Abstract
Purpose
To characterise (1) the definition and measurement methods of myosteatosis, (2) the impact of myosteatosis on post-operative complications (overall, severe complications defined as Clavien-Dindo 3 and above, anastomotic leak, length of stay) in both non-metastatic and metastatic colorectal cancer (CRC) patients and (3) the impact of myosteatosis on long-term survival outcomes in non-metastatic CRC (overall survival, cancer-specific survival, disease-free survival).
Methods
A systematic search of Medline, Embase and Cochrane Central databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in 2024.
Results
A total of 4410 publications were initially retrieved; 54 studies fulfilled the inclusion criteria. A variety of measurement methods of myosteatosis were found. There was good quality evidence to support a negative correlation between myosteatosis and overall survival (OS). Colon cancer was more consistently associated with OS and DFS compared to rectal cancer. Myosteatosis was found to significantly impact severe (Clavien-Dindo 3 and above) postoperative complications in colon cancer. Other postoperative outcomes were limited by inconsistency and an overall paucity in volume and quality.
Conclusion
Myosteatosis has a negative association with OS, with consistent effects observed in colon cancer. There is a negative association with severe postoperative outcomes, particularly in colon cancer. These results are limited by the risk of bias and heterogeneity in measurement methods and statistical analysis. Future work is required to clarify the scan acquisition protocol and diagnostic criteria.
Supplementary Information
The online version contains supplementary material available at 10.1007/s00384-025-05061-y.
Keywords: Myosteatosis, Body composition, Colorectal cancer, Survival, Postoperative
Introduction
Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide [1]. The prognostication, selection and preparation of patients for surgical and oncological care are important to ensure that we offer patients precision medicine and optimise individual patient survival and quality of life [2, 3]. Surgical management can have severe short-term complications such as infection, haemorrhage, anastomotic leakage and cardio-respiratory complications [4]. Such complications lead to increased morbidity for the patient as well as healthcare costs [5]. Emerging research suggests that patients’ body composition can serve as a prognostic indicator for postoperative recovery and survival.
Myosteatosis, the infiltration of fat within skeletal muscle, is a body composition parameter which increases with aging and has been associated with loss of muscle strength and function. It is thought to precede the development of metabolic disturbances, including insulin resistance and diabetes [6, 7]. Myosteatosis is distinct to sarcopenia (the loss of muscle mass), has independent prognostic effects and has been associated with poorer survival outcomes, prolonged hospitalisation and increased postoperative complications in CRC [8, 9]. Routinely performed computed tomography (CT) scans for oncological staging can provide an opportunistic method for the radiological assessment of myosteatosis in CRC patients.
This systematic review aimed to evaluate the following: (1) The definition and measurement methods of myosteatosis, (2) the impact of myosteatosis on post-operative complications (overall, severe Clavien-Dindo 3 and above, anastomotic leak, length of stay) in both non-metastatic and metastatic CRC patients and (3) the impact of myosteatosis on long-term survival outcomes in non-metastatic CRC (overall survival, cancer-specific survival, disease-free survival) in CRC.
Methods
Search strategy and study selection
This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic search was performed on Medline, Embase and Cochrane Central databases from inception up until 31 December 2024. Medical Subject Headings of the National Library of Medicine (MeSH) descriptors related to “colorectal cancer”, “body composition” or “myosteatosis” and “survival” or “postoperative complications” were combined with a broad range of modifiers. The search strategy was developed for MEDLINE and EMBASE and adapted for Cochrane with the aid of an experienced Health Sciences Librarian. The final search strategies are listed in full in the Appendix. Title and abstract screening and full-text review of all texts were conducted independently by two reviewers (CH and JZ), with disagreements resolved through consultation with a third reviewer (JY).
Inclusion criteria for all questions were: (i) patient population of primary colon and/or rectal adenocarcinoma patients, aged 18 and over; (ii) computed tomography images obtained pre-surgery; (iii) measurement of myosteatosis quantified on CT scans; (iv) outcomes of the study must be either postoperative complications and/or long-term survival outcomes, defined as overall survival (OS), recurrence-free survival (RFS) or cancer-specific survival (CSS). When selecting studies analysing survival outcomes, the significant impact of metastasis on prognosis was discussed among all reviewers and agreed to be a confounder [10, 11]. Thus, only studies examining non-metastatic (stage 0–III) CRC were included for this question. For analysis of postoperative outcomes, both non-metastatic and metastatic CRC were included. Studies were excluded if they: (i) omitted data on cancer stage of patients; (ii) lacked pre-operative CT scan acquisition; (iii) CT scans were acquired post-operatively; or (iv) lack of clear description of myosteatosis quantification on CT. Due to the large number of studies retrieved through the search, a best-evidence approach was employed after discussion between reviewers, and only studies with a sample size > 50 were considered for this review.
