Lei Li1
Jiamin Xu- 1Department of Gastrointestinal Surgery, Shaoxing People's Hospital, The First Hospital of Shaoxing University, Shaoxing, Zhejiang, China
- 2Department of Nursing, Shaoxing People's Hospital, The First Hospital of Shaoxing University, Shaoxing, Zhejiang, China
- 3Department of General Practice, Shaoxing People's Hospital, The First Hospital of Shaoxing University, Shaoxing, Zhejiang, China
- 4School of Medicine, Shaoxing University, Shaoxing, Zhejiang, China
Objective: This article systematically reviewed intervention strategies for cancer-related sarcopenia (CRS), providing evidence for researchers to develop targeted treatments.
Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies between 2015 and 2025, followed by literature screening and content analysis.
Results: A total of 3,566 articles were initially identified, and 18 randomized controlled trials (published between 2016 and 2025; sample sizes ranging from 15 to 232) were ultimately included. CRS interventions were categorized into four types: nutritional, exercise, pharmacological, and multidisciplinary.
Conclusion: A CRS intervention needs an integrated approach that combines nutrition, exercise, pharmacology, and a multidisciplinary team (MDT) to improve patients’ functional outcomes and quality of life. Future research should focus on precision approaches and translational medicine.
1 Introduction
According to the 2022 Global Cancer Statistics, the total number of cancer cases is projected to increase to 35.3 million by 2050, indicating a severe global cancer challenge (1). On 2 February 2024, the International Agency for Research on Cancer (IARC) again highlighted the escalating global cancer burden in its latest report, underscoring the urgent need for worldwide attention (2). CRS is one of the key issues emphasized. It is a syndrome characterized by progressive decline in skeletal muscle mass, strength, and function in cancer patients, caused either by the tumor itself or anticancer treatments (3). Its incidence varies significantly across cancer types, reaching 60–80% in patients with pancreatic, gastric, and lung cancers, while remaining relatively lower (20–30%) in those with breast and prostate cancers (4, 5). Unlike age-related sarcopenia, CRS progresses more rapidly, increasing the risk of postoperative complications, reducing chemotherapy tolerance, significantly impairing quality of life, and shortening survival. Annual medical expenditures for CRS patients were 1.5 to 2 times higher than those for non-CRS patients, primarily due to increased hospitalizations, management of complications, and rehabilitation treatments (6). Therefore, early prevention and intervention for CRS are urgent global public health challenges that need to be addressed.
The factors affecting CRS are numerous. Tumor-related factors include inflammatory cytokines secreted by tumors, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which activate the ubiquitin–proteasome system (UPS), accelerating muscle protein degradation. In addition, the Warburg effect leads to systemic energy depletion and disrupted glucose and lipid metabolism in muscle tissue (7). Treatment-related factors include chemotherapy drugs such as platinum-based agents and paclitaxel, which directly impair mitochondrial function and inhibit muscle regeneration. Radiation therapy induces local inflammatory reactions and oxidative stress, resulting in muscle fibrosis. Prolonged bed rest after surgery further accelerates muscle atrophy (8, 9). Patient-related factors include the hypermetabolic state caused by tumors, which leads to insufficient protein intake, particularly a deficiency in branched-chain amino acids (BCAAs). Pain, fatigue, and psychological depression further reduce physical activity. In addition, insulin resistance and dysregulation of the growth hormone (GH)/insulin-like growth factor I (IGF-1) axis suppress muscle synthesis (10). Given these influencing factors, implementing targeted intervention measures to prevent and treat CRS is a question worthy of in-depth research.
At present, insufficient attention is paid to sarcopenia in the treatment of cancer patients. Therefore, we believe that actively implementing interventions for CRS in clinical practice is closely associated with improved treatment outcomes, enhanced patient prognosis, better overall quality of life, and higher healthcare quality.
To address this critical issue, this article adopts a literature review approach to explore interventions for CRS from multiple dimensions, including nutrition, exercise, medication, and multidisciplinary management, with the aim of providing a reference for clinical practice and research.
