Introduction
Worldwide, 40–50% of all newly diagnosed cancer survivors are of working age and therefore, potentially part of the labor force [
1,
2]. Overall, the percentage of cancer survivors able to return to work is 63.5% (range 24–94%) [
3]. Despite advances in early detection and cancer treatment for cancer survivors of working age, cancer and its treatment can still result in a wide range of long-term physical and psychological problems, including fatigue, depression, and cognitive symptoms [
4,
5]. Cognitive symptoms are frequently reported to affect cancer survivors’ functioning at work [
6], and adverse consequences of even subtle cognitive symptoms may be profound. The findings of an integrative review suggest that cognitive symptoms are an essential factor for work ability, return to work, and work performance [
6]. A recent cross-sectional study demonstrated that cognitive symptoms at work were associated with lower levels of quality, quantity, and timeliness of completed work among breast cancer survivors [
7]. Patients who are cognitively affected may experience challenges on the job, especially in jobs that require peak performance in assimilating, processing, retaining, and utilizing information [
8,
9]. The cognitive domains most likely to be negatively impacted are working memory and executive function [
10]. Memory problems may influence a workers’ capacity to acquire the knowledge and skills necessary to carry out work-related functions [
11] and executive function problems may diminish the planning and implementing of strategies. Optimal cognitive functioning is required in many non-manual (e.g., office work), and also in manual (e.g., construction work) occupations [
12].
Cancer-related cognitive impairment (CRCI) is an important and prevalent problem for survivors, which can result from chemotherapy [
13], but has also been associated with radiotherapy and surgery [
10,
14]. Although several studies have assessed CRCI in a range of cancer populations, via neuropsychological testing and self-report assessments, there is a lack of longitudinal research examining occupationally active cancer survivors, and the cognitive symptoms they are dealing with while at work. In a previous study, Dorland et al. (2017) showed that working cancer survivors experienced more memory symptoms compared with executive function symptoms [
15]. These symptoms persisted during 18 months follow-up. Assessing the survivor’s personal judgment of her/his ability to complete tasks in daily life is an important aspect of CRCI. The assessment provides insight into environmental and contextual factors that may facilitate or hinder performance.
Cognitive symptoms in the general population of cancer survivors (excluding central nervous system cancer) have mostly been attributed to the neurotoxic effects of chemotherapy [
16,
17]. For example, Janelsins et al. (2018) showed that breast cancer patients had significantly worse cognitive symptoms from prechemotherapy to postchemotherapy and from prechemotherapy to 6-month follow-up and compared with healthy controls [
18]. Particularly, cancer survivors treated with chemotherapy often report memory loss and executive dysfunction [
13]. Although chemotherapy is a risk factor for developing CRCI, it is clearly not the only factor associated with this kind of impairment. Surgery [
19,
20], other adjuvant therapies [
21‐
23], and the cancer itself [
3] may also lead to impairments due to an inflammatory response triggering neurotoxic cytokines. Further, CRCI has also been associated with psychological consequences of cancer and its treatment, including depression and fatigue [
10,
14].
To date, no studies have examined the association between type of cancer treatment and self-reported cognitive symptoms in working cancer survivors, using a longitudinal study design. Understanding the association will be a valuable resource for occupationally active survivors’ health care providers in terms of treatment plans and guidance. Therefore, in the current study, we aimed to assess: [
1] the longitudinal associations between type of cancer treatment and self-reported cognitive symptoms (memory and executive function) in working cancer survivors, and [
2] to assess whether the course of cognitive symptoms over 18 months post return to work differed per treatment group. In previous studies, cognitive impairment in cancer patients has mostly been attributed to the neurotoxic effects of chemotherapy. Given this biomechanical explanation [
8,
24], it is hypothesized that cognitive symptoms are more frequently present in cancer survivors who received chemotherapy than in cancer survivors who only received locoregional treatment (surgery and/or radiotherapy).
Discussion
This study is, to the best of our knowledge, the first longitudinal study to examine type of cancer treatment and cognitive symptoms in working cancer survivors. Cancer survivors who received chemotherapy and cancer survivors who received locoregional treatment had comparable levels of memory symptom scores. The level of symptoms regarding executive function was significantly lower for cancer survivors who received chemotherapy, compared with those receiving locoregional treatment. Cancer survivors who received other systemic therapy reported more symptoms in memory and executive function, compared with those receiving locoregional treatment. In cancer survivors who received other systemic therapy, memory and executive function symptom scores increased over time compared with cancer survivors who received locoregional treatment. In cancer survivors who received chemotherapy, and cancer survivors who received locoregional treatment, memory and executive function symptom scores remained stable, but persistent, during the first 18 months after return to work.
Interpretation of the findings
In a previous review, including studies that followed cancer survivors up to 1–2 years post-treatment, it was shown that cognitive symptoms can arise during cancer treatment and can persist up to several years after completion of treatment [
13]. In line with these findings, this study showed that memory and executive function symptoms in cancer survivors were continuously present, during the first 18 months after return to work.
