionnaire, which was filled in between surgery and RAI treatment. To receive a cancer diagnosis is life changing (34) and is expected to affect HRQoL. The possible factors that might, however, improve HRQoL over time have not yet been fully understood.

Predictive factors of HRQoL during follow-up

Among all the factors studied in the regression models, the actual HRQoL domain at diagnosis was the best predictive factor for the same domain after one year, a finding that is corroborated by others (35). Previous studies have shown conflicting data according to which patient characteristics affect HRQoL. Women and younger patients have reported lower HRQoL (33), and it has also been negatively affected by comorbidities (36), which was confirmed in the univariate analyses. On the other hand, disease stage has not been associated with HRQoL (36). HRQoL in DTC patients seems to be lower compared to the general population (37), and thus the actual cancer diagnosis might be one of the most important factors affecting HRQoL in DTC.

Methodological aspects

Methodological strengths of the study include the prospective and nationwide population-based design, which allowed the collection of detailed clinical data and adjustment for several confounding factors. The HRQoL questionnaire SF-36 used in the study has previously been regarded as appropriate, since it is considered to be a sensitive instrument when measuring HRQoL in thyroid cancer patients (38). However, SF-36 might not capture all aspects of HRQoL in DTC. The inclusion of a study-specific questionnaire was therefore regarded as a reasonable complement to capture important aspects regarding fear of recurrence and view of life in DTC patients, as there was no validated, disease-specific, questionnaire available in Swedish at the beginning of the study.

A methodological weakness is that the hospitals including patients did not start inclusion at the same time. Thus, not all eligible patients during the time period were included. However, patients were included from all Swedish hospitals administering RAI treatment to DTC patients, all disease stages, different age groups, and patients from both cities and rural areas. No presurgical HRQoL data were available, which made the follow-up data more difficult to interpret.

Conclusion

Even if DTC is generally associated with a good prognosis, in this study, HRQoL was substantially affected at the time of diagnosis, with some improvements at the one-year follow-up. Interestingly, TSH suppression did not seem to affect HRQoL to a large extent. As fear of recurrence and a negative view of life substantially affect HRQoL, DTC patients should be given additional attention in order to improve their HRQoL.

Footnotes

Acknowledgments

This study was supported by grants from The Cancer Research Foundations of Radiumhemmet, The Swedish Medical Association, Serafimerlasarettet Foundation, Stockholm County Council, Stiftelsen för Kirurgiskt Samarbete, and the Capio Research Foundation.

The manuscript was proofread by David Boniface. Statistical support was provided by Johan Bring. Investigators including patients: Helene Hörberg, Mälarsjukhuset Eskilstuna; Maria Annerbo, County Hospital Falun; Åsa Bergström Morelius, County Hospital Gävle; Johanna Svensson, Sahlgrenska University Hospital; Viveka Bergman, Linköping University Hospital; Åsa Harnesk, Karlstad Central Hospital; Pernilla Asp, Skåne University Hospital; Petra Flygare, County Hospital Sundsvall; Maria Sandström, University Hospital of Umeå; Tanweera Khan, Uppsala University Hospital; Karin Hubertsson, Västerås Central Hospital; and Kristina Engström, Örebro University Hospital.

Author Disclosure Statement

No competing financial interests exist.

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