2 Methods
We conducted a scoping review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Scoping Review extension (PRISMA-SCR) checklist.
2.1 Search strategy
Research question: What are the intervention strategies for CRS?
To address the aforementioned research question, a systematic literature search was conducted in February 2025. A combination of Medical Subject Headings (MeSH) and free-text terms was used to systematically retrieve articles from PubMed, Embase, Web of Science, and the Cochrane Library (accessed via the Ovid research platform). The MeSH terms included “Neoplasms,” “Sarcopenia,” and “randomized controlled trial,” and the search was limited to publications from 2015 to 2025.
2.2 Inclusion and exclusion criteria for literature
2.2.1 Inclusion criteria
Studies were considered eligible if they met the following criteria: (1) participants were aged≥18 years; (2) patients had a pathological diagnosis of cancer; and (3) studies were published in English.
2.2.2 Exclusion criteria
Studies were excluded if they met any of the following conditions: (1) the literature data were incomplete; (2) the literature quality was poor; or (3) the literature type consisted of preliminary experiments or similar reports.
2.3 Literature screening
The retrieved literature was imported into EndNote, and the titles and abstracts were preliminarily reviewed to exclude studies clearly irrelevant to this research. Two researchers independently evaluated the full texts of the remaining articles and cross-checked their selections. If discrepancies arose, they were resolved through discussion or, if necessary, adjudicated by a third researcher, resulting in the final set of included studies.
2.4 Data extraction
Data extraction was performed independently by two researchers. The extracted information included author details, year of publication, country, sample volume, type of study, intervention measures, and results. The extracted data were then compiled and cross-verified by the researchers.
2.5 Quality assessment of the literature
The included randomized controlled trials (RCTs) were evaluated for quality using Version 2 of the Cochrane Risk of Bias tool for randomized trials (RoB2) (11).
3 Results
3.1 Results of literature search
Through systematic retrieval, we obtained a total of 3,566 articles, including 340 from PubMed, 471 from Embase, 823 from Web of Science, and 1,932 from the Cochrane Library. After stepwise screening, 18 articles were ultimately included for analysis. The detailed literature screening flowchart is presented in Figure 1.
Figure 1. PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for research questions between 2015 and 2025. The included studies were identified through literature screening. A total of 18 studies were included, all of which were randomized controlled trials.
3.2 Basic characteristics of the included literature
Eighteen studies published between 2016 and 2025 were included, with sample sizes ranging from 15 to 232 participants. The majority of the studies were conducted in the USA (n = 7, 38.9%), with the remaining studies from the UK (n = 3, 16.7%) and South Korea (n = 2, 16.7%), and one study each from Spain, China, Lithuania, the Netherlands, Italy, Saudi Arabia, and Egypt. The basic characteristics of the included studies are presented in Table 1. A summary table comparing intervention efficacy across categories is presented in Table 2, and the results of the risk of bias assessment table for randomized controlled trials are presented in Table 3.
Table 1. Basic characteristics of the included literature.
Table 2. Efficacy comparison of CRS intervention categories.
Table 3. Risk of bias in studies.
3.3 Intervention strategies for cancer-related sarcopenia
In this review, we summarized interventions for CRS, including nutritional, exercise, pharmacological, and multidisciplinary approaches. The literature classification diagram is shown in Figure 2. In clinical studies of CRS, heterogeneity was prevalent, with core manifestations including differences in intervention effects and low comparability of data. This primarily stemmed from differences in the implementation of intervention methods, differences in the pathological characteristics of tumor types, and differences in the selection of outcome measurement indicators and tools.
Figure 2. The results were analyzed by a content analysis. The interventions for CRS comprised four major categories: nutritional interventions, exercise interventions, pharmacological interventions, and multidisciplinary interventions.
