Prognostic impact of low absolute skeletal muscle mass 6 months after gastrectomy for gastric cancer: a retrospective cohort study

Introduction

Gastric cancer continues to be a major global health burden and one of the leading causes of cancer-related mortality worldwide (1). Identifying prognostic factors that predict long-term outcomes after curative resection is crucial for improving patient management. Sarcopenia, characterized by reductions in skeletal muscle mass (SMM), strength, and physical function, has been associated with postoperative complications and poor survival across various cancers, including gastric cancer (2,3).

Preoperative low SMM has been widely recognized as a significant prognostic factor for poor outcomes in gastric cancer patients (4). A recent systematic review demonstrated that preoperative sarcopenia is associated with higher postoperative morbidity and significantly worse overall survival (OS) after gastrectomy, emphasizing the prognostic relevance of body composition in gastric cancer. Previous studies have primarily focused on postoperative skeletal muscle dynamics by assessing relative muscle loss, expressed in this study as ΔPMI (i.e., percentage decrease in SMM) at various time points (5,6). However, these studies have predominantly evaluated ΔPMI, with the prognostic value of absolute SMM at specific postoperative stages remaining unclear.

This study, therefore, aimed to evaluate absolute SMM 6 months after gastrectomy and investigate its prognostic significance for OS and disease-free survival (DFS). We present this article in accordance with the STROBE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-1-976/rc).

Methods

Study population

This retrospective study included 151 consecutive patients who underwent curative gastrectomy for gastric cancer at Nihon University Itabashi Hospital (Tokyo, Japan) between January 2015 and December 2021. The inclusion criteria were as follows: (I) histologically confirmed gastric adenocarcinoma; (II) curative (R0) gastrectomy with lymph node dissection; and (III) availability of both preoperative and 6-month postoperative abdominal computed tomography (CT) scans. Patients were excluded if they had: (I) R1 or R2 resection; (II) positive peritoneal cytology [CY(+)]; (III) missing essential clinical information; (IV) concurrent active malignancies; or (V) recurrence or death within 6 months after surgery. As this was a retrospective cohort study including all eligible patients within the study period, no formal sample size calculation was performed. The study was approved by the Institutional Review Board of the Nihon University Itabashi Hospital (No. RK-211012-6). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The requirement for written informed consent was waived by the Institutional Review Board, and an opt-out method was used to obtain participants’ consent.

Assessment of SMM

SMM was quantified using axial CT images at the level of the third lumbar vertebra (L3). The bilateral psoas muscles were manually traced to obtain their cross-sectional areas, and the sum of these areas was normalized by height squared to calculate the psoas muscle index (PMI, cm²/m²; Figure 1). Sex-specific cutoff values for low absolute SMM were defined as 6.36 cm²/m² for men and 3.92 cm²/m² for women (7). Based on PMI at 6 months postoperatively, patients were assigned to either the low absolute SMM group (L group) or the non-low absolute SMM group (N group). The 6-month time point was chosen because abdominal CT is commonly performed during this period in routine follow-up for many patients, and because it reflects a mid-term recovery phase in which nutritional status and physical function typically stabilize after gastrectomy.

Figure 1 Cross-sectional CT image at the level of the third lumbar vertebra. The borders of the bilateral psoas muscles are manually traced to calculate the cross-sectional area. The PMI is obtained by dividing the total area by height squared. CT, computed tomography; PMI, psoas muscle index.

Definition of ΔPMI

ΔPMI was expressed as the percentage change in PMI and calculated as follows:

ΔPMI=PMIat6months−PreoperativePMIPreoperativePMI×100%[1]

A cutoff value of 10.35% for ΔPMI was determined using receiver operating characteristic (ROC) curve analysis. Patients were therefore categorized into two groups: the Mild-loss group (<10.35% decrease) and the Severe-loss group (≥10.35% decrease).

