Fu B, Hu L, Ji H, Hou YF. New research progress of sarcopenia in surgically resectable malignant tumor diseases. World J Clin Oncol 2025; 16(4): 100309 [DOI: 10.5306/wjco.v16.i4.100309]
Corresponding Author of This Article
Ya-Feng Hou, Department of Hepatobiliary Surgery, Tongling People's Hospital (Tongling Hospital Affiliated to Bengbu Medical University), No. 468 Bijiashan Road, Tongguan District, Tongling 244000, Anhui Province, China. 19855755501@163.com
Research Domain of This Article
Surgery
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Bing Fu, Lei Hu, Hui Ji, Ya-Feng Hou, Department of Hepatobiliary Surgery, Tongling People's Hospital (Tongling Hospital Affiliated to Bengbu Medical University), Tongling 244000, Anhui Province, China
Author contributions: Fu B and Hu L prepared this manuscript; Ji H performed the literature research; Hou YF played indispensable roles in the study design and manuscript preparation as the corresponding authors; Fu B conceptualized, designed and supervised the whole process of the study; Hu L was responsible for language polishing and literature search; this collaboration between Ji H and Hou YF is crucial for the publication of this manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ya-Feng Hou, Department of Hepatobiliary Surgery, Tongling People's Hospital (Tongling Hospital Affiliated to Bengbu Medical University), No. 468 Bijiashan Road, Tongguan District, Tongling 244000, Anhui Province, China. 19855755501@163.com
Received: August 13, 2024 Revised: January 23, 2025 Accepted: March 6, 2025 Published online: April 24, 2025 Processing time: 225 Days and 2.4 Hours
Abstract
With the aging global population, the decline in muscle mass and function among the elderly has emerged as a significant concern. This systemic progressive generalized loss of muscle function and mass is referred to as sarcopenia (SP). In recent years, a growing number of studies have investigated SP, revealing that many tumor diseases, especially in the digestive system, promote its occurrence due to the influence of the disease itself, diet, and other factors. Moreover, SP patients tend to have poorer postoperative recovery. At present, many diagnostic methods have been developed for SP, but no unified standard has been established. Furthermore, the cutoff values of many diagnostic methods for different populations are still in the exploratory stage, and additional clinical studies are required to explore these issues. This article comprehensively and systematically summarizes the diagnostic methods and criteria mentioned in previous research, focusing on the impact of SP on post-surgical patients with various malignant tumors.
Core Tip: Nowadays, more and more people have begun to pay attention to sarcopenia (SP), especially whether patients with SP before surgery have an impact on their short, long-term results after surgery is the focus of current research. Previously, we found that the diagnostic methods and diagnostic criteria of SP were quite different, and the incidence of SP was also different. This article provides a comprehensive review of the current relationship between SP and cancer.
Citation: Fu B, Hu L, Ji H, Hou YF. New research progress of sarcopenia in surgically resectable malignant tumor diseases. World J Clin Oncol 2025; 16(4): 100309
In 1989, Rosenberg first introduced the term “sarcopenia (SP)” to describe the age-related loss of muscle mass[1]. Subsequently, SP was defined as the decline in skeletal muscle mass and strength that occurs with aging[2]. However, no standard definition has been established in research and clinical practice[3,4]. In 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a globally accepted definition of SP: SP is a syndrome characterized by progressive and systemic loss of skeletal muscle mass and function[5]. This definition indirectly facilitates the identification and care of patients at potential risk of SP[6]. In early 2018, the European Working Group held its second meeting (EWGSOP2)[7] and proposed that SP is a progressive and systemic skeletal muscle disease, resulting in an increased risk of adverse consequences such as falls, fractures, and mortality. The meeting also used muscle strength reduction as the main reference indicator for SP, as scholars recognized that strength is a better predictor of adverse outcomes[8]. Moreover, the European Working Group concluded that muscle strength is currently the most reliable indicator for measuring muscle function[7,9]. In contrast to the definition of Western countries, the Asian Working Group for Sarcopenia (AWGS) proposed in 2019 that all muscle atrophy should be regarded as SP and that SP is an age-related disease with reduced skeletal muscle mass associated with decreased muscle strength and/or decreased physical performance[10]. The present article compares the definitions of SP between the East and the West. Despite some differences, they are essentially similar, emphasizing muscle mass and strength.