3.3.1 Nutritional intervention
This review included seven studies examining nutritional interventions for CRS. Herrera-Martínez et al. (12) reported that nutritional support with hypercaloric, hyperproteic OS (including whey protein), and vitamin D supplementation was associated with the maintenance of body composition. Additionally, dietary advice in combination with oral nutritional supplements (ONS) was linked to a significantly lower sarcopenia prevalence (13). The randomized controlled trial by Tumas et al. (14) provided evidence that nutritional intervention, specifically immunonutrition, was associated with a lower rate of sarcopenia in the intervention group than in the control group. In contrast, Van der Werf et al. (15) reported that individualized nutritional counseling (NC) by a dietitian for patients undergoing chemotherapy for metastatic colorectal cancer had no effect on muscle mass. Ritch et al. (16) reported that, with enriched oral nutrition supplements (ONS), the proportion of patients with sarcopenia did not change in the ONS group but increased by 20% in the control group (p = 0.01). Another randomized controlled trial demonstrated that whey protein supplementation significantly reduced the incidence of sarcopenia (17). Lee et al. (18) reported that the case group participants consumed protein supplements containing 18 g of protein daily, which led to improvements in sarcopenia.
3.3.2 Exercise intervention
Among the studies included in this review, two reported that aerobic and resistance exercise were positively correlated with skeletal muscle index, effectively attenuating sarcopenia (19, 20). One study reported that home-based resistance training could improve sarcopenia in advanced cancer (21). Moug et al. (22) reported that a 13–17 week telephone-guided graduated walking program, prehabilitation, improved muscle mass in patients with rectal cancer. Dawson et al. (23) reported that a 12-week resistance training intervention effectively improved sarcopenia. The randomized controlled trial by Adams et al. (24) provided evidence that resistance exercise training consistently demonstrated superior effects to usual care for improving sarcopenia-related outcomes. Park et al. (25) reported that a resistance and aerobic exercise program significantly reduced the incidence of sarcopenia. Elnaggar et al. (26) indicated that adaptive-VRT is a promising intervention for ameliorating chemotherapy-induced sarcopenia in pediatric acute lymphoblastic leukemia survivors.
3.3.3 Pharmacological intervention
One study reported that receiving weekly injections of either 100 mg of testosterone enanthate or adjunct testosterone improved lean body mass compared with the placebo group (27).
3.3.4 Multidisciplinary intervention
Pring et al. (28) reported that neuromuscular electrical stimulation (NMES) combined with standard care helped to preserve muscle mass through early postoperative intervention, with NMES allowing a more rapid return to baseline. Another study reported that resistance training and protein supplementation effectively improved sarcopenia (29).
4 Discussion
As a multifactorial-driven complex syndrome, CRS requires intervention strategies that address muscle metabolic imbalance, the inflammatory microenvironment, and the superimposed effects of cancer therapy. In recent years, although some progress has been made in CRS intervention research, numerous challenges remain in clinical translation and individualized application.
Nutritional support and exercise training were regarded as the cornerstone interventions for CRS, yet the limitations of their isolated application were becoming increasingly evident. While high-protein diets could promote muscle protein synthesis, advanced cancer patients often exhibit reduced protein utilization due to metabolic disturbances (e.g., insulin resistance and elevated inflammatory cytokines). In such cases, combined resistance training enhances skeletal muscle sensitivity to amino acids by activating the mTOR pathway, thereby amplifying protein synthesis efficiency and creating a metabolic “synergistic effect.” For instance, a randomized controlled trial in prostate cancer patients demonstrated that resistance training combined with protein supplementation significantly improved sarcopenia (29). However, cancer patients frequently struggle to meet target nutritional intake due to anorexia, gastrointestinal dysfunction, or treatment-related side effects (e.g., chemotherapy-induced nausea). In such cases, personalized adjustments—such as enteral nutrition or ONS—are often required. Notably, while nutritional support alone may delay muscle loss, its impact on muscle strength and physical function remains limited; thus, dual optimization of “quality and quantity” necessitates integration with exercise interventions. Moreover, the modality and intensity of exercise must be dynamically tailored to patients’ functional status. For example, late-stage or severely debilitated patients may benefit from low-intensity progressive training (e.g., breathing exercises and anti-gravity movements). Early-stage patients could achieve superior outcomes with high-intensity interval training (HIIT) (30).
