Sarcopenia is a condition characterized by progressive and generalized loss of skeletal muscle mass and strength, leading to physical disability, poor quality of life (QoL), and increased mortality [1]. In patients with cancer, sarcopenia is caused by various factors, including the cancer itself, treatment-related adverse events, and reduced physical activity [2,3]. Sarcopenia in patients with cancer is associated with shorter survival, increased treatment-related toxicity, higher postoperative complications, reduced physical function, and decreased QoL [4-6].

The prevalence of sarcopenia in patients with cancer has been widely reported, with rates ranging from 11% to 74%, depending on the cancer type and stage [7]. In terminally ill patients with cancer, sarcopenia is nearly universal due to progressive catabolism and systemic inflammation [8]. Despite the well-established prognostic significance of sarcopenia in advanced cancer, evidence addressing sarcopenia, specifically in terminally ill patients, remains limited. In this review, we aim to investigate the clinical implications of sarcopenia in terminally ill patients with cancer, focusing on its impact on prognosis, functional decline, symptom burden, and QoL. Additionally, we discuss the diagnostic challenges and potential management of sarcopenia in this population.

Sarcopenia has been consistently identified as a strong prognostic factor in patients with cancer, with a greater impact in terminally ill patients. A prospective study investigating nutritional indices in terminally ill patients found that poor nutritional status was significantly associated with worse survival. Specifically, low triceps skinfold thickness was associated with a 2.9-fold increase in mortality risk [9]. Similarly, a prospective cohort study of 727 patients with terminal cancer showed that muscle power, assessed using the Medical Research Council scale, was a predictor of imminent death within a week of admission to hospice care. In the most accurate prediction model, lower mean muscle power was associated with an increased risk of imminent death within a week [10]. Another prospective observational study of 628 patients with advanced cancer in a palliative care outpatient unit reported that the phase angle measured by bioelectrical impedance analysis (BIA) was a key indicator for detecting sarcopenia and a significant predictor of shorter survival (hazard ratio, 2.3) [11]. A prospective observational study of 334 patients with advanced cancer in a palliative care unit assessed the relationship among sarcopenia, nutritional status, and overall survival using mid-upper arm muscle area (MUAMA), calf circumference (CC), and appendicular skeletal muscle mass. In this population, sarcopenia assessed using MUAMA (43 vs. 67 days) and CC (44 vs. 77 days) was significantly associated with shorter survival [12]. Additionally, a retrospective cohort study of 304 patients with cancer receiving palliative care evaluated the prognostic value of the Strength, Assistance with walking, Rise from a chair, Climb stairs, and Falls (SARC-F), a self-report questionnaire assessing muscle strength and physical function. The study found that patients with SARC-F scores ≥4 had significantly worse overall survival (40 vs. 121 days) [13]. Collectively, these studies have suggested the significant prognostic value of sarcopenia in terminally ill patients with cancer, as evaluated through various clinical, functional, and nutritional parameters.

Sarcopenia significantly contributes to the functional decline and deterioration of QoL in terminally ill patients with cancer. Progressive muscle wasting leads to reduced physical strength, impaired mobility, and increased risk of falls, ultimately resulting in greater dependence on caregivers. In this population, the impact of sarcopenia extends beyond physical limitations and affects psychological well-being, social interactions, and overall comfort during end-of-life care.