Data extraction and synthesis
Data extraction was performed by two reviewers (CH and JZ). Extracted study details included authorship, year of publication, country, patient characteristics, treatment regimens including chemo-/radiotherapy regimes, surgical procedures undergone by the patients, the measurement and definition of radiological myosteatosis and outcome data including OS, CSS and RFS. Postoperative outcomes included total complications, complication severity (with severe complications defined as a Clavien-Dindo score of 3 or greater), anastomotic leak and length of stay (LOS). Due to heterogeneity found in the assessment and definition of myosteatosis, patient clinical features including cancer type and treatment regimens and approaches to statistical analyses used among the studies, a meta-analysis was not performed.
The Newcastle–Ottawa Scale was used for assessment of the risk of publication bias of the included studies [12]. CH and JZ independently scored all studies and resolved discrepancies through discussion and escalation to JY where conflicts persisted. Benchmarks for each category were determined through discussion among all reviewers. A clear description of data sources was considered important for all studies. BMI, age, sex, tumour stage and type of surgery were considered important confounding variables, as was smoking, particularly for studies examining postoperative outcomes. A duration of 5 years was considered the standard for sufficient follow-up time in survival outcomes, given that this is the standard for follow-up of CRC internationally.
Results
A total of 4410 publications were retrieved, and after screening and full-text review, a total of 54 studies were found amenable for data extraction (Figure 1).
Fig. 1.
PRISMA flow chart
Study characteristics
Fifty-four studies employing an observational cohort study design were identified, from different regions across Europe, America and Asia (Table 1). Five were prospective, while the remaining were retrospective. Approximately equal gender splits (40–60% male) were found in all studies, and participant age ranged from 40 to 80 s, with a median age of 60–70 being common. The majority of studies specified whether participants had undergone neoadjuvant or adjuvant therapy and the type of surgery (emergency vs elective, open vs laparoscopic vs robot-assisted) performed. Most studies analysed colon and rectal cancer together. Follow-up periods varied from unspecified lengths of time to 10.2 years.
Table 1.
Study characteristics
| Study | Country | Study type | Number of participants | Characteristics of subjects (i.e. medium age, gender %) | Chemo- and/or radiotherapy (yes/no) | Type of surgery (i.e. elective vs emergency, open vs laparoscopic) | Measure of myosteatosis (SMD, IMT, IMAC) | Level of measurement (e.g. L3) | Cut-off value for myosteatosis | Muscles measured (i.e. total abdominal muscles vs psoas muscle only) | % myosteatosis |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Lee 2023[13] | South Korea | Retrospective cohort study | 616 | Median (interquartile) age was 64 (55–72) years; male (61.1%) | NO NCRT; some had adjuvant chemotherapy | Elective surgery only (no emergency) | SMD | L3 | Martin’s definition | TAMA | 32.40% |
| Lee 2023[14] | USA | Retrospective cohort study | 1766 | Mean age ± SD: 63.7 ± 14.4 years; 48.8% men | Unknown | Unknown | SMD | L3 | Lowest tertile of SMD (ALL: 34.6 HU); and continuous variable | TAMA | 58.30% |
