Sarcopenia in esophageal cancer: causes, clinical implications and future directions—a narrative review

Introduction

Background

Sarcopenia is a progressive muscle disease characterized by a decline in muscle quality and function resulting from adverse structural and metabolic changes that occur throughout the lifespan. The term sarcopenia was first introduced by Rosenberg in the 1980s, initially referring to a loss of body mass (1). Through the years, sarcopenia had different definitions (2). The actual definition was revised in 2018 in light of emerging scientific evidence, highlighting the decline in muscle strength (dynapenia) as the principal determinant of sarcopenia. This updated definition currently represents the most widely accepted framework for identifying and studying the condition. However, the debate about the right definition and diagnosis methodology for sarcopenia is still under debate.

Sarcopenia is a very common condition, affecting 10–17% of elderly people; prevalence across studies changes according to the definition of sarcopenia that is used (2,3). It is currently formally recognized as a muscle disease in the International Classification of Diseases (1).

Prevalence is higher in critically ill and oncologic patients. In a review published in 2022 by Surov and Wienke, the all-cancer prevalence seems to be about 35.5%, being higher in esophageal cancer (51.3–54.4%), prostate cancer, cervical cancers and sarcoma. Among the patients with esophageal cancer, in the same study the prevalence seems to be lower in patients with initial-stage disease: a prevalence of 48.5–51.8% in the curative setting versus 69.5–79% in the palliative setting (4). According to Elliot and colleagues (5), after neoadjuvant therapy sarcopenia can affect the 30.8% of the cases; however, the increase in prevalence does not seem to depend on cT, cN, dysphagia, disease progression and change in performance status.

The prevalence rate is heterogeneous in patients with esophageal cancer and in the different studies ranges from 14.4% to 83% (Table 1).

Rationale and knowledge gap

The prevalence of sarcopenia inevitably increases with age, as both muscle mass and strength progressively decline. Sarcopenia can negatively affect a patient’s ability to recover from surgery due to reduced muscle mass, which impacts nutritional status, immune function, and overall physical resilience.

In recent years, the research on the relationship between sarcopenia before and after the treatment of esophageal cancer, as well as its impact on prognosis and survival, has increased rapidly. Sarcopenia has become a key prognostic factor in esophageal cancer and seems to have an important impact on postoperative complications and overall prognosis. Consequently, assessing sarcopenia should be integrated into the esophageal cancer management clinical practice, enabling clinicians to identify high-risk patients. This could allow for implementing prehabilitation strategies, such as nutritional and physical rehabilitation, that could be useful to optimize treatment outcomes and improve postoperative recovery. In this new review, we attempt to fill the gaps evident even in the most recent reviews (12,13) and focus attention on patients undergoing esophagectomy rather than solely on patients with esophageal cancer. Moreover, we want to discuss the role of artificial intelligence (AI) in the diagnosis and management of sarcopenic patients with esophageal cancer.

Objective

The aim of this review is to evaluate relationships between sarcopenia and post-operative complications or survival outcomes in patients undergoing esophagectomy for esophageal cancer. Furthermore, possible pre-operative strategies to prevent complications and improve conditions of sarcopenic patients were also evaluated. The aim of this review is also to provide an update and summary of the latest articles on sarcopenia in esophageal cancer and to understand the possible future developments and research objectives in this field, also regarding the role of AI. We present this article in accordance with the Narrative Review reporting checklist (available at https://aoe.amegroups.com/article/view/10.21037/aoe-2025-1-30/rc).

Methods

This narrative review is a summary of the publications that we consider relevant found through literature research performed across three electronic databases: PubMed/MEDLINE, Scopus, and Web of Science. The search strategy combined Medical Subject Headings (MeSH) terms and free-text keywords related to sarcopenia and esophageal cancer surgery.

The following search terms were used: “sarcopenia”, “esophageal cancer”, “esophagectomy”, “muscle mass”, “skeletal muscle index”, “nutritional status”, “prognosis”, “postoperative complications”, and “outcomes”.

