In this study, we examined whether muscle depletion, i.e., loss of muscle mass or muscle strength, in patients receiving palliative care is related to prognosis. We retrospectively examined the data obtained in daily clinical practice among patients with various types of cancer who were supported by a palliative care team at a university hospital. A significant association between PMI, which was employed as an indicator of muscle mass, and survival was found. PGS, which was used as a muscle strength index, also was significantly associated with survival. These results suggest that muscle mass and strength in palliative care patients decline as their status deteriorates and that muscle depletion is associated with prognosis. Hence, our study shows that muscle depletion is a potential prognostic parameter.
PMI, which is a measure of muscle mass, was an independent prognostic factor in palliative care patients. PMI measurement has been widely used as an alternative method for evaluating all major skeletal muscles at the lumbar level, and PMI has been associated with prognosis in patients with cancer [22, 23] and with surgical outcomes . However, the previous studies have examined patients receiving anticancer therapy with a prognosis of more than several months. In a recent systematic review, Wiegert et al.  reported the association between low muscle mass and survival in patients with incurable cancer and identified that only two [26, 27] of 13 studies had shown low muscle mass as a significant independent predictor of survival in a multivariable analysis; they concluded that the evidence of the association between low muscle mass and survival in patients with incurable cancer is insufficient. Moreover, in the review, the methods for muscle mass evaluation, patient age, type of cancer, and definition of low muscle mass varied across the studies. Thus, further studies may be needed to clarify these factors. In addition, previously reported median OS for incurable cancer ranged from 130 days  to 32.3 months . In our study, the median OS was 78.5 days, suggesting that more terminally ill patients are included in our investigation, which in turn had a significant effect on our results. No other study that examined the association between muscle mass and prognosis in a cohort with a high proportion of terminally ill patients has been conducted.
PGS was also an independent prognostic factor in palliative care patients. In the evaluation of muscle strength in patients with cancer, hand grip strength measurement has been widely used as a standard approach . Previous studies showed that reduced hand grip strength is associated with worse prognosis [31, 32] and poor treatment outcome [33, 34]. However, these studies involved patients with cancer with a longer prognosis who are receiving anticancer treatment. Thus, the relationship between muscular strength and prognosis in palliative care patients whose prognosis is within several months has not been reported. Our study clarified such relationship using PGS as an index of muscle strength. Majority of the patients had PS 3 or 4, with a significantly reduced physical function. PGS is useful in assessing muscle strength in patients with limited physical function [18, 35], and its invasiveness is minimal. Hence, PGS measurement was considered to be a feasible procedure for muscle strength assessment in palliative care patients.
In our study, when comparing sex-stratified survival rates by median PMI and PGS, the differences in prognosis were more pronounced in men than in women. This may reflect sex differences in muscle depletion. Wallengren et al. examined the changes in muscle mass using dual-energy X-ray absorptiometry scans that were performed 2 years before the death of 471 palliative care patients  and reported sex differences. In their study, the males had clear muscle mass loss at the end of life, which was not observed in females. Various hormones, cytokines, and the immune system are associated with cachexia progression and muscle depletion [37, 38] and are considered vital factors that cause sex differences. Elucidation of the mechanism of the sex difference is one of the keys to measures for muscle depletion and requires further investigation.
Furthermore, our study suggests that PMI or PGS could be a parameter for prognostic prediction. The parameters used in this study, i.e., edema, albumin levels, and PS, have also been adopted in several prognostic tools . Although PS, which reflects physical functions, has been employed as a parameter , no tool included muscle depletion . PMI and PGS may be promising parameters for a more accurate prognostic prediction in palliative care patients.
This retrospective study has some limitations. Patients without PGS measurement and CT scans were excluded from the analysis, which in turn possibly resulted in selection bias. Moreover, the PGS values analyzed in this study were obtained from daily clinical practice and thus may not have been measured in a strict manner. Hence, prospective and validation studies involving larger palliative care populations are warranted.