Several studies have demonstrated an association between sarcopenia and worsening physical function. A cross-sectional study of 135 patients with advanced cancer receiving home palliative care found that 77% had sarcopenia (SARC-F ≥4) and 68% were malnourished. Sarcopenia was found to be potentially associated with malnutrition [14]. A retrospective cohort study of 304 patients receiving palliative care found that those with higher SARC-F scores (≥4) experienced significantly greater difficulty in performing daily activities. Compared with patients with lower SARC-F scores (<4), those with SARC-F scores ≥4 were far more likely to have impaired strength (100% vs. 43.6%), require walking assistance (98.3% vs. 3.7%), struggle with rising from a chair (90.5% vs. 3.2%), and have difficulty climbing stairs (98.3% vs. 34.0%) [13]. In addition to impairing mobility and increasing dependence, sarcopenia exacerbates overall functional decline in terminally ill patients with cancer. A prospective study involving 1,660 patients with incurable cancer at the Palliative Care Unit of the Brazilian National Cancer Institute demonstrated that lower muscle mass and strength, assessed using MUAMA and handgrip strength (HGS), were strongly associated with worse performance status. Patients in the sarcopenia group had a median Karnofsky Performance Status of 40% compared with 60% in those with better muscle mass phenotypes. Notably, Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) scores, which reflect nutritional deterioration and symptom burden, also differed significantly according to sarcopenia severity and sex. Among men, those in the sarcopenia group had a median PG-SGA SF score of 15, compared with a score of 10 in those with better muscle mass phenotypes. Among women, the difference was even more pronounced, with PG-SGA SF scores of 21 in the sarcopenia group compared with a score of 13 in those with better muscle mass phenotypes [15].

Sarcopenia not only affects physical function but also significantly worsens QoL and symptom burden in patients receiving palliative care. A cross-sectional study of 770 patients with incurable cancer demonstrated that a worsening muscle mass phenotype, as assessed using the MUAMA and HGS, was strongly associated with declines in multiple QoL domains. Compared with patients without sarcopenia, those classified as having sarcopenia had significantly worse scores in physical function (9.1 vs. 32.2), emotional well-being (57.4 vs. 61.1), fatigue (59.9 vs. 44.7), and global health (50.2 vs. 57.5). Additionally, patients with sarcopenia were more likely to experience insomnia (odds ratio [OR] 3.11), fatigue (OR 1.83), and loss of appetite (OR 1.40), further exacerbating symptom burden and reducing overall well-being [16].

Collectively, sarcopenia progression leads to greater physical disability, worsening fatigue, increased nutritional deficits, and a higher prevalence of distressing symptoms. The interplay among muscle loss, malnutrition, and symptom burden further accelerates the decline in functional independence and overall well-being.

Sarcopenia is typically diagnosed using imaging-based methods, body composition analysis, and functional assessment in patients with cancer undergoing surgery or chemotherapy [17]. Computed tomography (CT)-based muscle mass assessment is often used, as routine CT for cancer staging and response evaluation provides an opportunity to assess skeletal muscle depletion, particularly at the L3 level, or in some cases, using the pectoralis muscle index [18-21]. Other methods, such as dual-energy X-ray absorptiometry and BIA, allow whole-body muscle mass estimation [22,23]. In contrast, functional tests, such as the HGS and 6-minute walk test, assess muscle strength and physical performance [24,25].

In terminally ill patients with cancer, sarcopenia assessment is often challenging owing to less frequent routine imaging and a shift in focus from tumor response evaluation to symptom management. Systemic inflammation, cancer-associated cachexia, and prolonged bedridden status further limit the feasibility of advanced imaging and functional testing. Instead, diagnosis in this population requires noninvasive, bedside-friendly approaches prioritizing functional and nutritional status over detailed body composition analysis. The primary goal is not early detection for intervention but symptom monitoring and maintaining QoL.

The SARC-F questionnaire is a widely used screening tool for sarcopenia that evaluates strength, walking ability, ability to rise from a chair, climbing stairs, and history of falls. It is quick, noninvasive, and requires no equipment, making it ideal for palliative care settings [26]. Anthropometric measurements provide simple and accessible estimates of muscle mass and function. HGS, assessed using a dynamometer, serves as a surrogate marker for muscle strength and overall functional capacity and has been associated with frailty, functional decline, and decreased QoL in terminally ill patients with cancer [15,16]. MUAMA, calculated using the mid-upper arm circumference and triceps skinfold thickness, is an indicator of muscle wasting and nutritional status [12,15,16]. Similarly, the CC serves as an estimate of appendicular muscle mass and is correlated with frailty and physical function in older adults receiving palliative care [12,27]. BIA is a noninvasive and rapid method for evaluating skeletal muscle mass and hydration status [28]. Owing to its portability and ease of use, BIA can be performed at the bedside, making it a feasible alternative for sarcopenia assessment in patients who are bedridden or for whom imaging-based evaluations are inappropriate. However, the interpretation may be affected by fluid imbalances and systemic inflammation, which are common in this population [29]. Although each method has limitations, a combined approach may provide the most practical assessment in palliative care.