EPIDEMIOLOGY
Regional and racial differences contribute to the differences in diagnostic methods for SP, which partly explains the wide variability in prevalence. According to the 2019 AWGS report, epidemiological studies in Asian countries revealed that the prevalence of SP ranged from 5.5% to 25.7%, with men accounting for the majority (5.1%-21.0% for men and 4.1%-16.3% for women)[10]. Furthermore, the prevalence of SP is as high as 29% among the elderly in community medical institutions, showing a prevalence of 11% to 50% in people aged 80 years and above[11,12]. With the rapid growth in the number and proportion of elderly people worldwide, SP affects an increasing number of individuals[13]. Data from an Italian nursing home showed that approximately 32.8% of residents suffered from SP. The study suggested that SP is very common among residents of nursing homes, affecting more men (68%) than women (21%)[14,15]. A 10-year follow-up cohort study of community-dwelling elderly people from Brazil indicated that the overall prevalence of SP was 6.8%-17.4%[16]. Japanese scholars reported an overall prevalence of SP in their study population of 8.1%, with male and female prevalence rates of 10.1% and 7.2%, respectively[17]. A study in the United States on participants with an average age of 70.1 years found a prevalence of 36.5%[18,19]. In addition, a study in China showed a prevalence of 6.5% in males and 3.3% in females for SP defined according to EWGSOP2 (male: 6.5%; female: 3.3%). And 10.9% in males and 8.0% in females for SP defined according to the AWGS[20].
PATHOGENIC FACTOR
At present, the causes of SP and its underlying mechanism remain incompletely understood due to its complexity.
On the macroscopic level
(1) Studies have shown that the leading cause of SP is lack of physical exercise, which results in a gradual decrease in the number of muscle fibers gradually decreases from about 50 years old[21]. Additionally, individuals with a sedentary lifestyle show a more significant decline in muscle fiber and strength compared to those with more physical activity[22]; (2) The concentration of related hormones, including growth hormone, testosterone, and insulin-like growth factor, also decreases with age, indirectly leading to the loss of muscle mass and mass[22,23]; (3) Malnutrition leads to increased saturated fat in muscle and increased risk of atherosclerosis[24]; (4) A decrease in motor units that control muscles is observed with age; and (5) Decreased caloric intake, increased fibrosis progression, changes in muscle metabolism, and other factors[25].
At the molecular level
(1) Significant muscle wasting may result from increased breakdown signals from pro-inflammatory cells and reduced hormone synthesis signals. Studies have shown high levels of tumor necrosis factor α and interleukin-6 in the skeletal muscle of the elderly, which are common pro-inflammatory factors[22,26]; (2) The deposition of lipofuscin and crosslinked protein in skeletal muscle may result in reduced muscle strength in SP patients[27]; (3) Myostatin protein produced and released by muscle cells inhibits muscle production by inducing the formation of transforming growth factor β complex of SMAD transcription, thereby altering protein and influencing muscle cell function[28]; (4) PGC-1α is a transcriptional co-activator[29] that enhances mitochondrial function and inhibits the transcriptional activity of FoxO (a key family of proteins that regulate gene expression in cell growth, proliferation, differentiation and lifespan), which is inhibited by the myostatin protein[28,30]; (5) High-fat diet can affect the composition and structure of skeletal muscle and satellitecells (SC). These cells are responsible for muscle repair and regeneration after exercise[31]. Therefore, excessive fat deposition interferes with skeletal muscle production by altering the liver growth factor signaling pathway. This protein attaches to the extracellular matrix and is released after physical activity to repair tissue damage following exercise and activate SCs. Therefore, the lack of physical activity and an unbalanced diet are key factors that promote obesity and fat infiltration into muscle fibers and the liver[32]; and (6) The production of nitric oxide (NO) increases with physical activity and is a key signal for HGF activation. Thus, alterations in HGF signaling may result in decreased SC activation, which leads to incorrect repair fibers[33]. Meanwhile, a lack of physical exercise causes a reduced production of NO, which affects the release of HGF from the extracellular matrix. Hence, SCs are kept in the G0 phase of the cell cycle, leading to a decrease in the number of SCs[32].