The finding that cancer survivors who receive chemotherapy, had comparable levels of memory symptoms and lower levels of executive function symptoms than cancer survivors who received locoregional treatment is not in line with previous studies. Previous studies show that chemotherapy is the main, albeit not the only driver of CRCI [
13]. It is important to consider that data derived from the self-reported CSC-W in WOLICA, might not be directly comparable to neuropsychological assessments. No longitudinal studies have used self-reported questionnaires to compare levels of cognitive symptoms in cancer survivors, treated with chemotherapy, to levels in those who received other treatments. Nevertheless, the finding that more intensively treated cancer survivors do not have more cognitive complaints, and have even lower symptoms, compared with those who received locoregional treatment is surprising. Moreover, Janelsins et al. (2017) showed that breast cancer patients had significantly higher self-reported cognitive symptoms from prechemotherapy to postchemotherapy as well as from prechemotherapy to 6-month follow-up [
18]. The current findings might be explained by the fact that this sample consisted of occupationally active cancer survivors, and that chemotherapy is negatively associated with return to work [
32,
33]. Notably, cancer survivors exposed to chemotherapy or a combination of therapies (e.g., surgery, radiotherapy, and chemotherapy) have a fourfold higher risk of not returning to work in the first (or even the three) year(s) following treatment, compared with cancer survivors who only had surgery or one type of treatment [
32]. In line with this, it can be reasoned that the cancer survivors in this study, who are exposed to chemotherapy and are currently working, may represent a high functioning subset of cancer survivors treated with chemotherapy.
It was further found that the course of cognitive symptoms differed per type of cancer treatment. Memory and executive function symptom scores increased over time in cancer survivors who received other systemic therapy compared with cancer survivors who received locoregional treatment. An explanation may be that in those who received other systemic therapy, 76% were still on active treatment at baseline. This percentage is much higher than the percentage of survivors on active treatment in those receiving chemotherapy or locoregional treatment. In addition, the sample size of this group is comparably small.
Strengths and limitations
A strength of this study is that a longitudinal design was used with repeated measurements of cognitive symptoms in working cancer survivors at baseline, 6, 12, and 18 months after return to work. Data of all four measurement points were available for the majority (81%) of participants. A validated measure of work-related cognitive symptoms was employed, i.e., the CSC-W [
10], and linked with objective data on clinical factors from the NCR. Differences between chemotherapy-treated and non-chemotherapy-treated patients that might impact the reporting of cognitive symptoms are accounted for, including sociodemographic factors, clinical and treatment-related factors, and psychological symptoms. However, some unmeasured confounding might be present to at least some degree.
Also, some limitations have to be acknowledged. While the CSC-W takes into account the work environment, a combination of both self-reported and performance-based measures, i.e., neuropsychological tests, would be preferable. The combination of both self-reported and performance-based measures would enable the investigation of the independent and combined contributions of self-reported and performance-based measures to the risk of work-related cognitive symptoms. Also, for the CSC-W, there are no cut-offs available, making it difficult to determine whether an individual’s symptom level of cognitive functioning is a clinically relevant sign. Another limitation might concern selection bias. Potential participants were identified and informed about the current study by their OP during a regular visit in the return to work process. Possibly, the sample might be biased towards patients who resumed work after cancer diagnosis and treatment with better cognitive functioning, while patients with poorer outcomes might be underrepresented. At baseline, one-third of cancer patients were still undergoing treatment. Although treatment completion at baseline was controlled for, we did not adjust for possible treatment completion during follow-up, as this information was not available at the time of the analyses. Because cognitive effects of hormone therapy for breast cancer and prostate cancer may occur, given the critical role of hormones in the brain [
13,
34], future studies may also control for when these individuals completed treatment.
Implications for practice and research
The findings may have implications for the management of cognitive symptoms of cancer survivors at work. Awareness that cognitive symptoms may persist after return to work should be increased in cancer patients, employers, colleagues, (occupational) health care professionals, and the society as a whole. Assessment of cognitive symptoms in working cancer patients is important to provide accurate information on the occurrence of cognitive symptoms in working cancer survivors, as well as assistance with symptom management. The findings may help to inform policy and practice to act upon cognitive limitations in working cancer survivors. Occupational health care practitioners, employers, general practitioners, policymakers and other relevant stakeholders should lay out priorities and target efforts to aid working cancer survivors. The CSC-W has been included in the Guideline “Cancer and Work” of the Netherlands Society of Occupational Medicine [
35] and this study may provide additional information for occupational physicians.
Because the reporting of cognitive symptoms may be rooted in part in psychological states such as depression and fatigue, future research should focus on the interrelation between treatment, cognitive functioning, and psychological symptoms. In addition, a combination of both self-reported and performance-based measures of cognitive functioning would be preferred, as studies based on neuropsychological assessment in working cancer survivors are lacking [
8]. Also, it would be informative to compare cancer survivors who returned to work to those who did not, with respect to their cognitive functioning.
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