Data collection

Clinical and pathological data were retrospectively extracted from medical records. Collected variables included demographic characteristics [age, sex, preoperative body mass index (BMI), American Society of Anesthesiologists Physical Status (ASA-PS) score, and diabetes mellitus], nutritional indices [serum albumin level and prognostic nutritional index (PNI)] (8,9), surgical information (type of gastrectomy, extent of lymph node dissection, postoperative hospital stay, and postoperative complications), and pathological features [tumor depth, lymph node involvement, and the Union for International Cancer Control, eight edition (UICC) pathological stage] (10) as well as histological type. Postoperative complications occurring within 30 days were graded according to the Clavien-Dindo classification (11,12), with severe complications defined as grade IIIa or higher.

Skeletal muscle parameters included preoperative PMI, 6-month PMI, and ΔPMI. For patients with stage II/III disease, the initiation and completion of adjuvant chemotherapy were also recorded. Adjuvant chemotherapy was administered to those with pathological stage II/III disease, excluding patients with pT3N0 or pT1 tumors (13).

Statistical analysis

Categorical variables were compared using the χ² test or Fisher’s exact test, as appropriate. Continuous variables were analyzed using the Mann-Whitney U test. OS and DFS were estimated using the Kaplan-Meier method, and differences between groups defined by absolute SMM (L vs. N) and ΔPMI categories were evaluated using the log-rank test. Prognostic factors for OS were examined using Cox proportional hazards regression analysis. Variables with P<0.05 in univariate analyses were entered into multivariate models. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. All statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University), a graphical user interface for R (version 4.0.2) (14). A two-sided P value <0.05 was considered statistically significant.

Results

Patient characteristics

Among the 151 eligible patients (104 men and 47 women), 50 underwent total gastrectomy and 101 underwent distal gastrectomy. According to the UICC pathological classification, 66 patients had stage I disease, 40 had stage II, and 45 had stage III. At 6 months postoperatively, 115 patients (76%) were categorized into the L group and 36 patients (24%) into the N group based on absolute SMM. When classified by ΔPMI, 81 patients (53.6%) were assigned to the mild-loss group (<10.35% decrease) and 70 patients (46.4%) to the severe-loss group (≥10.35% decrease).

Compared with the N group, the L group contained a significantly higher proportion of men, exhibited lower preoperative PMI values, and had more advanced UICC pathological stages (all P<0.05). There were no significant differences between the groups in age, preoperative BMI, ASA-PS score, diabetes mellitus, serum albumin, PNI, extent of gastrectomy, postoperative complications (Clavien-Dindo grade ≥ IIIa), tumor differentiation, ΔPMI, or adjuvant chemotherapy status. Postoperative hospital stay did not differ significantly between the groups (median: 13.5 days in the N group vs. 15.0 days in the L group, P=0.28) (Table 1).

Survival analysis

OS differed significantly between the absolute SMM groups. The L group demonstrated significantly shorter OS than the N group (P=0.006, log-rank test; Figure 2A). However, no significant difference in DFS was observed between the groups (P=0.43, log-rank test; Figure 2B).

Figure 2 Kaplan-Meier survival curves according to absolute SMM at 6 months. (A) Overall survival in the L group vs. N group. (B) Disease-free survival in the L group vs. N group. L group, low absolute SMM; N group, non-low absolute SMM. SMM, skeletal muscle mass.

When patients were stratified by ΔPMI, neither OS (P=0.11, log-rank test; Figure 3A) nor DFS (P=0.34, log-rank test; Figure 3B) differed significantly between the mild-loss and severe-loss groups.

Figure 3 Kaplan-Meier survival curves according to ΔPMI. (A) Overall survival according to ΔPMI category. (B) Disease-free survival according to ΔPMI category. Mild-loss group, <10.35% decrease; severe-loss group, ≥10.35% decrease. ΔPMI, relative muscle loss.