DIAGNOSTIC METHODS AND CRITERIA OF SP
Calf circumference measurement
The maximum circumference of both legs is measured using an inelastic tape. This method is widely used in the screening of SP, facilitating the clinical diagnosis of community residents[34]. The AWGS2019 indicates that the method has moderate to high sensitivity and specificity in predicting SP or low skeletal muscle mass. A cut-off of calf circumference (CC) < 34 cm for men and < 33 cm for women is recommended for screening or case discovery in Table 1[10]. The EWGSOP2 mentions that the measurement of CC can be used as a diagnostic indicator for the elderly, with a cut-off point of < 31 cm[7].
This is a relatively accurate method and one of the most frequently used imaging techniques. This method can measure the composition of the whole body and the local area with a small amount of radiation. However, only fat-free body weight can be measured, while the overall muscle mass cannot be determined. In addition, a variety of different hardware and software packages are proposed by different manufacturers, leading to inconsistencies between machines, which also limits their comparability[35]. According to the study by Studenski et al[36], the appendicular skeletal muscle mass (ASM) is less than 20 kg for males and less than 15 kg for females. The EWGSOP2 recommends applying the standard proposed by Bennett et al[30] ASM < 20 kg for males and < 15 kg for females. The AWGS2019 recommends < 7.0 kg/m2 for males and < 5.4 kg/m2 for females.
Bioelectrical impedance analysis
It estimates body composition by calculating the difference in electrical conductivity between different tissues (e.g., bone, fat, muscle, cartilage)[37]. This method is an easy and convenient way to identify patients with SP in clinical practice, and provides an affordable, non-invasive test that can be completed in a few minutes during an outpatient visit. Compared with Dual-energy X-ray absorption (DEXA), bioelectrical impedance analysis (BIA) can be performed quickly, is easy to operate, non-invasive and non-radiative[38]. According to the AWGS2019 guidelines, home BIA devices are not recommended due to their low diagnostic accuracy, and multi-frequency BIA (all precisely adjusted) is recommended to measure muscle mass[10]. The AWGS2019 currently recommends a cut-off of < 7.0 kg/m2 for males and < 5.7 kg/m2 for females. Aleixo et al[38] proposed a cut-off of < 10.75 kg/m2 for males, < 6.75 kg/m2 for females.
Computed tomography
It is often used in the study of SP, especially in the oncology population. In most cases, cross-sectional images at the level of the third lumbar vertebra (L3) are analyzed for diagnosis[39]. Plain and enhanced abdominal computed tomography (CT) scans are performed to measure the skeletal muscle area in this plane. The skeletal muscle index (SMI) is calculated by dividing the total skeletal muscle area in cm2 by the height in m2, and the SMI is used to determine the patient's muscle mass. The study by Prado et al[40] showed that the cut-off SMI based on CT scans < 52.4 cm2/m2 for men and < 38.6 cm2/m2 for women. According to the standards of the International Consensus on Cancer Cachexia, the cut-off for SMI was < 55 cm2/m2 for men and < 39 cm2/m2 for women[41]. Kim et al[42] reported a SMI cut-off of < 49 cm2/m2 for men and < 31 cm2/m2 for women. A recent meta-analysis revealed that the SMI cutoff values mostly lie between 52-55 cm2/m2 for men and 39-41 cm2/m2 for women[43].
Magnetic resonance imaging
Due to its minimal radiation exposure and better soft tissue contrast, magnetic resonance imaging (MRI) can provide better clinical benefits than CT and may become the preferred imaging modality in the future[44]. A study from Khan et al[45] showed that both CT and T2WMRI can reproducibly segment the skeletal muscle area in the middle of the L3 level, with the two methods showing a strong correlation. T2W MRI can be used interchangeably with CT for the assessment of abdominal skeletal muscle area and SP. However, current research on MRI is limited to cadavers and imaging protocols, reference data, and thresholds have not yet been established[46].
Ultrasound
In a study from Berger et al[47], they first obtained ultrasound images of the rectus femoris muscle in the middle of the thigh and used instrument to measure the thickness and ultrasound density of this segment to assess muscle mass in the elderly. CT scans and magnetic resonance imaging are highly accurate, but both methods are expensive and imply exposure to ionizing radiation. Ultrasound is often superior to large equipment due to being small and portable and can dynamically assess soft tissue types[47]. Currently, studies investigating the role of ultrasound in SP are scarce, and population-based data on SP are lacking[48].