| Kim 2023[15] | South Korea | Retrospective cohort study | 474 | Age ≥ 65: 58.6%; 54.2% male | Yes, adjuvant chemotherapy only; no, NCRT | Unknown | SMD | L3 | Male: < 24.01 HU; female: < 12.50 HU | TAMA | 24.30% |
| Cuijpers 2022[16] | Netherlands | Prospective cohort study | 238 | Mean age ± SD: 69.3 ± 9.9 years; male 56.3% | Yes, 21.4% had NCRT | Elective surgery only; open and laparoscopic | SMD | L3 | Martin’s definition | TAMA | 41.20% |
| Pacquelet 2022[17] | France | Retrospective cohort study | 202 | Mean age ± SD: 64.8 ± 11.4 [range 29–88]; Male 59.4% | Yes, NCRT | Open and laparoscopic | Intermuscular fat area (IMFA) | 4 levels: L2–L3 intervertebral disc; L3; and L3–L4 and L4–L5 intervertebral discs | Continuous variable | TAMA | Not stated |
| VanVugt 2018 [18] | Netherlands | Retrospective cohort study | 816 | Median age 79; 53.9% male | Yes, NCRT | Open and laparscopic | SMD | L3 | Martin’s definition | TAMA | 64.10% |
| Kemper 2023 [19] | Germany | Retrospective cohort study | 207 | Mean age ± SD: 65.0 ± 14.5 years; Male 59.4% | Yes, NCRT | laparoscopic or open | SMD | L3 | Survival analysis cut-off: median MRA (38 HU); postoperative complications cut-off: continuous variable | TAMA | 11.10% |
| Blackwell 2023[20] | UK | Retrospective cohort study | 1122 | Median age 70 [range 61–76]; Male 57.7% | Unknown | Elective surgery only | SMD | L3 | Martin’s definition | Psoas muscle | Not stated |
| Schaffler-Schaden 2020[21] | Austria | Retrospective cohort study | 85 | Median age (IQR) for males and females, respectively: 76 (67.5, 82); 75 (71, 82); male 56.5%, | Yes, chemotherapy | Elective surgery; both laparoscopic and open right colectomy | SMD | L3 | Martin’s definition | TAMA | Not stated |
| Pozzuto 2021 [22] | Brazil | Retrospective cohort study | 227 | Age > 65: 36.6%, male 44.9% | Yes, adjuvant chemotherapy and NCRT | Emergency and elective surgery | SMD; IMAT | L3 | Martin’s definition | TAMA | 66.10% |
| Looijaard 2020[23] | Netherlands | Retrospective cohort study | 378 | Median age: 73.4 (interquartile range 69.5–78.4); male (60.3%) | Yes, Adjuvant chemotherapy | Elective surgery | SMD; IMAT | L3 | No cut-off specified; continuous | TAMA | Not stated |
| Bimurzayeva 2024[24] | South Korea | Retrospective cohort study | 499 | No age statistics given for whole cohort; male 57.7% | No NCRT | Unknown | SMD | L3 | MALE: 34.8 HU; FEMALE: 33.9 HU | TAMA | Not stated |
| Xiao 2023[25] | China | Retrospective cohort study | 191 Rectal cancer | Mean age ± SD: 73.60 ± 8.81 years; 66.0% male | Yes, CRT | Open and laparscopic | SMD | L3 | Continuous variable | Psoas muscle only | Not stated |
| Tankel 2020[26] | Israel | Retrospective cohort study | 185 | Age > 75: 31.9%; 49.2% male, 50.8% female | Yes, adjuvant or NCRT | Laparoscopic right or extended right hemicolectomy | HUAC (measured as: ([right average HU*right psoas area]/[TPA] + [left average HU*left psoas area]/[TPA])/2) | Upper border of L3 | Lowest gender specific quartile (male, 44.5; female, 44.9) | Psoas muscle | 23.80% |
| Chung 2020[27] | South Korea | Retrospective cohort study | 167 | Age ≥ 65: 31.7%; 59.9% male, 40.1% female | Yes, adjuvant chemotherapy. No NCRT | Elective | SMD | L3 | Martin’s definition | TAMA | Not stated |
| Giani 2020[28] | Italy | Retrospective cohort study | 173 | Median age 71 (61–77); Male 64.2% | Yes- NCRT | Open and laparoscopic; anterior resection, Miles procedure or Hartmann’s procedure | Intramuscular fat area ratio (IMFAR = IMFA/TMA) | L3 | Lowest gender specific quartile (male, 0.28 cm2/m2; female, 0.37 cm2/m2) | TAMA | 25.00% |