The search was limited to studies published between January 2000 and February 2025, in order to avoid old data that has been superseded by current literature and include only data reflecting advances in both surgical techniques and body composition assessment methods.

Only articles published in English were considered.

We included original studies, meta-analyses, and systematic reviews that focused on adult patients undergoing esophagectomy for cancer and investigated the relationship between preoperative sarcopenia—assessed through computed tomography (CT)-based muscle mass analysis or clinical criteria—and short- or long-term outcomes after esophagectomy. Eligible study types included retrospective and prospective cohort studies, systematic reviews, and meta-analyses. Case reports, conference abstracts, animal studies, editorials, studies not primarily focused on esophagectomy, and non-English publications were all excluded.

The selection process consisted of three steps:

• Initial screening of titles and abstracts to identify potentially relevant studies;
• Full-text review of selected articles to confirm eligibility;
• Manual search of the reference lists of included papers to identify additional relevant studies.

Due to the narrative nature of this review, no formal quantitative synthesis or risk of bias assessment was conducted. The selection of papers was performed by all authors.

This methodological approach aimed to provide a comprehensive yet qualitative synthesis of the available literature, focusing on the latest advancement in literature, highlighting key findings, clinical implications, and knowledge gaps in the relationship between sarcopenia and esophagectomy outcomes. The search methodology is summarized in Table 2.

Pathophysiology and causes of sarcopenia in esophageal cancer

Malnutrition

Malnutrition is a major and well-established contributor to the development and progression of sarcopenia, particularly in elderly individuals and patients with chronic diseases. Sarcopenia is closely linked to protein-energy malnutrition (PEM), that is characterized by insufficient intake of calories and/or protein to meet metabolic demands. In the setting of inadequate protein intake, muscle protein synthesis is significantly reduced, while muscle protein breakdown often increases, leading to a negative nitrogen balance and a gradual loss of muscle mass.

Moreover, malnutrition is frequently accompanied by micronutrient deficiencies, which are critical for muscle metabolism, mitochondrial function, and neuromuscular health. Malnutrition also compromises hormonal balance, reducing the availability of anabolic hormones like insulin, insulin growth factor-1 (IGF-1), and testosterone, and increasing catabolic stimuli such as cortisol.

In clinical populations, malnutrition may result from a combination of reduced dietary intake, malabsorption, increased metabolic demands, and altered gastrointestinal function. In patients with esophageal cancer, factors such as anorexia, nausea, mucositis, dysphagia, early satiety, and taste alterations contribute to decreased nutrient intake. In this group of patients, the presence of esophageal cancer can also lead to impossibility to admit oral food for the esophageal stenosis created by the tumor. Moreover, esophago-gastric tumors lead also to a decrease in the micronutrients absorption rate. Inadequate nutritional intake over time impairs myogenesis (the formation of new muscle fibers), accelerates mitochondrial dysfunction, and exacerbates oxidative stress, all of which contribute to muscle atrophy.

Importantly, malnutrition not only induces quantitative loss of muscle tissue, but also affects muscle quality, leading to infiltration of fat and fibrotic tissue, a phenomenon known as myosteatosis, which further compromises muscle strength and function. Therefore, malnutrition acts as both a trigger and amplifier of sarcopenia, especially when combined with other factors. Addressing malnutrition is thus a cornerstone in the prevention and management of sarcopenia, requiring comprehensive nutritional assessments, individualized dietary interventions, and—in some cases—supplementation with oral nutritional supplements (ONS) or enteral/parenteral nutrition. Timely recognition and correction of malnutrition are essential to preserve muscle mass, improve physical performance, and enhance clinical outcomes in at-risk populations (14).

Inflammation

Chronic low-grade inflammation is one of the key pathophysiological mechanisms underlying the development of sarcopenia, both in the elderly and in patients with chronic diseases, including esophageal cancer (15).

