To the best of our knowledge, this study is the first to evaluate the association between sarcopenia and fatigue in middle-aged Asian cancer survivors, and we found sarcopenia was associated with severe fatigue, especially in male survivors and pre-menopausal female survivors.
A Japanese study, of which more than 75% of the subjects were female, found no relation between muscle strength and fatigue in comparisons of cancer survivors and healthy participants [6]. A cross-sectional study of Latin Americans including mainly elder people (mean age was 76 for the sarcopenic participants and 70 for the participants without sarcopenia) also concluded that sarcopenia and fatigue were not associated [17]. In a cross-sectional study of European advanced cancer patients (mean age 64), there was no significant association between higher muscle mass and lower fatigue levels in females [16].
However, some studies have shown strong association between low skeletal muscle mass and fatigue, similarly to the findings of this study. A study on Norwegian cancer patients (mean age 65) with advanced (stage IIIB-IV) non-small cell lung cancer, low skeletal muscle index (SMI) was significantly associated with high fatigue in the male cancer patients [14]. A cross-sectional study of Chinese cancer patients (older than age 18) also found that cancer-related fatigue increased dramatically when sarcopenia was severe [15]. These two studies included advanced cancer patients over stage III and skeletal muscle mass was measured by CT scan.
Several studies have reported that exercise could reduce fatigue of cancer patients [29–31]. Studies revealed that starting exercise programs before cancer treatment can effectively reduce fatigue level as well as improve cancer treatment outcomes [31–34]. Although the underlying mechanism has not been clarified, the positive effect of exercise on the psychological status, cardiopulmonary function, and muscle system may explain the beneficial effects of exercise in cancer patients. Additionally, exercise was found to increase muscle protein synthesis, muscle mass, slow muscle depletion, and improve muscle strength [35]. Thus, it could be possible that sarcopenic persons less involved in physical exercise are less likely to take an advantage of exercise-related health benefits, which may result in higher prevalence of fatigue among them. In this study, although statistical significance was lacking, survivors with sarcopenia tended to be less involved with an adequate level of exercise. Interestingly this study found that significant inverse association between sarcopenia and fatigue persists even after adjusting for the exercise level. Although further study is necessary, this finding may suggest a biological mechanism directly underlying the association between sarcopenia and fatigue.
In a review of 28 studies published January 1950-March, 2014, the prevalence of sarcopenia in cancer patients was 14%-78.7% [36]. In the past, the diagnosis of sarcopenia had been applicable only for the elderly, thus, studies on sarcopenia had been conducted mostly in the elderly population [16, 17]. The prevalence of sarcopenia among cancer survivors has been reported to widely vary. The various sarcopenia prevalence between studies may be attributable to the diverse demographic characteristics of the study population such as age and sex. However, the new revised definition of sarcopenia suggests that sarcopenia begins earlier in life regardless of age [18]. Afterwards, several studies have investigated the prevalence and related factors of sarcopenia of the middle-aged population [37, 38].
In this study of middle-aged cancer survivors, the prevalence of sarcopenia was 15% in males and 20% in females, which was much lower than the prevalence observed in other Korean studies (34% in males and 33% in females) [39]. We think that this discrepancy might be caused by the different age distribution between the two Korean cancer survivor studies.
The prevalence of fatigue has also been known to vary by the influence of several factors. A study reported that approximately 45% of cancer survivors experienced fatigue during cancer treatment and was reduced to approximately 29% after the completion of cancer treatment [3]. The prevalence of fatigue after the completion of cancer treatment in the previous study is similar to the fatigue prevalence observed in this study. Female cancer patients are more likely to report fatigue than male patients, consistent with the finding of this study that fatigue prevalence was lower in male cancer survivors (22%) than that in female cancer survivors (32%). Cancer type may also affect fatigue levels. Breast and colorectal cancer survivors were known to complain more about fatigue than prostate cancer survivors [11]. In a Korean study, the prevalence of fatigue was 66% in disease-free breast cancer survivors [40]. Fatigue prevalence tended to be especially higher when cancer patients had received additional treatment such as radiation therapy, chemotherapy, or hormone therapy compared to when they had received surgical treatment only. The study conducted only for breast cancer survivors showed that the cancer stage was associated with fatigue [41]. The relatively low prevalence of fatigue shown in our study compared to the prevalence in previous studies may be because cancer survivors with an early stage of cancer (Stage I) accounted for more than 50% of the participants in our study.
The present study has limitations to be considered. First, study participants were recruited from a survivorship clinic of an academic hospital in Korea, which may limit generalization of study findings to all cancer survivors. Second, this study could not apply comprehensive sarcopenia which includes muscle strength and physical performance level because of the lack of data. We identified a sarcopenic person based on skeletal muscle mass for this study, given that loss of muscle mass may well reflect deteriorating physical function [35]. Third, we measured fatigue level using the FSS which is a reliable and validated tool for assessing fatigue in the general population [24, 25], instead of the Brief Fatigue Inventory (BFI) which may be more commonly used for cancer survivors [42]. Fourth, the innate problem of cross-sectional design of this study made it difficult to clearly understand the cause-effect relationship between sarcopenia and fatigue.