| Giani 2022[29] | Italy | Retrospective cohort study | 129 | Median age 72 years (IQR 62–78); male 68.2% | Yes, adjuvant chemotherapy only | Open or laparoscopic | IMFAR = intramuscular fat area/total muscle area | Abdomen (unspecified level) | Last quartile of dataset (unspecified value) | TAMA | 64.10% |
| Carcamo 2021 [30] | Chile | Retrospective cohort study | 359 | Mean age ± SD: 64 ± 14.12 years; 193 men (54%) and 166 women (46%) | Yes, adjuvant chemotherapy | Open and laparoscopic | SMD | L3-L4 | Martin’s definition | TAMA | 22.30% |
| Ferreira 2024[31] | Brazil | Retrospective cohort study | 257 | Mean age ± SD 62.5 ± 12.1 years; 49.8% male | Yes | N/A | SMD = mean HU of both legs | Level of the lower margin of the lesser trochanter of the femur | Median value of sample’s data distribution | Quadriceps, pectineus, tensor fasciae latae, iliopsoas, sartorius, adductor longus, adductor brevis, adductor minimus, adductor magnus, gracilis, semitendinosus and gluteus maximus | 33% |
| Kotek 2024[32] | Czech Republic | Retrospective cohort study | 206 | Median (IQR) age 67 (59–73); 65.5% male | Yes, NCRT | Elective only; robotic, laparoscopic, open | SMD | L3 | Continuous variable | Psoas muscle | N/A |
| Pekarova 2021 [33] | Czech Republic | Retrospective cohort study | 112 | Mean age ± SD: 68.3 ± 10.4; male 66.0%, female 34% | Yes, 36.2% of rectal cancer cases underwent neoadjuvant chemoradiotherapy | Laparascopic surgery or open | SMD | L3 | No cut-off specified; continuous variable | Psoas muscle only | Not stated |
| Benedek 2021[34] | Romania | Prospective cohort study | 51 | Median age 65 years (interquartile range (IQR), 56–71); male, 62% | Unknown | Unknown | SMD | L3 | Continuous variable | Psoas muscle | Not stated |
| Herrod 2019[35] | UK | Retrospective cohort study | 169 | Mean age ± SD: 68 ± 11 years; Male 53.8% | Yes | Unknown | SMD | L3 | Whole cohort, SMD ≤ 44.5 HU; anastomosis group, SMD ≤ 43.5 HU | Psoas muscle only | 30.20% |
| Gao 2025 [36] | China | Retrospective cohort study | 317 | Median age (IQR) 66 (58–72) years; 64.7% male | Not specified | Elective only; laparoscopic or open | IMAC = mean CT value of ROI of multifidus muscle (HU)/mean CT value of ROI of subcutaneous fat (HU) | L3 | Sex-specific lowest 25th percentile (34.76 HU for males and 31.82 HU for females) | Psoas muscle | 24.9 |
| Parnasa 2025[37] | Israel | Retrospective cohort study | 843 | 55.0% male | Unknown | Laparoscopic and open, elective and emergency included | SMD | L3 | Continuous variable | Psoas muscle | N/A |
| Okugawa 2018[38] | Japan | Retrospective cohort study | 308 | Age > 67: 48.4%; male 59.4% | Yes, adjuvant chemotherapy | Open and laparoscopic | IMAC = mean CT value of ROI of multifidus muscle (HU)/mean CT value of ROI of subcutaneous fat (HU) | Superior aspect of L4 | Sex-specific median value (male: IMAC: − 0.36; female: IMAC: − 0.24) | Multifidus muscle | 49.70% |
| Kusunoki 2021[39] | Japan | Retrospective cohort study | 471 | Median age: 68 years (range, 27–94 years); 59.7% male | Yes, Adjuvant chemotherapy | Unknown | IMAC = mean CT value of the ROI of the multifidus muscle (HU)/mean CT value of the ROI of the subcutaneous fat (HU); mIMAC = mean CT value of the ROI of the multifidus muscle (HU) − mean CT value of the ROI of the subcutaneous fat (HU) | L4 | Male: IMAC: − 0.368 and mIMAC: 143.13; female: IMAC: − 0.433 and mIMAC: 133.06 | Multifidus muscle | IMAC, 61.8%; mIMAC, 48.0% |
| Margadant 2016[40] | Netherlands | Retrospective cohort study | 373 | Median age: 78 years (IQR 75–82 years); male 48.5% | Yes, adjuvant and NCRT | Laparoscopic or open | HUAC (measured as: ([right average HU*right psoas area]/[TPA] + [left average HU*left psoas area]/[TPA])/2) | L3 | Male: ≤ 22.0 HU/mm2; female: ≤ 23.5 HU/mm2; as well as continuous variable | Psoas muscle only | 24.70% |
