Sarcopenia in esophageal cancer: from passive prognostic marker to active treatment target

We commend the authors Vongcharoenpol et al. on their publication “Sarcopenia following concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma” (1). Their study provides insight into the prevalence and natural history of sarcopenia in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving chemoradiotherapy (CRT). They report that the prevalence of sarcopenia of 83.6% prior to chemoradiation increased to 91.5% post-CRT in ESCC patients who did not undergo esophagectomy.

The authors’ observation that sarcopenia did not independently predict overall survival or treatment-related toxicity appears to contradict much of the existing literature (2), though admittedly the majority of published studies examine cohorts that have undergone esophagectomy. Multiple studies have demonstrated that post-treatment sarcopenia, rather than baseline sarcopenia, serves as a prognostic marker in esophageal cancer patients undergoing CRT. Ma and colleagues found that post-CRT sarcopenia was an independent predictor of poor overall survival [hazard ratio (HR) =1.697; 95% confidence interval (CI): 1.036–2.780], whilst pre-CRT sarcopenia showed no such association (3). Similarly, Xiao et al. reported that skeletal muscle index loss greater than 12% during neoadjuvant CRT independently predicted mortality (HR =1.76; 95% CI: 1.03–2.99) (4).

The current study’s null findings may reflect several considerations. Firstly, the authors excluded patients who underwent esophagectomy, resulting in a highly selected cohort different to most published series. Their population likely represents patients with more advanced disease, greater comorbidity burden, or treatment response patterns that confound the relationship between sarcopenia and survival. Secondly, the use of Western sarcopenia cutoff values for sarcopenia in a Thai population may have resulted in misclassification, which the authors concede. Asian populations typically have lower skeletal muscle mass than Western populations, and population-specific thresholds are essential for accurate diagnosis of sarcopenia (5).

Perhaps the most clinically relevant finding is the differential rate of skeletal muscle index decline: 3.8% in the sarcopenia group vs. 13% in the non-sarcopenia group. This finding aligns with emerging evidence that the trajectory of muscle loss during treatment may be more prognostically significant than baseline status alone (4,6). Yang et al. demonstrated that continuous sarcopenia throughout radiation therapy conferred the worst overall survival (1,093 days), whilst patients who reduced their sarcopenia status had the best outcomes (2,208 days) (7). This suggests that sarcopenia represents a dynamic, potentially modifiable risk factor rather than a static prognostic marker.

A significant study limitation may be what it reveals about current clinical practice. Despite the high prevalence of sarcopenia in their study group, and what appears to be routine placement of a feeding gastrostomy or jejunostomy tube, there is no mention of a systematic nutritional or exercise intervention in this cohort. This represents a critical gap in care, as robust evidence now supports multimodal interventions to preserve muscle mass and reverse sarcopenia during cancer treatment (8,9).

The National Comprehensive Cancer Network (NCCN) guidelines for esophageal cancer treatment recommend enteral nutrition supplementation when caloric intake falls below 1,500 kcal/day, but this reactive approach may be inadequate (10). Prospective studies have shown that proactive enteral nutrition during CRT can significantly mitigate skeletal muscle loss compared to parenteral nutrition (−1.4 vs. −3.0 cm²/m²) (11). Furthermore, a randomized trial by Xu et al. showed that a nurse-led “walk-and-eat” intervention during neoadjuvant CRT resulted in mitigations in declines in walking distance, hand-grip strength, and body weight loss compared to standard care (12). Exercise interventions appear particularly promising. A recent randomized controlled trial in head and neck cancer patients demonstrated that structured exercise-based rehabilitation during CRT significantly attenuated sarcopenia progression (13). These interventions are feasible during active treatment and may improve not only muscle mass but also treatment tolerance and quality of life.

The high prevalence of sarcopenia before treatment and near-universal prevalence after CRT raises the questions as to whether all patients with locally advanced ESCC should be considered at risk and offered preventive interventions rather than waiting for further muscle loss and providing reactive intervention. A comprehensive approach could include: (I) baseline assessment of muscle mass, strength, and physical function using readily available tools such as computed tomography (CT)-based skeletal muscle index, hand grip strength, and functional tests; (II) early involvement of dietitians to optimize caloric and protein intake; (III) structured and personalized exercise programs incorporating resistance training; and (IV) serial monitoring of body composition throughout treatment to identify patients requiring intensified support (8).

The present study highlights several important research priorities. First, prospective trials are required to determine whether interventions that preserve muscle mass during CRT translate into improved survival, reduced complications and toxicity, and better quality of life in patients treated for esophageal cancer. Second, the optimal composition, timing, and intensity of multimodal interventions involving optimization of nutrition and exercise must be defined in this population.

Vongcharoenpol and colleagues have documented the near-universal prevalence of sarcopenia in patients with locally advanced ESCC receiving CRT. While their findings do not demonstrate an independent prognostic impact of sarcopenia on survival in this non-surgical cohort, the magnitude of muscle loss during treatment and the growing evidence for effective interventions argue strongly for paradigm shift. Sarcopenia should be recognized as a modifiable treatment-related complication requiring proactive management rather than a passive prognostic marker. The integration of nutritional and exercise optimization into standard cancer care represents an evidence-based opportunity to improve outcomes for this vulnerable population.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Gastrointestinal Oncology. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0169/coif). The 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.

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