In terminally ill patients, given their progressive catabolism and limited life expectancy, aggressive interventions provide little benefit and may increase discomfort [30]. Instead, care should prioritize nutritional support, maintenance of mobility, and symptom control tailored to the patient’s prognosis and goals. It is also important to consider that most available evidence does not clearly distinguish among anorexia, cachexia, and sarcopenia, making it essential to interpret management strategies with caution. Although these conditions share overlapping features, their underlying mechanisms and clinical implications differ, necessitating individualized approaches to palliative care.

1. Nutritional support

According to the American Society of Clinical Oncology guidelines, nutritional interventions in palliative care should prioritize maintaining energy intake, minimizing symptom burden, and preserving QoL [31]. According to the European Society for Clinical Nutrition and Metabolism clinical guidelines, indications for nutritional support in patients with advanced cancer should be guided by their estimated life expectancy and clinical situation. For patients with an expected survival time of several months or more, oral nutritional support and parenteral nutrition (PN) may be considered in select cases. For patients with a life expectancy of several weeks, nutritional interventions should be noninvasive, focusing primarily on symptom relief and psychosocial support. For patients with an expected survival of <7 days, total PN is generally avoided because it does not improve outcomes and may cause metabolic distress, potentially increasing discomfort. Instead, care should focus on oral comfort measures, hydration as needed, and minimizing interventions that may compromise QoL [32]. Some nutritional supplements, such as a combination therapy of β-hydroxy-β-methylbutyrate, arginine, and glutamine, have shown potential benefits in increasing lean body mass in patients with cancer [33]. However, most studies have focused on patients receiving disease-directed treatment with limited evidence supporting its use in terminally ill patients [34].

2. Exercise and physical activity

Exercise interventions in palliative care settings have been explored as potential strategies to improve physical function, fatigue, and QoL in patients with advanced cancer. A systematic review and meta-analysis of 14 studies, including 1,034 adults receiving palliative care, found that structured exercise interventions significantly improved exercise capacity, reduced pain and fatigue, and enhanced overall QoL [35]. Similarly, a study assessing the feasibility of a structured two-week exercise program in a palliative care unit found that, despite recruitment challenges, exercise was well tolerated and led to short-term improvements in physical function and QoL [36]. However, various clinical factors, including disease progression, physical function, and patient preferences, may pose hurdles to exercise in palliative care. A systematic review that assessed different exercise interventions, including aerobic, resistance, and combined training reported mixed results in patients with advanced cancer receiving palliative care. While resistance-based exercises improved at least one functional outcome in most studies, overall adherence was highly variable [37]. Despite these limitations, exercise remains a promising intervention that aligns with palliative care goals by enhancing mobility and reducing symptom burden. Feasibility depends on individualized adaptation, patient preferences, and practical considerations such as home-based or remotely supervised regimens. Given the heterogeneity of available studies, further research is needed to establish evidence-based exercise recommendations tailored for terminally ill patients receiving palliative care.

3. Pharmacological interventions

While nutritional support and physical activity remain central to sarcopenia management, pharmacological interventions have been explored to stimulate appetite, reduce inflammation, and mitigate muscle loss in patients with cancer. However, strong evidence supporting their routine use in terminally ill patients or palliative care settings remains scarce. Most studies on appetite stimulants and anti-cachexia therapies have been conducted on patients receiving disease-directed treatment, with limited data on their efficacy and safety in palliative care. Megestrol acetate, a progestin-derived appetite stimulant, has been shown to increase appetite and body weight in patients with cancer; however, its impact on muscle preservation and physical function is unclear [38]. A recent study reported that megestrol acetate showed a potential survival benefit in patients with metastatic gastric cancer who did not receive palliative chemotherapy. However, in multivariate analysis, the impact on survival was not statistically significant in this population. Moreover, the risks of thromboembolism, adrenal insufficiency, and fluid retention limit its use in palliative care, where symptom control and patient comfort are paramount [39]. Some studies have suggested that corticosteroids can temporarily improve appetite and energy levels, offering short-term relief from severe anorexia and fatigue [40]. However, prolonged use accelerates muscle wasting and exacerbates sarcopenia rather than mitigating it [41,42]. Adverse effects, including hyperglycemia, immunosuppression, and osteoporosis, often outweigh the potential benefits [43]. Given these risks, corticosteroids should be cautiously prescribed, prioritizing short-term symptom relief over long-term sarcopenia management.

