In this retrospective cohort study, the authors investigated a novel approach of assessing for the impact of sarcopenia, over multiple time points, on the outcomes of patients undergoing trimodal therapy for esophageal cancer.1 Sarcopenia, or the physiologic state of reduced skeletal muscle and function, has been frequently reported to be associated with both overall survival (OS) and disease-free survival (DFS) in various surgical oncology cohorts.2 However, there are conflicting reports about the relationship of sarcopenia to the outcomes of patients with esophageal cancer, which the authors address in their investigation.3 Although the authors provide multiple possible explanations for the heterogeneity in results seen among sarcopenic analyses in esophageal cancer patients, they are the first to address one pivotal aspect: timing of CT imaging.

The authors reviewed 141 patients between 2011 and 2018, and of those 118 had CT scans at all time points and thus were included in the final analysis. Consistent with other studies within the Western hemisphere, adenocarcinoma was the predominant histology, representing 85.8% of cases. The method of surgical technique was comparable, with 40.4% undergoing transhiatal esophagectomy and 58.2% undergoing transthoracic esophagectomy.

Sarcopenia analysis was performed at three separate, clinically relevant, time points, including staging, post-neoadjuvant, and 1-year follow-up. Sarcopenia was assessed by measuring skeletal muscle index (SMI) at the frequently reported third lumbar vertebra level. The rates of sarcopenia in the study were relatively low with 15.6% at the initial CT scan; however, this increased to 38% at the post-neoadjuvant CT scan. The reason for the low rate of sarcopenia at the initial assessment is likely because the authors utilized their own method, optimal stratification, to define presence of sarcopenia. This method of determining cut-off values with the greatest statistical significance would produce groupings of the most severe sarcopenia, which the authors acknowledge. This methodology is contrary to other investigations that have adopted frequently cited definitions of sarcopenia, including Martin et al. or Prado et al.4,5 The issue with these commonly used definitions of sarcopenia is that they include both surgical and nonsurgical oncology patients with various malignancies and thus may not generalize to esophageal cancer. The authors’ method of defining sarcopenia in this new way should be encouraged.

The primary outcome was overall survival with mortality occurring in a majority of patients, 66%, with a median duration of 34.5 months. This rate of survival is comparable to prior reports and demonstrates the unfortunately poor outcomes of patients with esophageal cancer, even among those without sarcopenia. They demonstrated that although baseline sarcopenia was not prognostic of OS or DFS, the presence of it at staging and the change in SMI across the three measurement periods was prognostic for both OS and DFS. The authors eloquently hypothesize that the inability to gain muscle after neoadjuvant therapy may be indicative of a cachectic state or physiologic process such as cancer recurrence. Although this hypothesis has not been strongly supported in the literature, this finding encourages future research to identify and mitigate the pathophysiology of this finding.

The authors accounted for the different definitions of sarcopenia by applying Prado et al. cut-offs to their cohort and relating this to outcomes. The authors state that even at the cut-off values defined by Prado et al., sarcopenia was found to be less significantly associated with survival, which is interesting. The authors’ definition of sarcopenia, in contrast, was capturing a more severe group of sarcopenic patients, as mentioned above, likely explaining this difference. However, this is one of the first reports to include multiple definitions of sarcopenia, including a novel definition comprising solely esophageal cancer surgical patients, compared with a traditional definition comprising a heterogeneous group of oncology patients. It would be beneficial for investigations of sarcopenia to include multiple definitions in their analyses as this would enable more robust systematic analysis in the future.

There are limited reports in esophageal cancer, and to some extent surgical oncology cohorts in general, that assess sarcopenia across multiple time points and relate these measurements to outcomes. The authors comment on a study by Jarvinen et al. that investigated differences between pre-neoadjuvant and preoperative sarcopenia in patients with esophageal cancer. The report demonstrated that although pre-neoadjuvant sarcopenia was not associated with OS, the group with a change in SMI below the median correlated with OS (p = 0.022). This finding of change in SMI and poor survival has been reported previously in other oncology cohorts. For example, Nozawa et al. reported that colorectal cancer patients who had a negative change in SMI after neoadjuvant therapy had worse prognosis.6 As the authors indicate, this may be a more important finding than sarcopenia diagnosed at any one time point. Thus, future studies of sarcopenia should be encouraged to assess body composition at multiple time points, if able, and in the appropriate clinical context.

Finally, it is unclear what standard there should be for obtaining CT imaging at three time points within the first year of care provided to patients undergoing surgical resection of esophageal cancer. For example, although the authors reviewed 141 patients, only 118 had CT imaging at each time point. This may make replication of this study difficult, but many patients within the Western hemisphere are likely to obtain imaging this frequently during their care, albeit 75% of the time. Given the differences in outcomes seen at these clinically important time points, assessment for sarcopenia at multiple times points should be encouraged and may encourage more frequent analysis in prospective studies. Although with manual body composition assessment techniques this may increase time to study completion, automated methods, such as those used by the authors, offer a nice alternative to quickly obtain these measurements.