| Souwer 2020[41] | Netherlands | Retrospective cohort study | 174 | Mean age ± SD: 78.0 years ± 5.1; 51.1% Male | Yes, Adjuvant chemotherapy and NCRT | All elective; laparoscopic 65.5% | SMD | L3 | Martin’s definition | TAMA | 87.40% |
| Chen 2022[42] | China | Retrospective cohort study | 921 | Median age: 73 years (IQR 10); male 60.8% | Unknown | Laparoscopic or open; no emergency surgeries | SMD | L3 | Male, 38.5 HU; female, 28.6 HU | TAMA | 68.70% |
| Boer 2016[43] | USA | Retrospective cohort study | 1630 | Mean age ± SD: 64.0 ± 11.3 years; male 44.4% | Unknown | Unknown | SMD | L3, L4 superior, L4 inferior | Xiao’s definition | TAMA | Not stated |
| Berkel 2019[44] | Netherlands | Retrospective cohort study | 99 LARC | Median age: 66 (range 40–81); 53.5% males | Yes, NCRT | Open and laparoscopic | SMD | L3 | Continuous variable | TAMA | Not stated |
| Aro 2020[45] | Finland | Retrospective cohort study | 348 | Mean age ± SD: 68 ± 11.5 years; 182 men (52%) and 166 women (48%) | Yes, adjuvant and/or neoadjuvant CRT | Emergency and elective; open and laparoscopic | SMD | L3 | Martin’s definition | TAMA | 31.20% |
| McGovern 2023[46] | Scotland | Retrospective cohort study | 1002 | Age ≥ 65: 65.6%; male 55.3% | Yes, NCRT | Unknown | SMD | L3 | Martin’s definition | TAMA | Not stated |
| Van der Krof 2018 [47] | Netherlands | Prospective cohort study | 63 | Mean age ± SD: 69 ± 10.5 years; male 61.9% | Yes, neoadjuvant therapy | Elective surgery only; laparoscopic and open | SMD | L3 | Median value as cut-off (low: < 34.1 HU; high: ≥ 34.1 HU) | TAMA | 50% |
| Almasaudi 2019[48] | Scotland | Retrospective cohort study | 741 | Age ≥ 65: 64.2%; 55.3% male | Yes, NCRT | Laparoscopic or open | SMD | L3 | Martin’s definition | TAMA | 62.50% |
| Xiao 2020[49] | US | Retrospective cohort study | 1630 | Mean age ± SD: 64.0 ± 11.3 years, 44.4% were male | Unknown | Laparoscopic and endoscopic polpectomy only | SMD | L3 | Xiao’s definition | TAMA | 30.40% |
| Malietzis 2016[50] | UK | Prospective cohort study | 805 | Median age of 69 (61–77) years; Male 58.6% | Yes, NCRT and CRT | Laparoscopic or open | SMD | L3 | Martin’s definition | TAMA | 77.60% |
| Martin 2018[51] | UK and Canada | Retrospective cohort study | 1139 | Mean age ± SD: 66.6 ± 11.9 years; male 60.5% | Unknown | Laparoscopic or open; no emergency | SMD | L3 | Male: < 50 y: < 42.0; 50–59 y: < 37.6; 60–69: < 32.9; 70–79: < 29.7; ≥ 80: < 28.1; female: < 50 y: < 39.6; 50–59 y: < 36.0; 60–69: < 31.4; 70–79: < 27.8; ≥ 80: < 24.8 | TAMA | 50% |
| vanRees 2021 [52] | Netherlands | Retrospective cohort study | 227 | Age ≥ 70: 32.2%; male 40.5% | Yes, neoadjuvant chemo- and/or radiotherapy therapy for most patients | Total (111) or posterior (116) pelvic exenteration surgery | SMD | L3 | Martin’s definition | TAMA | 57.20% |
| Hopkins 2019[53] | Canada | Retrospective cohort study | 968 | Mean age ± SD: 65.8 ± 11.8 years; 589 men (61%) and 379 women (39%) | Yes, Adjuvant CRT | Unknown | SMD | L3 | Martin’s definition | TAMA | 61.10% |
| Sueda 2018[54] | Japan | Retrospective cohort study | 211 | Age ≥ 65: 50.7%; 134 men (63.5%) | Elective surgery only; laparoscopic and open | SMD | L3 | Martin’s definition | TAMA | 52.10% | |
| McSorley 2018[55] | Scotland | Retrospective cohort study | 322 | Age ≥ 65: 67%; 174 men (54%) and 148 women (46%) | Unknown | Elective surgery | SMD | L3 | Martin’s definition | TAMA | 57.80% |
