Persistent quality of life impairments in differentiated thyroid cancer patients: results from a monitoring programme

In the present investigation we analysed the HRQOL of DTC patients after thyroidectomy undergoing RAA and RAIT and during follow-up using data from HRQOL monitoring in clinical routine. Such data have so far been scarce and provide valuable additional information to findings from clinical studies.

In a cross-sectional study we compared HRQOL scores in DTC patients at the time of their RAA with scores in the Austrian GP. In addition, we analysed longitudinal data up to 30 months after RAA and investigated the effects of histology (papillary vs. follicular), disease stage, method of TSH stimulation and time since RAA on HRQOL scores. The cumulative dose of ¹³¹I has shown to be a clinical predictor of HRQOL [25] but could not be included into our multivariate models as it was highly confounded by time from baseline. Thus, the effects of time since RAA could very well be attributable to this clinical variable, but statistically could not be assigned to either of them due to collinearity. In all analyses we adjusted for the effects of age and sex, i.e. the effects we found cannot be explained by the facts that women usually report worse HRQOL and that the majority of DTC patients are women.

In the cross-sectional comparison of HRQOL scores in DTC patients and the scores in the GP, patients reported worse HRQOL on almost all domains of the QLQ-C30. In particular, large differences were found for role functioning (25 points; comprising questions on the ability to perform usual work and leisure activities), fatigue (23 points), sleep disturbance (15 points), and global QOL (15 points; comprising questions on subjective global health state and QOL). Against our expectations from clinical experience, there was no overall impairment of cognitive functioning in patients. However, there was a significant difference in cognitive functioning between DTC patients and the GP, but in women only. A similar interaction effect was found for role functioning and social functioning (comprising questions on ability to participate in social activities and fulfil social roles) and appetite loss.

These results were not surprising insofar as all of our DTC patients in this treatment phase were in a hypothyroid state. It is well known that hypothyroidism causes a broad range of physical as well as psychological symptoms, such as constipation, weight gain, fatigue, depression and slowed cognition, and that associated distress is high [26, 27]. However, the magnitude of the effect was still striking as it is comparable to that in other cancer diagnoses which are usually considered much more impairing, such as laryngeal cancer [28]. Furthermore, our longitudinal analyses indicated that some issues were influenced by a hypothyroid state to the extent we had expected. Emotional functioning (comprising feelings of worry, anxiousness, nervousness and irritability) in our sample had improved to the level in the GP (defined as a difference <5 points) after 12 months, had worsened at 24 months, and had recovered again at 30 months, but without significant effect of the method of TSH stimulation. Similar fluctuations over time were observed for fatigue scores, which were significantly lower under exogenous TSH stimulation but without reaching the level in the GP level during the observation period. Likewise, role functioning did not reach the level in the GP level either over time or under exogenous TSH stimulation. However, in line with previous reports that exogenous TSH stimulation is associated with better HRQOL especially with regard to functioning (physical, social, role and emotional), sleep disturbance and fatigue [8, 29], our patients with endogenous TSH stimulation were also at risk of low HRQOL (on the domains physical, role, social and cognitive functioning, global QOL, fatigue, sleep disturbance and appetite loss). Yet the conclusion that HRQOL impairment is minor in DTC patients as long as they do not have to undergo hormone withdrawal [4] cannot be supported by the present data.

There are conflicting reports in the literature as to when a restored HRQOL can be expected. For example, Taieb et al. found that HROQL is restored shortly after surgery [30] and Crevenna et al. found significant improvements at 1 year after diagnosis and beyond [5]. Our results, on the one hand, showed significant improvements after 12 months for some domains. On the other hand, they also support reports of prolonged posttreatment fatigue in thyroid cancer patients and survivors [31]. Physiological explanations discussed are related to TSH suppression during posttreatment care. Fatigue might be a result of subclinical hyperthyroidism [32] which again possibly causes a permanent change in the autonomic nervous system [33]. It has also been suggested that the optimal preoperative TSH level might be different from the target value of TSH suppressive therapy [34]. Husson et al. found that fatigue in short-term and long-term survivors of thyroid cancer is strongly associated with thyroid-specific HRQOL, including sympathetic problems and emotional distress [35]. Our own data showed similar courses of fatigue and emotional distress over time. These results suggest that, aside from identifying physiological causes, the emotional aspect of fatigue might require more attention in the management of thyroid cancer patients as psychological coping mechanisms may play an important role here.