D3-creatine dilution method
Creatine is a guanidine compound that can be absorbed by muscle cells and excreted from the body in the urine by conversion to creatinine. Therefore, D3-creatine levels can be detected in collected urine samples[48]. This method can accurately measure the amount of creatine and skeletal muscle mass, but the technology is time-consuming, involves complex calculations, and has not yet been widely applied in clinical practice.
Questionnaire
The Simple five-item Rating Questionnaire (SARC-F) was proposed by Malmstrom and Morley[49]. It evaluates muscle strength, assistance walking, chair rise test, stair climbing, and number of falls. This method is widely used by clinicians due to its simplicity and inexpensive nature[49]. Studies have shown that SARC-F has good sensitivity and specificity in predicting muscle mass[50].
The 2018 EWGSOP2 recommends a discovery-assessment-confirmation-severity pathway for use in clinical practice and research. The protocol first uses a simple five-item scoring questionnaire to identify potential SP patients. Secondly, muscle strength is assessed using the grip strength and chair stand test. Then DXA, BIA, or CT is performed to evaluate muscle quantity or quality to confirm whether there is SP. Finally, physical fitness tests are performed to assess the severity of SP. Notably, the protocol proposes: Grip strength for men < 27 kg, women < 16 kg; chair stand > 15 seconds/5 rises; limb skeletal muscle mass for men < 20 kg, women < 15 kg; gait speed ≤ 0.8 m/second; SPPB ≤ 8 points; TUG ≥ 20 second; 400 m walk test - not completed or completed ≥ 6 minutes)[7].
The 2019 AWGS recommends the use of community preliminary screening and clinical diagnosis. The diagnostic indicators for preliminary screening in the community are: (1) CC (male < 34 cm, female < 33 cm) or SARC-F ≥ 4; and (2) Grip strength (male < 28 kg, female < 18 kg) or chair stand > 12 seconds/5 rises. Clinical diagnosis is based on muscle strength, muscle function and skeletal muscle mass of the limbs: Muscle strength-grip strength (male < 28 kg, female < 18 kg), muscle function (six-meter gait speed < 1.0 m/second or chair stand > 12 seconds/5 rises or SPPB ≤ 8 points), skeletal muscle mass of the limbs (DEXA male < 7.0 kg/m2, female < 5.4 kg/m2 or BIA male < 7.0 kg/m2, female < 5.7 kg/m2). SP is diagnosed by low skeletal muscle mass combined with low muscle strength or function; severe SP is diagnosed in the presence of all three parameters[10].
SP AND CANCER
Liver cancer
In a recent review paper, Perisetti et al[50] mentioned that SP has been increasingly considered as a predictive indicator for assessing the prognosis of patients with liver cancer. A growing number of studies have investigated its role in local, surgical, transplantation, and systemic treatment of patients with hepatocellular carcinoma. Early identification of SP and methods to improve muscle volume, strength, and quality can affect the patient's prognosis and overall survival (OS) time. Appropriate nutritional support, physical activity, or a combination of both may improve the muscle volume of these patients[50,51]. Gallo et al[51] further studied the pathophysiology of SP in liver cancer, proposing that malabsorption, hyperammonemia, metabolic changes, hormone defects, and increased systemic muscle loss all promote the occurrence of SP. In addition, SP can lead to decreased renal function based on blood creatinine, which is due to reduced liver creatinine production on the one hand and reduced creatinine conversion rate due to reduced systemic muscle content on the other hand[51,52]. A study in Wenzhou, showed that patients with hepatocellular carcinoma and SP had a higher 1-year mortality rate after liver resection compared to patients without SP (P = 0.043). Moreover, preoperative SP can reduce the postoperative survival rate and health-related quality of life of patients with liver cancer[52,53]. Another study from Beumer et al[54] summarized the impact of SP on the survival rate of liver transplant patients with hepatocellular carcinoma beyond the Milan criteria from multiple centers around the world. The study reported a 5-year OS difference of 11% between patients with SP and those without SP[54]. In addition, data from a European study showed that patients with SP who required surgical treatment for liver cancer required a higher amount of blood transfusion during surgery; however, no statistically significant difference was found between the two groups in terms of long-term survival outcomes and tumor recurrence after surgery[55].