A key role is played by interleukine-6 (IL-6), that not only promotes protein breakdown but also induces insulin resistance, impairing the anabolic actions of insulin on muscle tissue. Moreover, pro-inflammatory cytokines disrupt the activity of satellite cells, which are essential for muscle regeneration, thereby impairing the muscle repair process and contributing to the progressive decline in muscle mass and strength. An important role is played by the growth hormone-IGF-1 axis and reduces levels of anabolic hormones such as testosterone and IGF-1, amplifying the overall catabolic state (16).

In cancer patients, inflammation is often intensified by the tumor microenvironment, which secretes inflammatory mediators and chronically activates the immune system in a dysfunctional manner. This contributes to a state of inflammatory cachexia, characterized by rapid and severe muscle wasting. In particular, esophageal cancer is related to an intense inflammatory infiltrate that increases the incidence of sarcopenia. Therefore, systemic inflammation acts not merely as a consequence of chronic disease or malignancy, but as an active causal factor in the onset and progression of sarcopenia. It also represents a potential therapeutic target (17).

Elderly

Over the age span from 20 to 80 years of age, there is approximately a 30% reduction in muscle mass and a decline in cross-sectional area of about 20% (18). This is due to a decline in both muscle fiber size and number. Moreover, there is also a shift in muscle fiber composition: a higher type I/type II fiber ratio is observed in the elderly. Type I fibers are used in daily activities and during submaximal exercise while type II are used more during exercise. Type II fibers demonstrate selective atrophy (with a preservation of type I fiber area) with age (19). Sarcopenia is the key component of the development of frailty, a typical condition during elderly.

The biological basis of sarcopenia (20) is over the objective of this paper but, for completeness, are shortly summarized in Table 3.

Neoadjuvant therapy

Neoadjuvant therapy is a risk factor for sarcopenia, with an odds ratio (OR) of 1.51 (21); among patients treated with neoadjuvant therapy, sarcopenia is more common among those with a digestive malignancy (OR: 1.74) if compared with patients with a non-digestive malignancy (OR: 1.37).

Based on this evidence, the onset of sarcopenia during neoadjuvant therapy is an independent risk factor for decreased overall survival (OS) among patients affected by esophago-gastric tumors (8).

The most recent guidelines (22) emphasize the importance and great impact on oncological outcomes of neoadjuvant therapy on esophageal cancer patients compared with upfront surgery, which remains indicated in a select few cases, so more and more patients are being referred for neoadjuvant chemotherapy. Therefore, it is increasingly common to deal with sarcopenic patients before surgery. For this reason, all patients who start neoadjuvant chemotherapy should be followed by a nutritionist. Voisinet and colleagues (23) showed the big impact of a feeding jejunostomy in the prevention of sarcopenia in patients that undergo neoadjuvant chemotherapy for esophageal cancer.

Among the causes of sarcopenia after neoadjuvant therapy nausea, vomiting and raise in muscle mass have to be included. Jin and colleagues (8) found that preoperative sarcopenia is an independent unfavorable predictor for the prognosis of patients with esophageal cancer. After neoadjuvant chemotherapy, the incidence of sarcopenia seems to increase of 15.4%. The impact of neoadjuvant therapy is also in the reduction of patients mobility. Patient undergoing neoadjuvant therapy conducts a less active life and this can lead to further reduction in muscle mass.

Identification of nutritional issues and sarcopenia

As we said before, sarcopenia definition is changed across the years and a debate about sarcopenia definition is still present. We avoid getting involved in this discussion and in the debate about the right method to diagnose sarcopenia because are over the objective of this review.

Considering the frequent coexistence of nutritional issues and their synergic effects on patients scheduled for esophagectomy for cancer, early identification through validated tools is essential for prehabilitation and perioperative care of such patients. Various screening and diagnostic tools are available, each with different characteristics (Table 4).