Pharmacological interventions for CRS remain exploratory, with several targeted approaches showing promise but facing clinical challenges. Androgen receptor modulators (e.g., enobosarm) and myostatin antibodies (e.g., bimagrumab) have demonstrated potential in reversing muscle atrophy by selectively targeting anabolic and catabolic pathways (31). However, the clinical application of anabolic agents (e.g., GH/IGF-1 axis modulators) is significantly constrained by their potential tumor-promoting effects, necessitating rigorous benefit–risk assessment—particularly in hormone-sensitive malignancies (e.g., breast and prostate cancers) (32). Anti-inflammatory agents mitigate muscle wasting by suppressing systemic inflammation, yet their long-term use is limited by gastrointestinal and cardiovascular toxicity. Consequently, future research must prioritize precision patient stratification and the development of tissue-selective targeted therapies.
The complexity of CRS necessitates transcending traditional unimodal interventions by establishing multidisciplinary team (MDT) models integrating oncology, nutrition, rehabilitation, and psychological care. For instance, the successful implementation of prehabilitation in colorectal cancer demonstrated that a 13–17 week preoperative rehabilitation program significantly improved muscle mass in patients with rectal cancer (22). During chemoradiotherapy, concurrent nutritional assessment and prehabilitation training effectively prevented muscle loss and enhanced treatment tolerance (33, 34). Psychological interventions demonstrated significant value in improving cancer-related fatigue (CRF) and treatment adherence, although they were frequently overlooked in clinical practice (35). Notably, implementing the MDT model required overcoming practical challenges such as unequal medical resource allocation and inefficient interdisciplinary communication, which was particularly pronounced in primary care institutions, thereby necessitating optimization through standardized protocols and telemedicine technologies.
The management of CRS relies on multidimensional interventions, including nutrition, exercise, and pharmacology. However, single or short-term interventions fail to address patients’ full-course needs, and long-term follow-up is key for improving prognosis. Meanwhile, clinical implementation also faces multiple practical barriers, such as inadequate MDT mechanisms, patient compliance issues and individual differences, a lack of unified long-term assessment standards and tools, and insufficient allocation of medical resources coupled with inadequate primary care capabilities.
5 Conclusion
The management of CRS should follow a “primary prevention-multidimensional intervention-long-term management” framework, integrating nutrition, exercise, pharmacotherapy, and MDT models to optimize functional outcomes and quality of life. Future research must overcome precision and translational medicine barriers while addressing cost-effectiveness and accessibility to benefit the broader patient population.
Author contributions
LL: Writing – original draft, Writing – review & editing. HZ: Writing – review & editing. JC: Writing – review & editing. LS: Methodology, Writing – review & editing. JX: Writing – original draft.
Funding
The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the Medical Science and Technology Project of Zhejiang Province (No. 2024KY467).
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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The author(s) declared that Generative AI was not used in the creation of this manuscript.
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Keywords: cancer, sarcopenia, intervention strategies, rehabilitation, randomized controlled trial (RCT)
Citation: Li L, Zhu H, Chen J, Shan L and Xu J (2025) Intervention strategies for cancer-related sarcopenia: a scoping review. Front. Nutr. 12:1666547. doi: 10.3389/fnut.2025.1666547
Edited by:
Hui-Xin Liu, China Medical University, ChinaReviewed by:
Giuseppe Ferdinando Colloca, Agostino Gemelli University Polyclinic (IRCCS), ItalyShufeng Sun, National Institutes of Health (NIH), United States
Thinakaran Kandayah, Pejabat Kesihatan Daerah Hilir Perak, Malaysia
Copyright © 2025 Li, Zhu, Chen, Shan and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jiamin Xu, Xu eGptOTk2OTk2QDE2My5jb20=