Lung cancer
Evidence on the association between SP and outcomes in lung cancer patients varies from study to study. Chinese scholar Yang et al[53] hopes to systematically evaluate the effect of SP on lung cancer prognosis through meta-analysis. A total of 13 studies (1810 participants) were included in this analysis. The incidence of SP in patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) was 43% and 52% respectively. In lung cancer patients, SP was associated with shorter OS [hazard ratio (HR) 2.23; 95%CI: 1.68-2.94]. This association was found in both NSCLC (HR 2.57; 95%CI: 1.79-3.68) and SCLC (HR, 1.59; 95%CI: 1.17-2.14). In addition, SP was identified as an independent predictor of shorter OS in both stage I-II NSCLC (HR, 3.23; 95%CI: 1.68-6.23) and stage III-IV NSCLC (HR, 2.19; 95%CI: 1.14-4.24). However, SP was not an independent predictor of disease-free survival in NSCLC patients (HR, 1.28; 95%CI: 0.44-3.69). Finally, the research concluded that SP is common in lung cancer patients (approximately one-half) and is an important predictor of impaired OS in patients with SCLC or NSCLC of different stages[53]. A research team from the United States retrospectively analyzed patients who underwent anatomical lung resection for NSCLC between 2010 and 2019. In that study, SP was defined by calculating the cross-sectional area of skeletal muscle at the level of the fifth thoracic vertebra (T5). The results indicated that sarcopenic men showed poorer OS [41.0 (13.8-53.7) months; 42.0 (23.1-55.1) months, P = 0.023] and disease-free survival [15.8 (8.4-30.78) months; 34.8 (20.1-50.5) months, P = 0.007] compared with non-sarcopenic men. Nonetheless, no difference in survival was observed between sarcopenic and non-sarcopenic women when assessed at the T5 level[56].
Pancreatic cancer
Patients who undergo pancreaticoduodenectomy (PD) typically require long hospital stays and are at risk of many complications. Therefore, strategies to improve preoperative risk stratification are crucial, and SP has emerged as a risk factors. Pessia et al[57] retrospectively analyzed SP in patients undergoing PD to evaluate its importance as a preoperative risk factor. The study retrospectively identified 76 consecutive patients who underwent PD for pancreatic cancer. The results revealed that SP may be a useful preoperative prognostic factor for patients undergoing PD for pancreatic cancer. Disease-free survival may be affected by the presence or absence of SP before surgery; the average hospital stay for patients with SP and non-SP was 21 days and 17 days, respectively. Moreover, the average hospital stay for patients with SP was 20% longer than that for patients without SP. The team concluded that SP was associated with poor surgical outcomes and proposed that SP in cancer patients could impact postoperative outcomes, OS, and long-term survival outcomes[57]. Another study also mentioned that SP is an independent risk factor for increased 3-year mortality in patients undergoing PD (HR = 1.63, P < 0.001). The study showed a 63% increase in the 3-year mortality risk of patients with SP and proposed that SP is an objective indicator of the patient's physical condition and is closely related to long-term outcomes independent of tumor-specific factors[58].
Gastric cancer
SP is prevalent in patients with gastrointestinal malignancies, including gastric cancer, but data from Eastern and Western populations are lacking. Sierzega et al[59] retrospectively analyzed clinical data from 138 Caucasian patients who underwent gastrectomy for gastric adenocarcinoma between 2012 and 2015 to assess the impact of SP. A total of 60 out of 138 patients (43%) had SP. SP was associated with postoperative morbidity (43% vs 23%, P = 0.011), major postoperative complications (Clavien-Dindo ≥ 3a, 36% vs 21%, P = 0.035) and reoperation (23% vs 9%, P = 0.020). Patients with SP had longer postoperative hospital stays (8.0 days vs 6.5 days, P = 0.010). The overall median survival time of patients with SP was significantly lower than that of patients with normal skeletal muscle (11.0 months vs 36.7 months, P = 0.005). SP was an independent prognostic factor with an OR of 1.94 (95%CI: 1.08-3.48, P = 0.026). Finally, they concluded that SP is associated with increased postoperative morbidity and impaired long-term survival[59]. Another study by Sugiyama et al[60] explored the relationship between SP and prognosis in metastatic gastric cancer (mGC) patients receiving chemotherapy[60]. This study retrospectively analyzed 231 Japanese mGC patients who received first-line chemotherapy from January 2013 to December 2015. SP was defined as a decrease in SMI ≥ 10% during chemotherapy, and its correlation with treatment failure (TTF) and OS was evaluated. The results revealed that SP is significantly associated with shorter TTF and OS and is an independent prognostic factor for these two parameters[61].