In this section, we will only shortly discuss about the most used in clinical practice. Because all patients scheduled for esophageal surgery have a CT scan available, is easy to calculate the Psoas Muscle Index (PMI). This index is calculated easily: the PMI is the cross-sectional area of both psoas muscle relative to patient height. Is important because it is a reliable indicator of patients’ nutritional status and is predictive about postoperative complications. The cut-off for PMI is <4.25 sqcm/sqm for males and <3.64 sqcm/sqm for females. This value is related to the prognosis of esophageal cancer (30-33). Male patients with a PMI >5.3 sqcm/sqm had lower postoperative complication (P=0.02) while patients with a lower PMI had a lower OS rate (P<0.001 at univariate analysis and P=0.02 at multivariate analysis).

Perioperative and postoperative impact on outcomes

Increasing evidence suggests that sarcopenia is strongly associated with adverse postoperative outcomes, including increased morbidity, prolonged hospital stays, and a higher risk of complications. It is also considered a predictor of postoperative complications and long-term prognosis in cancer patients (34,35). In Figures 1,2, you can see the variation of PMI in a patient undergone esophagectomy. Figures show the important impact of esophagectomy in the patient and how sarcopenia can be developed during the surgical cares.

Figure 1 Post-operative picture of patient that underwent total esophagectomy for esophageal adenocarcinoma. In the picture a sarcopenic condition can be noted. The image is published with the patient’s consent.

Figure 2 Pre-operative and post-operative evaluation of psoas muscle dimension and area in the same patient, showing important decrease of psoas muscle area. The image is published with the patient’s consent.

However, the impact of preoperative sarcopenia on postoperative outcomes in patients undergoing esophagectomy remains a subject of debate. While some studies have identified preoperative sarcopenia as an independent predictor of postoperative outcomes in esophageal cancer patients (36-39), others have found no significant correlation between preoperative sarcopenia and OS rates in this population (24,40).

The prognosis of esophageal cancer is still poor, with a 5-year survival rate of about 15–34% after surgical resection (25). In esophageal cancer, where surgical resection is a common treatment, the presence of sarcopenia is associated with both diminished quality of life and higher mortality. Park et al. identify increased risk for overall complications, for severe complications (Clavien-Dindo >IIIa) and for pneumonia in sarcopenic patients that underwent esophageal resection, meanwhile, anastomotic leakage rate was similar between sarcopenic and non-sarcopenic patients (26). Jogiat et al. reported that sarcopenic patients with resectable esophageal cancer had reduced OS and disease-free survival (DFS). Moreover, they experienced an increase in postoperative pulmonary complications and anastomotic leakage (31).

The conflicting evidence reported in the literature can be attributed to the variability among systematic reviews and meta-analyses conducted on this topic. There is considerable variation in the markers used to assess sarcopenia via CT imaging, including different threshold values, the selection of segmented muscles, and the choice of CT scan timing (e.g., preoperative, disease staging, or restaging). Similarly, most of these studies have been conducted in Asian countries, where squamous cell carcinoma (SCC) is the predominant histological subtype (27,39).

For this reason, Chen et al. conducted a subgroup analysis revealing that in Asia, preoperative sarcopenia increases the risk of overall complications in patients undergoing esophagectomy. However, in Europe and America, preoperative sarcopenia did not appear to raise the risk of complications after resection, despite its higher prevalence in these populations compared to Asian cohorts. Conversely, preoperative sarcopenia was associated with reduced OS and recurrence-free survival (RFS) in both Asian and European populations. Additionally, it increased the risk of postoperative anastomotic leakage. At the same time, no significant impact was observed on postoperative infections or in-hospital mortality (6).

In patients with unresectable esophageal cancer, neoadjuvant treatment, either chemotherapy or chemoradiotherapy (CRT) is recommended. However, the prognosis remains discouraging with 5 years of survival rates following chemotherapy or CRT of around 30% independently from sarcopenia (28).