| vanBaar 2018 [56] | Netherlands | Retrospective cohort study | 1681 | Mean age ± SD: 67.7 ± 10.3 years; Men 59.4% | Unknown | Unknown | SMD | L3 | Men: BMI < 25 kg/m2: 36.4 HU, BMI ≥ 25 kg/m2: 31.6 HU; Women: BMI < 25 kg/m2: 31.1 HU, BMI ≥ 25 kg/m2: 29.3 HU | TAMA | 38.50% |
| Dolan 2019[57] | Scotland | Retrospective cohort study | 650 | Age > 65: 64.0%; male 54.5% | Unknown | Elective surgery only | SMD | L3 | Xiao’s definition | TAMA | 52.50% |
| Aro 2022[58] | Finland | Retrospective cohort study | 222 | Age ≥ 70: 57.2%; male 52.7% | No NCRT | Unknown | SMD | L3 | Martin’s definition | TAMA | 30.20% |
| Koh 2022[59] | South Korea | Retrospective cohort study | 1015 | Age ≥ 70: 30.8%; Male 59.0% | No NCRT | Unknown | SMD | L3 | Martin’s definition | TAMA | Not stated |
| Cho 2024[60] | South Korea | Retrospective cohort study | 1053 | Mean age ± SD: 62.8 ± 11.8 years; male [59.1%] | Yes, adjuvant chemotherapy | Unknown | SMD | L3 | Martin’s definition | TAMA | 29.40% |
| Kim 2023[61] | South Korea | Retrospective cohort study | 906 | Median age: 64 (IQR 55–72) years: 59.7% male | Yes, adjuvant chemotherapy | Unknown | SMD | L3 | Martin’s definition | TAMA | Not stated |
| Golder 2022[62] | Scotland | Retrospective cohort study | 1146 | Age > 65: 36.8%; Male 51.4% | Yes, adjuvant chemotherapy | Either elective or emergency | SMD | L3 | Xiao’s definition | TAMA | 62.00% |
| Zhou 2024[63] | China | Retrospective cohort study | 327 | Mean ± SD age 60.9 ± 10.6 years, 62.7% female | NCRT excluded | Open and laparoscopic | SMD | Unspecified | Median value of sample’s data distribution (unspecified value) | Unspecified | 49% |
| Renman 2023 [64] | Sweden | Retrospective cohort study | 519 | Median age: 66.5 years (range 41.5–85.6); male 50.7% | Unknown | Unknown | SMD | L3 | Lowest sex-specific tertile of SMD (male, 38.5 HU; female, 36.1 HU) | TAMA | 31.40% |
| Yokoi 2022[65] | Japan | Retrospective cohort study | 341 | Age ≥ 70: 44.9%; 58.7% men | Yes, NCRT and CRT | Unknown | SMD | L3 | Male: < 35.0 HU; female: < 21.7 HU | TAMA | Not stated |
| Wei 2024[66] | Australia | Retrospective cohort study | 214 | Mean age ± SD: 62.4 ± 12.7 years; male 70.6% | Yes, NCRT | Open and laparoscopic | IMAT volume, mean IMAT density, SMD | L1–L5 | Continuous variable | TAMA (for SMD) | N/A |
IMFAR, intramuscular fat area ratio, measured as IMFA/TMA, intramuscular fat area/total muscle area; HUAC, measured as ([right average HU*right psoas area]/[total psoas area] + [left average HU*left psoas area]/[total psoas area])/2); IMAC, intramuscular adipose content, measured as mean CT value of the ROI of the multifidus muscle (HU)/mean CT value of the ROI of the subcutaneous fat (HU); mIMAC, modified intramuscular adipose content, measured as mean CT value of the ROI of the multifidus muscle (HU) − mean CT value of the ROI of the subcutaneous fat (HU); IMFA, intermuscular fat area, measured as fat contained in the spaces between the muscles of the abdominal wall that does not belong to the VFA or SFA compartments. Martin’s definition: body mass index (BMI) < 25 kg/m2: HU < 41; BMI ≥ 25 kg/m2: HU < 33. Xiao’s definition: males, < 35.5 HU; females, < 32.5 HU. SD standard deviation, IQR interquartile range, NCRT neoadjuvant chemotherapy, SMD skeletal muscle density, HU Hounsfield units, TAMA total abdominal muscle area
Measurement and definition of myosteatosis
Myosteatosis was evaluated on preoperative CT scans up to 3 months before surgery. The use of intravenous contrast for these CT scans was specified in 20 of the 54 studies included [13–32].