Colorectal cancer
In patients with colorectal cancer, the prevalence of SP ranges from 12% to 60%[62]. Studies have found that SP is associated with higher postoperative morbidity and poorer tumor prognosis in patients undergoing colorectal cancer surgery, but most studies have been limited by small sample sizes or short follow-up times[63]. A study from Schneider et al[63] aimed to assess the association of muscle loss signs with short-term clinical outcomes after colon cancer surgery. The study through three imaging indexes [skeletal muscle area (SMA), SMI, skeletal muscle radiation attenuation (SMRA)] to describe reduce muscle disease, and further explained the relationship between the class indexes and postoperative effect. A total of 325 patients were included in the study. The mean age was 67 years and the mean body mass index was 26.0 kg/m2. Of 193 cases (59%) were male. Serious complications occurred in 50 cases (15.4%) and no serious complications occurred in 275 cases (84.6%). There were no statistically significant differences in SMA and SMI between the two groups, while SMRA was significantly lower in patients with severe complications. Finally, the results show that SMRA, as a specific marker of SP, seems to be superior to SMA and SMI in predicting postoperative adverse outcomes in patients with severe complications of colon cancer[64]. Another study from the United States also looked at the relationship between SP and postoperative complications, length of hospital stay, readmission rates, and mortality in colon cancer patients. The study assessed SMI and skeletal muscle radiation density (SMD) levels using preoperative CT images. The mean age of patients at diagnosis was 64.0 years, and 906 (55.6%) were female. Studies have shown that patients with low SMI or low SMD are more likely to have a longer hospital stay after surgery and a higher risk of death. In addition, patients with low SMI are more likely to develop one or more postoperative complications and have a higher risk of 30-day death[65]. In addition, a study from Wuhan Union Medical College Hospital in China investigated the correlation between CT quantitative skeletal muscle and fat and postoperative complications and long-term prognosis in patients with rectal cancer. A total of 415 patients were included in the study, including 240 males and 175 females. The mean age was (57.8 ± 10.5) years. The results show that at L3 level, high SMD and high SMI are significantly correlated with longer OS and DFS, while at umbilical level, inter muscular fat area and low SMI are significantly correlated with poorer OS and DFS[66].
Carcinoma of bladder
Recently, a team of researchers from Seoul, South Korea reviewed the association between preoperative SP and long-term outcomes in patients undergoing radical cystectomy for bladder cancer. The team's clinical data were followed for a median of 104 months. SP was present in 37.9% of patients. Although there were no significant differences in postoperative pathologic outcomes between the SP and non-SP groups, SP was significantly associated with poorer oncology outcomes. Compared with the non-SP group, the SP group had a lower OS rate (52.0% vs 67.1% at 5 years, 35.5% vs 52.7% at 10 years) and a higher mortality rate (63.3% vs 74.3% at 5 years, 50.7% vs 67.4% at 10 years). They further studied and analyzed that SP, body mass index, tumor stage, lymph node metastasis, and lymphovascular invasion were all independent predictors of survival[67]. In addition, a multicenter study by Mayr et al[68] here also verified that SP was an independent predictor of oncological outcomes after radical cystectomy for bladder cancer. In this study, 189 patients (37.8%) were defined as SP based on SMI. The SP group was older than the non-SP group (P = 0.002), but there was no statistically significant difference between the two groups in terms of gender, comorbidities, TNM stage, and urinary diversion type (P > 0.05). There were 234 deaths (46.8%), of which 145 (29.0%) were due to bladder urothelial carcinoma. The 5-year OS of SP patients was significantly worse (38.3% vs 50.5%, P = 0.002), 5-year cancer-specific survival (49.5% vs 62.3%, P = 0.016) was significantly higher than those in patients without SP[68].