Our results on the comparison of patient scores and scores from the GP are largely in line with the results from a previous study on HRQOL in thyroid cancer patients during inpatient rehabilitation conducted in Germany [15]. The German study clearly showed larger differences between patients and the GP on QLQ-C30 domains. The scores differed from our data by >5 points, except for global QOL, nausea/vomiting, appetite loss, constipation and diarrhoea. In particular, cognitive and emotional problems, pain and financial difficulties were more pronounced in the German patient group (the scores differed from our data by ≥19 points). The fact that patients with higher disease burden are more likely to make use of inpatient rehabilitation could be one explanation for these large differences. In addition, rehabilitation prolongs absenteeism from work which might cause additional financial strain. It is also not unusual that psychosocial distress in particular is aggravated directly after completion of active therapy.

The impact of sex and age found in our sample is in line with previous reports [5, 15, 25, 36], as we also found more impairment in women than in men and decreasing scores with increasing age on a range of domains. Most of these effects were not disease-specific, but rather reflected sex and age differences that can also be observed in the GP. This is an important issue when interpreting such effects in patient samples [37]. In addition, disease-specific patterns of the impact of age were found for social functioning, pain and appetite loss. While scores in patients were significantly worse, their decline with age was less pronounced than in the GP.

Despite that the fact that our results were inherently consistent and bias assessment did not cause severe concern, the present analysis had some limitations that restrict the generalization of the findings. Firstly, in our samples the number of patients with follicular cancer type was about 10 % higher than in the GP. We did not, however, find an effect of histology in multivariate analysis, indicating that other factors were more strongly associated with HRQOL. Secondly, the number of patients in the monitoring programme decreased with time, and thus the results may have been biased by the selection of patients. However, there was no significant difference in stage of disease between earlier and later assessment time-points, and the majority of patients at the 30-month follow-up had received one or two cycles of RAIT. Thus, there is no indication that patients with more severe disease participated longer in HRQOL monitoring. Thirdly, there was an unbalanced distribution of assessments with exogenous and endogenous TSH stimulation which limited the validity of the results of comparisons between the two methods. Therefore, analyses including this factor were rerun but resulted in only minor changes in the remaining model parameters (results not shown).

Fourthly, the distribution of paper and pencil assessments and of electronic assessments suggest more missing data during the period of paper and pencil assessment. Therefore, we investigated the influence of the assessment method on HRQOL scores and found that older patients scored worse on cognitive functioning when assessed using the computer-based system (8 points difference). This finding may indicate some selection bias. A plausible explanation seems to be that the inclusion of patients in the HRQOL monitoring programme might have been affected by subjective factors. Clinical personnel who, since electronic assessment can immediately access a patient’s HRQOL scores and the information can be used in the communication with the patient, might have become increasingly motivated to include as many patients as possible. In addition, presentation of questions on a tablet computer might be advantageous for cognitively impaired patients as there are usually only two or three questions per page in a large font. Detailed analysis on the impact of assessment method on cognitive functioning in the entire monitoring sample is warranted.

It has also to be kept in mind that our Austrian reference data were collected in 2002 and values may have changed in the meantime. Also we cannot provide information on possible differences between Tyrolean and Austrian GP values, which if they do exist, would results in either overestimation or underestimation of thyroid cancer patients’ HRQOL impairment. Our reference values were, however, consistent with the EORTC QLQ reference values for the GP published in 2008 [38] and, thus, seem to be sufficiently sensitive. In addition, in a recent update of the German reference values for the QLQ-C30 from the year 2001 changes were small and not clinically relevant for most scales, except for fatigue, sleep disturbances and pain. These symptoms were more severe in the new GP sample, which according to the authors, may be attributed to a sampling bias [39].

In conclusion, our results provide further evidence that DTC patients’ burden from symptoms and functioning impairments is unrelated to the favourable clinical outcome. Nonetheless, thyroid cancer is still often labelled as the “good” cancer with only minor impairments so that patients may feel that their concerns are being trivialized and that they lack information and support [16, 40]. Psychosocial distress as well as persistent problems with fatigue and possibly resulting difficulties at work and during leisure time are frequently overlooked in clinical practice and often falsely attributed to hypothyroidism only. Thyroid cancer patients with HRQOL impairments which persist quite some time after treatment are not uncommon. This is important information for treating physicians, especially as the “average” thyroid cancer patient is usually seen by representatives of a range of different medical professions and there is rarely continuity of care during the treatment and follow-up process. Acknowledging thyroid cancer patients’ burden is essential in improving their care, especially when it comes to psychosocial issues. Finally, our results highlight the need for more systematic investigations of DTC patients HRQOL in order to provide patients with reliable information about what they need to expect when living with a DTC diagnosis and the sequelae of treatment.