The most common method for detecting myosteatosis on CT scans was the use of skeletal muscle radiodensity (SMD), which measures the mean radiodensity of tissue areas of −29 to 150 HU in attenuation (Table 1). The most common area examined was the total abdominal muscular area at the level of L3 or L4 (37 of 54 studies). The majority of studies determined the cut-off for myosteatosis by Martin’s definition (< 33HU in men and women of BMI ≥ 25 and < 41 for men and women with BMI < 25) (20 out of 37) and Xiao’s definition (men, < 35.5HU; women, < 32.5HU) (four out of 37) [67, 68]. Figure 2 shows the schematic representation of types of fatty infiltration into muscle (Fig. 2a) and schematic representation of CT-based measurements of myosteatosis at the level of L3 (Fig. 2b).
Fig. 2.
Evaluation of radiologically defined myosteatosis. a Schematic representation of types of fatty infiltration into muscle including intermuscular or extrafascial adipose (D) which is external to the muscle and its fascia (A); perimuscular or subfascial (E) which exists within a muscle external to individual muscle fascicles (B); intramuscular adipose (G) which exists within fascicles adjacent to myocytes (C); and intramyocellular lipid droplets (F) which exist within individual myocytes (C). b Schematic representation of CT-based measurements of myosteatosis at the level of L3 including in panel A, where total abdominal musculature is highlighted in blue and represents the total area from which the average radiological attenuation is measured to generate skeletal muscle density (SMD) measurements. Areas of intermuscular adipose infiltration are highlighted in yellow; the area of these regions may be utilised for calculations of intermuscular fat infiltration or IMAT
Ten studies measured myosteatosis based on examination of the psoas muscles. Seven out of the ten studies evaluated SMD of psoas muscles [20, 25, 32–37], while the other three studies utilised HUAC as the index measurement of myosteatosis. For the studies utilising SMD, the majority of studies treating the variable as a continuous variable in their analysis without any specification of a cut-off value. HUAC was measured as:
All three of the studies utilising HUAC had different sex-specific cut-off values for myosteatosis.
One study by Ferreira et al. utilised the mean SMD of both thighs at the level of the lesser trochanter of the femur as the measure for myosteatosis.
Other studies utilised segmented inter-/intramuscular adipose tissue area (IMAT), with tissue areas of radiological attenuation between −190 and −30 HU defined as IMAT. However, among these studies, the cut-off volume for myosteatosis was heterogenous with most studies opting to utilise analyses of variance.
Variants of IMAT such as inter-/intramuscular fat area ratio (IMFAR) and inter-/intramuscular adipose tissue content were also used as index measurements for myosteatosis. Intramuscular adipose tissue content (IMAC) was described by Okugawa and Kusunoki as a measurement involving the attenuation value (in Hounsfield Units) of the multifidus muscle, divided by the mean attenuation of adipose tissue, adapted from Kitajima’s measurements of fat deposition [38, 39, 69]. Giani et al.’s two studies in Italy measured myosteatosis using IMFAR, defined as intramuscular fat area/total muscle area [28, 29].
Wei et al.’s 2024 study was the only study out of the 54 to utilise SMD measurements over multiple levels (L1-L5) and measured IMAT volume and density rather than just cross-sectional area across L1-L5 [66]. However, cut-off values for IMAT volume and density to diagnose myosteatosis were not proposed. Furthermore, Lee’s 2023 and Wei’s 2024 studies were the only two studies to use fully automated artificial intelligence body composition algorithms to segment and quantify different body composition parameters, including IMAT area and volume and SM area and density [13, 68].
Postoperative complications
Overall complications
Ten studies investigated the association between myosteatosis and overall postoperative complications in colorectal cancer, with only four of these studies finding a significant correlation [16, 18, 24, 36, 41, 42, 45–48]. Two out of the four studies (Van Vugt 2018 and Gao 2025) were deemed to be good quality based on the NOS [18, 36]. Van Vugt’s prospective cohort study utilised SMD TAMA as the measurement for myosteatosis, finding 51.7% of the low SMD group developed postoperative complications compared to 38.5% for those with normal SMD (p < 0.001) [18]. Gao utilised HUAC measurement based on psoas muscles and demonstrated a hazard ratio (HR) of 1.8 (95% CI 1.0–3.3, p = 0.039) [36]. In contrast, two other studies that were considered good quality based on the NOS found no significant association [24, 45].