To address potential imbalance in pathological stage between the L and N groups, additional stage-stratified survival analyses were performed. Within both the stage I and stage II–III subgroups, patients in the L group consistently showed poorer OS than those in the N group, although the differences were not statistically significant (stage I: P=0.13, log-rank test; stage II–III: P=0.051, log-rank test) (Figure 4).

Figure 4 Kaplan-Meier overall survival curves according to absolute SMM category, stratified by pathological stage. (A) Stage I. (B) Stage II–III. L group, low absolute SMM; N group, non-low absolute SMM. SMM, skeletal muscle mass.

During follow-up, 35 patients died (N group, n=2; L group, n=33). In the N group, both deaths were due to gastric cancer progression. In the L group, causes of death included gastric cancer progression (n=20), other malignancies (n=5), pneumonia (n=4), heart failure (n=1), and senility (n=3).

We further evaluated survival according to preoperative SMM. Kaplan-Meier survival curves comparing patients with low versus normal preoperative SMM showed no significant differences in OS (P=0.70, log-rank test; Figure 5).

Figure 5 Kaplan-Meier overall survival curves according to preoperative skeletal muscle mass category (L group vs. N group). L group, low absolute SMM; N group, non-low absolute SMM. SMM, skeletal muscle mass.

Multivariate analysis

Multivariate Cox proportional hazards analysis identified two independent prognostic factors for OS: low absolute SMM at 6 months (L group vs. N group; HR =4.660, 95% CI, 1.111–19.550; P=0.03) and UICC pathological stage (stage II/III vs. I; HR =4.711, 95% CI, 1.749–12.690; P=0.002, Table 3). ΔPMI was not significantly associated with OS or DFS in either univariate or multivariate analyses.

Subgroup analysis: adjuvant chemotherapy

Among patients with stage II/III disease, the initiation rate of adjuvant chemotherapy was 60.9% in the L group and 56.2% in the N group (P=0.78). Completion rates were 47.6% and 55.6%, respectively (P=0.73; Table 2). Thus, low absolute SMM at 6 months did not significantly influence the initiation or completion of adjuvant chemotherapy.

Recurrence patterns and post-recurrence treatment

A total of 26 patients experienced recurrence (N group: 5; L group: 21). The distribution of recurrence sites was as follows: peritoneal dissemination (n=15), liver (n=6), lung (n=5), lymph nodes (n=3), local recurrence (n=2), bone (n=1), and tumor marker elevation alone (n=1). When multiple sites of recurrence were identified at the time of initial relapse, each site was counted independently. Regarding post-recurrence treatment, 17 patients received systemic chemotherapy, 2 patients underwent surgery, and 7 patients received best supportive care (BSC). BSC was more frequently observed in the L group (n=6) than in the N group (n=1).

Discussion

This study examined the prognostic significance of absolute SMM at 6 months after curative gastrectomy. The primary finding was that low absolute SMM, defined using sex-specific PMI cutoffs, independently predicted poor OS, whereas ΔPMI showed no association with prognosis. Additionally, low absolute SMM did not affect the initiation or completion of adjuvant chemotherapy, suggesting that its prognostic impact is more closely related to long-term host resilience than to short-term treatment tolerability.

A major strength of this study is the use of a clearly defined mid-term postoperative time point. Six months after gastrectomy represents a physiologically stable phase in which nutritional status and physical function generally recover and plateau. Prior studies have reported that SMM decreases rapidly during the first postoperative month but stabilizes and partially recovers within 3 to 6 months (15). Thus, the 6-month assessment is well positioned to reflect true postoperative physiological reserve. Another advantage is the use of routine follow-up CT imaging to quantify absolute SMM. This method is objective, widely accessible, and easily integrated into clinical practice.