Before or during these treatments, it is essential to implement nutritional assessment, as sarcopenia plays a critical role in altering the prognosis of these patients. Deng et al. (25) and Anandavadivelan et al. (29) identify that in patients with unresectable advanced esophageal cancer receiving chemoradiotherapy, sarcopenia was also significantly correlated with worse prognosis and may be associated with higher risk of toxicity during administration of chemotherapy.

Moreover, the incidence of sarcopenia can increase by up to 17% from the start of neoadjuvant chemotherapy to the completion of treatment in individuals with tumors (41).

Preoperative evaluation of sarcopenic patients

The patient who is a candidate for esophagectomy is a complex patient, therefore a careful preoperative risk assessment is essential to optimally evaluate the patient. This perioperative evaluation is based on American Society of Anesthesiologist (ASA) classification, Metabolic Equivalent of Task (MET), which can be considered a surrogate of cardiopulmonary exercise testing (CPET), that indicates the cardio-respiratory-muscular response to maximal exercise by identifying an anaerobiosis threshold, Lee Index (revised cardiac risk index), ARISCAT score (a score for post operatory pulmonary complications), clinical frailty scale (CFS) and a careful anamnesis of comorbidities (42).

Every esophageal cancer patient scheduled for esophagectomy should be thoroughly evaluated for sarcopenia too (26). Sarcopenia examination and severity classification could be a useful tool to optimize the patient before the surgery (43).

According to a recent meta-analysis (44), the diagnosis of sarcopenia before surgery is associated with negative post-operative outcomes such as high mortality, complications (higher risk for atelectasis, pleural effusion, pneumonia, extubation failure, prolonged mechanical ventilation, dysphagia, malnutrition, delay mobilization), and increased hospital stay (26).

Therefore, sarcopenia could be used as an index to identify patients at high risk of postoperative complications and that may require preoperative optimization, together with a less invasive surgical approach or postoperative intensive care admission (45).

The treatment of sarcopenia is mainly based on a multicomponent approach that includes physical activity (a combination of aerobic and resistance exercises), nutritional and pharmacological support before surgery (26,45).

Postoperative sarcopenia and prognosis in esophageal cancer

Postoperative sarcopenia, defined as the loss of skeletal muscle mass and strength after surgery, represents a significant complication in patients underwent esophagectomy for esophageal cancer.

Several causes may lead to the loss of muscle mass and strength after surgery for esophageal neoplasms.

This type of surgery is a demolitive surgical procedure characterized by a change in the anatomical structure of the digestive tract. This can lead to significant metabolic changes, such as impaired nutrient absorption and nutritional deficiencies, as well as alterations in intestinal motility that may contribute to muscle mass loss.

Postoperative sarcopenia can also be associated with malnutrition, which often affects these patients both in the preoperative and postoperative phases, disuse, due to the complexity of the surgical procedure, prolonged hospital stays and the use of devices such as thoracic and abdominal drains that hinder patient mobilization, and hyper catabolism related to the disease itself.

Due to its minimally invasive and less painful nature, thoracoscopic esophagectomy may also facilitate earlier postoperative mobilization, thereby reducing the risk of disuse-induced muscle atrophy.

Furthermore, postoperative sarcopenia is associated with worse clinical outcomes, including a higher incidence of postoperative infections, delayed mobilization, and impaired tissue healing and regeneration (10).

Sarcopenic patients undergoing esophagectomy are at a higher risk of developing postoperative complications compared to non-sarcopenic patients (46). Sarcopenia has been identified as an independent risk factor for the occurrence of anastomotic leaks and pulmonary complications, further underscoring the clinical relevance of preoperative nutritional and functional assessment in this patient population (26).

This increased risk is partly due to the loss of muscle mass and strength, which can lead to reduced thoracic expansion in the postoperative period. This functional impairment predisposes patients to a higher incidence of atelectasis, pleural effusion, and pneumonia.

Moreover, muscle wasting involving the thoracic wall may be associated with difficulty in weaning from mechanical ventilation, often requiring prolonged ventilatory support. This, in turn, increases the risk of ventilator-associated pneumonia (VAP) and other respiratory complications (47).

