Sarcopenia as a poor prognostic indicator for renal cell carcinoma patients undergoing nephrectomy in China: A multicenter study

Dear Editor, We conducted a multicenter clinical study to investigate the effect of sarcopenia on survival of Chinese population after nephrectomy for renal cell carcinoma (RCC). Lumbar skeletal muscle index (SMI) and total psoas index (TPI) measured by preoperative computed tomography were used to assess sarcopenia. Andwe found that sarcopenia was a poor prognostic indicator of overall survival (OS) and cancer-specific survival (CSS). RCC is one of the most common malignancies in the urinary system and also the most common renal malignant tumor originating from the kidney, accounting for 80-85% in renal malignant tumors and 2-3% in systemic malignancies.1 For patients with localized RCC, radical or partial nephrectomy is the most common treatment. For patients with advanced metastatic RCC, comprehensive treatments such as molecular replacement therapy and immunotherapy are widely used.2 Sarcopenia, also known as skeletal muscle loss, is a progressive and extensive skeletal muscle disease characterized by reduced skeletal muscle mass and decreased muscle function.3 Many current studies have confirmed that the occurrence of sarcopenia is closely associated with the treatment and prognosis of many resectable malignant tumors.4 Sarcopenia can reduce the treatment tolerance of tumor patients, increase the toxic reaction of antineoplastic drugs, prolong the length of hospital stay, and increase postoperative complications, which is the index of poor prognosis of tumor patients after operation.5 For patients with RCC, the prognostic value of sarcopenia is still controversial. Sharma et al6 and Fukushima et al7 found that sarcopenia is an OS-related factor for patients with metastatic RCC (mRCC) who have received cytoreductive nephrectomy or cytokine therapy and targeted agents. However, Peyton et al8 found that sarcopenia was not associated with OS in advanced RCC patients who have received radical nephrectomy. Furthermore, there are


Sarcopenia as a poor prognostic indicator for renal cell carcinoma patients undergoing nephrectomy in China: A multicenter study
Dear Editor, We conducted a multicenter clinical study to investigate the effect of sarcopenia on survival of Chinese population after nephrectomy for renal cell carcinoma (RCC). Lumbar skeletal muscle index (SMI) and total psoas index (TPI) measured by preoperative computed tomography were used to assess sarcopenia. And we found that sarcopenia was a poor prognostic indicator of overall survival (OS) and cancer-specific survival (CSS).
RCC is one of the most common malignancies in the urinary system and also the most common renal malignant tumor originating from the kidney, accounting for 80-85% in renal malignant tumors and 2-3% in systemic malignancies. 1 For patients with localized RCC, radical or partial nephrectomy is the most common treatment. For patients with advanced metastatic RCC, comprehensive treatments such as molecular replacement therapy and immunotherapy are widely used. 2 Sarcopenia, also known as skeletal muscle loss, is a progressive and extensive skeletal muscle disease characterized by reduced skeletal muscle mass and decreased muscle function. 3 Many current studies have confirmed that the occurrence of sarcopenia is closely associated with the treatment and prognosis of many resectable malignant tumors. 4 Sarcopenia can reduce the treatment tolerance of tumor patients, increase the toxic reaction of antineoplastic drugs, prolong the length of hospital stay, and increase postoperative complications, which is the index of poor prognosis of tumor patients after operation. 5 For patients with RCC, the prognostic value of sarcopenia is still controversial. Sharma et al 6  We conducted a large retrospective multicenter study among the Chinese population from three hospitals between January 2014 and December 2019 to evaluate the effect of sarcopenia on OS and CSS in patients with RCC undergoing nephrectomy. Sarcopenia was assessed with lumbar SMI and TPI measured by computed tomography within 1 month before surgery. About TPI, the total psoas area (TPA, mm 2 ) on both sides of the L3 axial plane was assessed, and then the TPI (TPI = TPA/(height (m) × height (m))) was normalized to the patient's height. About SMI, the skeletal muscle area (SMA, cm 2 ) is the total muscle area of the psoas, paraspinal, internal oblique, external oblique, rectus abdominis, and transversus abdominis muscles on both sides ( Figures 1A-1C), and then SMI (SMI = SMA/(height (m) × height (m))) was normalized to height. Patients with TPI < 545mm 2 /m 2 in male or TPI < 385mm 2 /m 2 in female can be diagnosed as sarcopenia. 9 Patients in female with SMI < 41cm 2 /m 2 or in male with SMI < 43cm 2 /m 2 and body mass index (BMI) < 25 kg/m 2 or with SMI < 53cm 2 /m 2 and BMI ≥25 kg/m 2 can be diagnosed as sarcopenia. 10 When the TPI was used as an assessment criterion for sarcopenia, a total of 97 patients (21.9%) could be assessed as sarcopenia (Table 1). When the SMI was used as an evaluation criterion for sarcopenia, 157 patients (35.4%) were assessed as sarcopenia. In the entire cohort, the mean age of patients was 58.02 years, and the gender was predominantly male (66.8%). The proportion of female patients and over 65 years patients in the sarcopenia group was higher than that in nonsarcopenia group, but the difference observed when TPI was used as an assessment criterion was not statistically significant (gender, P = .493; age, P = .237). Patients with sarcopenia had older age, lower BMI, and shorter survival time than nonsarcopenia patients. Due to the lower BMI of sarcopenia patients, we examined the relationship among TPI, SMI, and BMI. And then we found a significant correlation between SMI and BMI (R square = 0.321, P < .001; Figure 1D), TPI and BMI (R square = 0.0928, P < .001; Figure 1E), SMI and TPI (R square = 0.5067, P < .001; Figure 1F).
Smoothing splines curves showed that both TPI and SMI could reduce the risk of OS (Figures 2A and 2C) and CSS ( Figures 2B and 2D) as their values increased. As there are differences in gender, ethnic, and physical between Eastern and Western countries, we redefined the thresholds of TPI and SMI for the diagnosis of sarcopenia in Chinese patients with RCC (Table S1). In the total population, the thresholds for TPI and SMI were 574.1mm 2 /m 2 and 47.5cm 2 /m 2 , respectively (Figures 2A-2D).
To our knowledge, this is the largest and also the first multicenter study on the effect of sarcopenia to the prognosis of Chinese nephrectomy patients. And it shows that sarcopenia is a factor which can affect the poor prognosis of OS and CSS in nephrectomy patients.

C O N F L I C T O F I N T E R E S T
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

E T H I C S A P P R O VA L A N D C O N S E N T T O PA R T I C I PAT E
The methodology of this study followed the criteria outlined in the Declaration of Helsinki (as revised in 2013) and was ethically approved by the Ethics Committees and Institutional Review Boards of all participating institutions.

D ATA AVA I L A B I L I T Y S TAT E M E N T
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.