Inflammation plays a central role in cachexia and sarcopenia, with elevated levels of proinflammatory cytokines contributing to muscle catabolism [44]. Several anti-inflammatory agents have been investigated in patients with cancer, primarily in the context of cancer cachexia rather than in sarcopenia. A systematic review assessed the efficacy and safety of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in patients with cancer cachexia. The review included five randomized controlled trials focusing on indomethacin, ibuprofen, and celecoxib. The findings indicated that there is inadequate evidence to recommend any NSAID for cancer cachexia, whereas celecoxib is generally safe for use [45]. Beyond NSAIDs, other anti-inflammatory agents have been assessed. Thalidomide, an immunomodulatory drug with anti-tumor necrosis factor-α properties, has been investigated in cancer cachexia. A small randomized controlled trial found that improvements in symptoms and cytokine levels did not differ significantly between the thalidomide and placebo groups [46]. A systematic review further highlighted the lack of strong evidence supporting thalidomide for cancer cachexia, with high heterogeneity across studies and poor tolerance in some patients [47]. Similarly, investigational cytokine-targeting therapies have yielded inconsistent results. Although tocilizumab, an interleukin-6 receptor antagonist, has shown potential benefits in reducing inflammatory markers and improving body weight in patients with lung cancer, its effectiveness against cancer cachexia and sarcopenia remains inconclusive and requires further validation [48]. Other investigational anti-inflammatory agents such as infliximab and etanercept have failed to demonstrate efficacy in treating cancer, cachexia, and sarcopenia [49,50]. However, the roles of these anti-inflammatory agents in palliative care settings remain largely unknown. Considering the frailty of this population, the potential harm caused by anti-inflammatory therapies, including immunosuppression, thromboembolic risk, and other toxicities, should be carefully weighed against their uncertain benefits.

Recent advances in cancer cachexia and sarcopenia research have led to the development of novel pharmacological agents. Anamorelin, a selective ghrelin receptor agonist, has been shown in ROMANA 1 and 2 trials to increase appetite, body weight, and lean body mass in patients with advanced cancer [51]. A recent study suggested that ponsegromab, a humanized monoclonal antibody targeting Growth Differentiation Factor 15 (GDF15), was associated with improved weight, appetite, and physical activity in patients with cancer cachexia [52]. Despite promising early results, the role of ghrelin receptor agonist and anti-GDF15 therapy in palliative care has not yet been established. Further studies are required to determine whether these therapies can provide meaningful benefits beyond weight gain in patients receiving palliative care.

Sarcopenia is a prevalent but underexplored condition in terminally ill patients with cancer that contributes to functional decline and reduced QoL. Management should prioritize symptom relief, functional preservation, and patient comfort. Although nutritional and exercise interventions present challenges, they can improve mobility and well-being through individualized approaches. Current pharmacological options are limited; however, ongoing research on emerging therapies may provide future treatment options. A multidisciplinary approach integrating palliative care, nutritional support, and rehabilitation may optimize symptom control and enhance QoL in this vulnerable population. Future research should refine assessment methods and develop patient-centered, noninvasive strategies that align with palliative care principles.

Supplementary materials can be found via https://doi.org/10.14475/jhpc.2025.28.1.10.

No potential conflict of interest relevant to this article was reported.

Study conception and design: SG, HK. Data acquisition: SG, MHK, HK. Data analysis and interpretation: SG, MHK, HK. Manuscript drafting: SG, MHK, HK. Critical manuscript revision: SG, MHK, HK. Final manuscript approval: SG, MHK, HK.