Treatment of sarcopenia and prevention of sarcopenia-related complications

Several strategies for preventing sarcopenia-related complications in patients with esophageal cancer include:

• Preoperative assessment
  Nutritional screening: evaluate body mass index (BMI), serum albumin, prealbumin levels and caloric intake.
  Muscle mass evaluation: use CT at the L3 vertebral level to assess skeletal muscle mass.
  Functional tests: measure handgrip strength, conduct a 6-minute walking test (6MWT), and perform the chair stand test to evaluate functional capacity.
• Preoperative nutritional optimization
  Implement a high-protein, high-calorie diet to support muscle mass preservation and optimize metabolic function.
  Supplementation with immuno-nutrients: consider supplementation with arginine, glutamine, omega-3 fatty acids, and nucleotides, which have shown potential in improving immune function and reducing postoperative complications (48). In particular, glutamine has been shown to enhance gastrointestinal mucosal function, while omega-3 fatty acids reduce the inflammatory response by decreasing the release of pro-inflammatory factors (49).
  • Early postoperative nutrition Early enteral nutrition, that should be started within 24–48 hours post-surgery, when possible.
    Enteral nutrition is preferred over parenteral nutrition, as the latter may impair brush border enzyme activity, decrease microvilli height, and reduce the function of nutrient transporters in enterocytes. Therefore, enteral nutrition offers several advantages over parenteral nutrition in the perioperative period. Parenteral nutrition should be used only when enteral nutrition is either not feasible or insufficient to meet the patient’s needs (50).
  • Monitoring of caloric and protein requirements The recommended caloric intake is 25–30 kcal/kg/day, with a protein intake of 1.2–2 g/kg/day to support recovery and muscle preservation.
    Supplementation with amino acids, vitamin D, vitamin B12, and iron should be considered if deficiencies are detected (51).
  • Early mobilization and physiotherapy
    Early mobilization (within 24–48 hours) should include activities such as walking, respiratory exercises, and bed exercises. Early mobilization has been demonstrated to reduce the risk of postoperative complications, accelerate recovery in the postoperative period, shorten hospital stays, and positively impact the psychological well-being of patients (52).
• Postoperative exercise programs
  Personalized resistance and strength training should be incorporated into both preoperative and postoperative care plans. Tailored exercises help maintain muscle mass, improve functional capacity, and enhance recovery outcomes in surgical patients (53).
  Structured physical therapy should be implemented to preserve muscle mass. This approach plays a crucial role in maintaining muscle strength and function, particularly in patients at risk of sarcopenia, and contributes to improve postoperative recovery and overall health outcomes (4,54). Pharmacological therapies (in selected cases).
  Also with limited data because this section is over the objectives of the review, pharmacological therapies have to be cited. Anabolic agents (e.g., testosterone, selective androgen receptor modulators (SARMs) or anti-catabolic agents [e.g., angiotensin-converting enzyme (ACE) inhibitors] in patients with severe sarcopenia, under strict medical supervision, may help to improve muscle mass and function in patients with cancer or undergoing major surgery.
• Multidisciplinary follow-up
  A multidisciplinary team approach should be adopted, involving surgeon, nutritionist, physiotherapist, oncologist, and psychologist. Regular monitoring of the patient’s nutritional status, functional capacity, and psychological well-being is essential to optimize outcomes and prevent complications.

Discussion and future perspectives

Sarcopenia is increasingly recognized not only as a negative prognostic factor but also as a potential target for therapeutic and supportive care strategies in esophageal cancer. It is associated with reduced treatment tolerance, increased postoperative complications, and poorer OS and DFS. Despite abundant retrospective evidence linking sarcopenia to adverse surgical and oncologic outcomes, a crucial shift is needed from passive observation to active intervention.

