Serum creatinine and cystatin C-based diagnostic indices for sarcopenia in advanced non-small cell lung cancer

Abstract

Background: Sarcopenia is an important prognostic factor of lung cancer. The serum creatinine/cystatin C ratio (CCR) and the sarcopenia index (SI, serum creatinine × cystatin C-based glomerular filtration rate) are novel screening tools for sarcopenia; however, the diagnostic accuracy of the CCR and SI for detecting sarcopenia remains unknown. We aimed to explore and validate the diagnostic values of the CCR and SI for determining sarcopenia in non-small cell lung cancer (NSCLC) and to explore their prognostic values for overall survival.

Methods: We conducted a prospective cohort study of adult patients with stage IIIB or IV NSCLC. Levels of serum creatinine and cystatin C were measured to calculate the CCR and SI. Sarcopenia was defined separately using CCR, SI, and the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Participants were randomly sampled into derivation and validation sets (6:4 ratio). The cutoff values for diagnosing sarcopenia were determined based on the derivation set. Diagnostic accuracy was analysed in the validation set through receiver operating characteristic (ROC) curves. Cox regression models and survival curves were applied to evaluate the impact of different sarcopenia definitions on survival.

Results: We included 579 participants (women, 35.4%; mean age, 58.4 ± 8.9 years); AWGS-defined sarcopenia was found in 19.5% of men and 10.7% of women. Both CCR and SI positively correlated with computed tomography-derived and bioimpedance-derived muscle mass and handgrip strength. The optimal cutoff values for CCR and SI were 0.623 and 54.335 in men and 0.600 and 51.742 in women, with areas under the ROC curves of 0.837 [95% confidence interval (CI): 0.770-0.904] and 0.833 (95% CI: 0.765-0.901) in men (P = 0.25), and 0.808 (95% CI: 0.682-0.935) and 0.796 (95% CI: 0.668-0.924) in women (P = 0.11), respectively. The CCR achieved sensitivities and specificities of 73.0% and 93.7% in men and 85.7% and 65.7% in women, respectively; the SI achieved sensitivities and specificities of 75.7% and 86.5% in men and 92.9% and 62.9% in women, respectively. CCR-defined, SI-defined, and AWGS-defined sarcopenia were independently associated with a high mortality risk [hazard ratio (HR) = 1.75, 95% CI: 1.25-2.44; HR = 1.55, 95% CI: 1.11-2.17; and HR = 1.76, 95% CI: 1.22-2.53, respectively].

Conclusions: CCR and SI have satisfactory and comparable diagnostic accuracy and prognostic values for sarcopenia in patients with advanced NSCLC. Both may serve as surrogate biomarkers for evaluating sarcopenia in these patients. However, further external validations are required.

Keywords: Decision curve analysis; Lung cancer; Muscle depletion; Muscle wasting; Survival.

Figure 1

Violin plot and box‐plot analysis comparing the distribution of the CCR and SI in the sarcopenia and non‐sarcopenia groups. In both men and women, the (A) CCR and (B) SI were lower in the sarcopenia group than in the non‐sarcopenia group. CCR, serum creatinine/serum cystatin C ratio; SI, sarcopenia index.

Figure 2

ROC curves of the CCR and SI for diagnosing sarcopenia in the derivation set. AUC, area under the ROC curve; CCR, serum creatinine/serum cystatin C ratio; ROC, receiver operating characteristic; SI, sarcopenia index.

Figure 3

Decision curve analysis comparing the CCR and SI in the derivation (A) and validation (B) sets. No statistically significant difference was found between the CCR and SI for identifying sarcopenia. CCR, serum creatinine/serum cystatin C ratio; SI, sarcopenia index.

Figure 4

Survival curves for CCR‐defined, SI‐defined, and AWGS‐defined sarcopenia in the derivation and validation sets. Survival curves for CCR‐defined and AWGS‐defined sarcopenia statistically significantly differed in both the derivation (A,C) and validation (D,F) set via the log‐rank test. Survival curves for SI‐defined sarcopenia were not statistically significantly different in the derivation (B) and validation (E) sets. AWGS, Asian Working Group for Sarcopenia; CCR, serum creatinine/serum cystatin C ratio; SI, sarcopenia index.