Previous studies have demonstrated that preoperative sarcopenia is associated with increased postoperative morbidity and poor survival in gastric cancer (2-4). In addition, early postoperative declines in body weight or muscle mass have been linked to poor tolerance of adjuvant chemotherapy (16). Several reports have further suggested that relative postoperative muscle loss—whether during the early postoperative period or up to 1 year after surgery—is associated with long-term survival (5,6). These studies largely focus on “how much muscle was lost” relative to the preoperative baseline. In contrast to these investigations focusing on relative changes, the present study highlights the importance of the absolute muscle reserve. ΔPMI, representing relative postoperative muscle loss, is influenced by preoperative baseline values; patients with higher preoperative PMI may experience substantial relative loss but still retain adequate muscle reserves, whereas patients with low baseline PMI may reach critically low muscle levels with only modest decline. This may partly explain why ΔPMI was not associated with survival in this study, while absolute SMM at 6 months was a significant predictor. Furthermore, stage-stratified analyses demonstrated that the association between low absolute SMM at 6 months and poorer OS was consistently observed within each pathological stage, suggesting that this relationship is not solely attributable to differences in tumor stage. In the present study, postoperative hospital stay did not differ significantly between the L and N groups. This finding suggests that reduced SMM at 6 months may not be explained solely by delayed postoperative recovery or prolonged hospitalization, and may instead reflect more complex physiological changes during the postoperative course.

Several mechanisms may explain why low absolute SMM at 6 months is associated with poor survival. Diminished muscle mass reflects reduced physiological reserve and systemic frailty. Factors such as persistent malnutrition, chronic inflammation, and reduced physical activity may contribute to sustained muscle depletion and, consequently, greater vulnerability to non-cancer-related complications, including infections or organ dysfunction (17). In the present study, non-cancer-related deaths were more commonly observed in the L group—including other malignancies, pneumonia, heart failure, and senility—which may reflect the systemic vulnerability associated with low muscle reserve. Among patients who developed recurrence, BSC was administered to 6 patients in the L group and 1 patient in the N group. This pattern suggests that patients with low muscle mass at 6 months may experience functional or physiological decline at recurrence, limiting their eligibility for systemic treatments. Reduced feasibility of post-recurrence therapy may have contributed to the poorer OS observed in the L group, even in the absence of a difference in DFS. These findings suggest that mid-term postoperative muscle depletion likely reflects underlying frailty affecting both non-cancer-related mortality and the ability to receive effective treatment after recurrence.

From a clinical perspective, routine evaluation of absolute SMM at 6 months using CT imaging may offer a simple, reproducible tool for postoperative risk stratification. Patients identified as having low muscle mass at this stage may benefit from personalized nutritional interventions, structured resistance exercise programs, and more intensive follow-up. Prospective interventional trials are needed to determine whether improving mid-term postoperative SMM can lead to improved survival outcomes.

This study has several limitations. First, its retrospective single-center design and limited sample size may restrict the generalizability of the findings. Second, only a single postoperative time point was evaluated; longitudinal assessment would provide deeper insight into muscle mass trajectories. Third, muscle quality (e.g., myosteatosis) and objective functional measures (e.g., grip strength and gait speed) were not assessed, preventing a comprehensive evaluation of sarcopenia. Future multicenter prospective studies incorporating both quantity and quality of muscle as well as functional parameters are warranted to validate these findings.

Conclusions

Low absolute SMM at 6 months after gastrectomy was an independent predictor of poor OS, whereas ΔPMI was not prognostic. Absolute SMM at this physiologically stable mid-term postoperative stage may reflect host resilience and systemic frailty and could serve as a practical marker for long-term risk stratification in patients undergoing gastrectomy for gastric cancer.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-1-976/rc

Data Sharing Statement: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-1-976/dss

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-1-976/prf

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-2025-1-976/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. The study was reviewed and approved by the Institutional Review Board of the Nihon University Itabashi Hospital (No. RK-211012-6) and was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Given the retrospective nature of the study, the requirement for written informed consent was waived by the Institutional Review Board, and an opt-out method was used to obtain participants’ consent.

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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