Diagnostic standardization

A major barrier to progress lies in the heterogeneity of diagnostic criteria; thus, standardization of definitions and methodologies represents a critical first step. The variability in defining sarcopenia across studies—particularly between the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) and the Asian Working Group for Sarcopenia (AWGS)—remains problematic. These frameworks differ not only in conceptual emphasis—EWGSOP2 identifies low muscle strength as the primary diagnostic criterion, whereas AWGS prioritizes reduced muscle mass—but also in diagnostic thresholds and assessment tools (43). This heterogeneity limits cross-study comparability and impedes the consolidation of evidence required for clinical implementation.

Furthermore, discrepancies extend to the relative emphasis on muscle mass, strength, and physical performance, as well as to sex- and ethnicity-specific cutoff values (4). Inconsistencies in measurement techniques further compound the issue. Among these, CT-derived skeletal muscle index (SMI), particularly measured at the L3 vertebral level, has emerged as a promising tool for preoperative risk stratification and survival prediction, given the routine use of imaging in esophageal cancer staging (13). However, the absence of standardized anatomical landmarks, threshold values, and image acquisition parameters continues to hinder reproducibility. Consensus building and validation of practical, broadly applicable diagnostic frameworks are therefore essential.

Technological advancements

In parallel, radiomics and AI-based assessments of muscle quality and composition have shown potential to enhance precision risk stratification. Advances in radiomic feature extraction from CT and positron-emission tomography (PET) imaging have enabled characterization of microstructural muscle properties—including intramuscular fat infiltration (myosteatosis) and morphological heterogeneity—that may correlate with patient outcomes more strongly than volumetric indices, reflecting functional impairment and systemic inflammation (55,56). These radiomic parameters have demonstrated strong prognostic value, independent of SMI. Nevertheless, current radiomic models remain insufficiently standardized and poorly integrated with clinical metrics of physical function, such as grip strength or gait speed. Future studies should therefore correlate radiomic phenotypes with validated functional and oncologic outcomes, facilitating their incorporation into composite prognostic models.

The integration of AI into the study of sarcopenia in patients with esophageal cancer has rapidly evolved, driven by the need for accurate quantification of muscle mass loss and its incorporation into prognostic models. As early as the late 2010s, the application of convolutional neural networks (CNNs) and deep learning methods to automated analysis of routine CT images demonstrated promising performance in skeletal muscle segmentation at the L3 vertebral level and in the calculation of the SMI, enabling faster and more reproducible measurements compared with traditional manual analysis (57). In the early 2020s, systematic reviews on the use of AI models for body composition and sarcopenia assessment on CT imaging confirmed that these algorithms achieve high segmentation accuracy (Dice similarity coefficients around 0.94) and highlighted their potential for future clinical integration (58). More recently, studies focusing specifically on esophageal and gastroesophageal cancers have combined CT-based radiomics with machine learning techniques to predict disease progression and survival, demonstrating that multimodal AI-based models integrating quantitative imaging features and sarcopenia-related parameters outperform conventional clinical models in prognostic stratification (59). Finally, recent works published in 2025 have further advanced these approaches by introducing fully automated deep learning architectures for skeletal muscle quantification, enabling large-scale sarcopenia assessment with high segmentation accuracy and improved clinical feasibility (60).

Prehabilitation Emerging evidence also underscores the importance of longitudinal assessment of sarcopenia throughout cancer treatment. Dynamic changes in muscle mass during neoadjuvant therapy are independently associated with prognosis and treatment tolerance (61,62). Incorporating periodic imaging or bioimpedance monitoring could enable real-time treatment adaptation, early initiation of supportive care, and optimization of recovery. To actively counteract sarcopenia, multimodal prehabilitation programs are gaining momentum. These combine resistance-based exercise, individualized nutritional support, and psychological optimization, and have shown significant improvements in perioperative functional capacity, particularly in upper gastrointestinal malignancies (63,64). Resistance training appears superior to aerobic or vibration-based modalities in improving gait speed and muscle strength among sarcopenic populations (53,65). However, adherence, feasibility, and optimal duration of such interventions in esophageal cancer remain insufficiently explored, with few tailored clinical trials available. Future research should clarify the timing, intensity, and feasibility of these interventions, particularly in frail individuals.