Other types of tumors
In a literature review, we found a study by Yoshimura et al[69] in Japan on the association between oral squamous cell carcinoma and muscle loss, and concluded a different study method. They argue that most studies use CT images to measure cross-sectional skeletal muscle mass at the level of the third lumbar vertebrae, and patients with head and neck squamous cell carcinoma are not routinely prepared for abdominal CT, so the team investigated whether skeletal muscle mass in the neck muscles is associated with postoperative survival in patients with oral squamous cell carcinoma. Finally, it is concluded that assessing SP by assessing preoperative cervical skeletal muscle mass and quantity may help optimize the treatment of patients with oral squamous cell carcinoma, and the prognosis of patients with poor cervical muscle quantity and quality is not satisfactory[69]. Another article by Salati et al[70] evaluated the effect of preoperative CT-based skeletal muscle mass reduction on postoperative clinical outcomes and survival in patients undergoing total laryngectomy due to cancer. A total of 84 patients were included in the study, 37 of whom had pre-operative skeletal muscle mass loss. There were no significant differences in the incidence of postoperative fistula (23% vs 35%, P = 0.348), cervical skin dehiscence (17% vs 11%, P = 0.629), superficial incision surgical site infection (12% vs 10%, P = 1.000), and unplanned reoperation (38% vs 37%, P = 1.000) between the two groups. There was no difference in the median length of stay between the two groups (41 days vs 33 days, P = 0.295), nor in the cost of treatment [119976 Swiss francs (CHF) vs 109402 CHF, P = 0.585]. Median OS was comparable between the two groups (3.43 years vs 4.95 years, P = 0.09). Finally, studies have shown that decreased skeletal muscle mass alone has no significant effect on postoperative clinical outcome or survival[70].
TREATMENT OF SP
The occurrence of SP is primarily related to two factors, namely “reduced production and increased consumption”. On the one hand, the patient's advanced age, liver dysfunction caused by the disease itself, and malnutrition due to impaired gastrointestinal digestion and absorption cause a decrease in skeletal muscle production. On the other hand, long-term insufficient nutritional intake leads to increased consumption of the body itself. The appearance of SP also reflects the patient's nutritional issues. Furthermore, malnutrition increases the risk of complications after surgery. Additional research on this type of patient, may increase awareness of the need for nutritional support treatment after hospitalization, such as intravenous nutrition and even nasoenteric tube nutrition support.
The European SP Working Group has shown early and aggressive intervention can effectively promote the prevention, delay, treatment, and even reversal of SP. The latest recommendations of the working group are aimed at increasing awareness of SP and its risks in the society. These new recommendations emphasize that patients at risk for SP should receive intervention measures against SP and minimize such adverse events. These include physical exercise, nutritional supplementation, hormone replacement, and therapeutic drugs that promote muscle mass. However, most studies have been conducted in non-cancer patients, and relatively limited studies have focused on cancer patients[7,71].
As reported by Kwak and Kwon[61], several drugs currently under investigation that may be effective against SP, including anti-myostatin antibodies (Stamulumab and Trevogrumab), activin receptor agonists (Bimagrumab), and selective androgen receptor modifiers (Enobosarm). However, the report states that the results of large-scale Phase III clinical trials are still being validated, and no treatments has been approved for SP yet[71].
According to the AWGS2019 report, proper exercise combined with nutritional support can improve muscle strength and function, and also help muscle mass. The protocol also mentions that certain drugs may significantly increase ASM and functional performance, but the potential clinical benefit remains uncertain[10,72].
CONCLUSION
With the aging of the population, the incidence of SP also increases. Early diagnosis, early prevention, and early intervention are the cornerstone of addressing SP. At present, the mechanism of SP has been mostly clarified, but many unresolved issues remain. The definition of SP in oncology has not yet been standardized; whether the diagnostic criteria for SP should be based on the disease remains controversial. In addition, for patients scheduled for surgical intervention for tumor resection, the effect of SP on the patient's short-term recovery and long-term results should be further studied. Considering that SP may be correlated with the patient's postoperative outcomes, preventing and treating SP holds clinical significance. The continuous advances in surgical instruments, equipment, and surgical techniques facilitate the surgical treatment of tumor patients, but poor postoperative results hinder the development of surgery. This paper, emphasizes the importance of SP in cancer patients and prompts further study of the impact of SP in patients with resectable tumors.
ACKNOWLEDGEMENTS
We are grateful to all of the study participants whose work made this study possible.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Oncology
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade D
Novelty: Grade C
Creativity or Innovation: Grade C
Scientific Significance: Grade C
P-Reviewer: Xiao MZ S-Editor: Li L L-Editor: A P-Editor: Zhao YQ
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