Post‐operative sarcopenia kinetics as an emerging target for improved colorectal cancer outcomes

We read with great interest the recent study by Kesby and colleagues, which introduced the concept of sarcopenia kinetics and demonstrated that the post-operative development of sarcopenia is associated with poorer overall and disease-free survival in patients undergoing colorectal cancer (CRC) surgery 1. The authors are to be commended for their innovative approach and for underscoring the prognostic importance of longitudinal skeletal muscle changes. Their findings raise several important methodological and clinical considerations. Using serial computed tomography (CT) to quantify skeletal muscle index (SMI) offers valuable insight into the evolution of muscle mass after surgery. However, defining sarcopenia by the lowest sex-specific quartile of pre-operative SMI may limit generalizability. Previous studies using international consensus cut-offs have shown that sarcopenia is linked to higher risks of infection and delayed recovery after CRC resection 2. Incorporating functional measures such as grip strength or gait speed could enhance external validity. In addition, the variable timing of post-operative imaging – during which chemotherapy, disease recurrence, or comorbidities may affect muscle mass – introduces potential heterogeneity. Standardizing scan intervals and adopting time-updated analytical models could reduce reverse-causation bias and better capture causal relationships. Because paired CT scans were required, the eligible sample was reduced from 545 to 186 patients, introducing possible selection and immortal-time biases. As seen in other oncological cohorts 3, excluding patients who die early can lead to an overestimation of survival. Comparing baseline characteristics between included and excluded participants, or applying inverse-probability weighting, would help address this limitation. Reporting inter-observer agreement for muscle segmentation would also strengthen measurement reliability. It is noteworthy that new-onset sarcopenia and >10% SMI loss were both associated with worse survival, whereas continuous SMI change showed no linear relationship with outcome. This finding suggests a threshold effect, echoing prior research indicating that marked muscle loss during treatment predicts poor post-operative outcomes 3, 4. Flexible modelling approaches – such as restricted cubic splines – could help identify clinically relevant cut points that trigger nutritional or rehabilitative interventions. As about two-thirds of deaths were cancer-related, competing-risk analyses would further clarify whether sarcopenia kinetics primarily capture cancer progression or general frailty. Looking forward, future work should integrate myosteatosis and functional metrics to provide a more comprehensive picture of physical decline, while incorporating patient-centred outcomes such as quality of life, disability-free survival and days alive and at home. These metrics can help translate prognostic insights into outcomes that matter to patients. Evidence also supports structured prehabilitation – including exercise, nutrition and respiratory training – as an effective way to enhance perioperative resilience and recovery 5. Embedding longitudinal body composition monitoring into CRC survivorship pathways may therefore enable early identification and intervention for patients at risk of post-operative sarcopenia. In summary, Kesby et al. provide compelling evidence that post-operative sarcopenia development and major muscle loss are associated with adverse outcomes after colorectal cancer surgery. Future research that standardizes imaging protocols, mitigates selection bias and includes functional and patient-reported outcomes will help establish sarcopenia kinetics as an actionable target for individualized patient management. Xinyi Xiong: Writing – original draft; writing – review and editing. Qian Cao: Supervision. Guang Yang: Writing – review and editing; supervision. None. None. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This study did not involve human participants, animals, or identifiable personal data. Ethical approval was therefore not required. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.