Nutritional optimization—both through conventional support and specialized immunonutrition—represents another promising frontier. Preoperative supplementation with glutamine, arginine, omega-3 fatty acids, and nucleotides has shown potential to enhance muscle protein synthesis, support immune function, and reduce inflammation and surgical complications (66). The potential benefits of enteral over parenteral nutrition in preserving gastrointestinal mucosa integrity and improving nutrient absorption should also be emphasized. However, randomized clinical trials are needed to determine the optimal timing, duration, and formulation of nutritional interventions in sarcopenic esophageal cancer patients.

Importantly, sarcopenia not only influences surgical outcomes but also modulates systemic therapy efficacy. Sarcopenic patients often experience reduced chemotherapy tolerance, with higher rates of dose delays, toxicity, and treatment discontinuation (11). Recent studies suggest that sarcopenia may also diminish the effectiveness of immune checkpoint inhibitors such as nivolumab, possibly via immunometabolic dysregulation. This vulnerability appears particularly pronounced in men and in patients with recurrent disease. Elucidating the molecular mechanisms underlying these interactions may yield predictive biomarkers and guide improved immunotherapy selection or sequencing strategies.

Another area warranting greater attention is population-specific adaptation. Geographic and histologic variability (e.g., SCC vs. adenocarcinoma) significantly influence baseline body composition and treatment response (67). Most existing data derive from Asian cohorts (primarily SCC) or Western cohorts with adenocarcinoma, yet substantial interpopulation differences exist in sarcopenia prevalence, baseline nutritional status, and therapeutic response. Cross-regional studies are needed to establish population-specific thresholds and ensure the global applicability of sarcopenia-based interventions.

Finally, biological stratification of sarcopenia may further refine risk prediction beyond traditional indices. Standardization of measurement sites, units (e.g., cm²/m²), and thresholds according to sex, BMI, and ethnicity is essential to enhance comparability. Moreover, biochemical markers such as serum creatinine and albumin have been proposed to distinguish clinically relevant sarcopenia from benign low muscle mass. The creatinine-albumin product (Cr × Alb) has shown promise in prognostic stratification, offering an accessible and cost-effective refinement to current approaches (62). Such methods could improve the clinical applicability of sarcopenia assessment, particularly in resource-limited settings.

Research priorities

Future research should therefore address several core domains, including refinement of diagnostic tools to the integration of sarcopenia management into multidisciplinary oncologic care pathways, with the goal of translating observational data into practical, standardized, and modifiable care strategies.

We have summarized in Table 5 all the relevant clinical characteristics of sarcopenia that we have discussed in this paper.

Conclusions

In conclusion, sarcopenia should no longer be viewed solely as a prognostic biomarker but as a modifiable condition requiring multidisciplinary management.

In this regard, a multidisciplinary preoperative assessment included geriatric evaluation is necessary and sarcopenia should be appropriately diagnosed and treated for improving short-term and long-term outcomes of patients with esophageal cancer.

However, this review has also some limitations: it is a narrative review that focuses on some surgical aspects about sarcopenia and focuses on the surgical patient.

Future research must aim to establish standardized diagnostics criteria, leverage radiomic modelling and dynamic imaging, optimize individualized prehabilitation and nutritional strategies, and account for ethnic and therapeutic diversity in order to shift the paradigm of care for esophageal cancer patients undergoing esophagectomy. Coordinated efforts across clinical research, translational science, and healthcare policy will be vital to bring these innovations to bedside practice.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://aoe.amegroups.com/article/view/10.21037/aoe-2025-1-30/rc

Peer Review File: Available at https://aoe.amegroups.com/article/view/10.21037/aoe-2025-1-30/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aoe.amegroups.com/article/view/10.21037/aoe-2025-1-30/coif). D.N. serves as an unpaid editorial board member of Annals of Esophagus from October 2025 to September 2027. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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