Four studies investigated the association between myosteatosis and overall postoperative complications in colon cancer only, with half of the studies finding a significant correlation [21, 26, 43, 49]. Boer et al. utilised SMD of TAMA (Xiao’s definition) and Tankel utilised HUAC [26, 43]. However, both studies were deemed to be poor quality based on the NOS; the other two studies on colon cancer, deemed good quality, found no significant association when using SMD of TAMA (Martin and Xiao’s definitions) [21, 49].
Overall, there was a paucity of studies investigating myosteatosis and overall postoperative complications in rectal cancer patients. Out of the three studies investigating the association between myosteatosis and overall postoperative complications in rectal cancer, only one study found a significant association, utilising SMD of TAMA (no cut off; continuous variable); however, this achieved a poor quality rating on NOS [17, 44, 66].
Severity of complications
Fourteen studies investigated the association between myosteatosis and severe postoperative complications (defined as Clavien-Dindo 3) in colorectal cancer [16, 18, 20, 23, 34–37, 40–42, 45, 50, 51]. Five of these studies were assessed to be of good quality, including three which found a significant correlation [18, 23, 35, 36, 40]. Two of the studies (Van Vugt 2018 and Looijaard 2020) utilised SMD based on TAMA, while Gao’ s study utilised psoas HUAC [18, 23, 36]. HRs of these three studies ranged from 1.87 (95% CI 1.01–3.46, p = 0.045) to 3.8 (95% CI 1.5–9.6, p = 0.005).
Out of the three studies investigating the association between myosteatosis and severe postoperative complications in colon cancer only, all three found a significant association [26, 33, 49]. Xiao used SMD of TAMA, while Tankel utilised HUAC of psoas muscles, while Pekarova used SMD of psoas muscles. However, only one study (Xiao 2020) was deemed to be good quality on NOS. Xiao’s study found a HR of 2.41 (95% CI 1.44–4.04, p < 0.05) [49].
Out of the five studies investigating the association between myosteatosis and severe postoperative complications in rectal cancer only, three found a significant association [25, 32, 33, 44, 52]. However, all three were deemed to be poor quality according to NOS.
Anastomotic leak (AL)
Eight studies investigated the association between myosteatosis and anastomotic leak in colorectal cancer, with only one study found to be of good quality [19, 20, 35, 40, 41, 45, 48, 50]; Aro et al. utilised the SMD of TAMA (Martin’s definition) and found that there was no significant association between myosteatosis and the risk of anastomotic leak [44]. Of the eight studies that found a significant correlation, two studies measured the SMD of psoas muscles, one utilised the SMD of TAMA and one used the HUAC of psoas muscles [19, 20, 35, 40]. None was deemed good quality according to NOS.
Overall, there was a paucity of studies investigating myosteatosis and AL in colon or rectal cancer only. Out of the two studies investigating the association between myosteatosis and anastomotic leak in colon cancer only, both found a significant association, while none of the three studies investigating the association between myosteatosis and anastomotic leak in rectal cancer found a significant association [28, 32, 33, 49].
Length of stay (LOS)
Ten studies investigated the association between myosteatosis and length of stay (LoS) in colorectal cancer, with four good quality studies identified [18–20, 23, 37, 40, 42, 45, 50, 51]. Of these, Van Vugt et al. found a correlation between myosteatosis, measured by SMD of TAMA (Martin’s definition), and longer LoS (median LoS 8 days, IQR 6–14, compared with 7 days IQR 5–10, p < 0.001). Other good quality studies did not demonstrate a significant correlation between myosteatosis and LoS [23, 37, 45].
Overall, there was a paucity of studies investigating myosteatosis and LoS in colon or rectal cancer only.
Among two studies focussing on colon cancer, Xiao et al.’s research was deemed to be of good quality and found an increased risk of prolonged LoS in patients with myosteatosis (HR 1.39, 95% CI 1.05–1.84) [49]. Only one study investigated rectal cancer populations only, finding higher SM density of TAMA was an important independent prognostic factor for better LoS in rectal cancer patients (HR 1.58, 95% CI 1.03–2.43, p = 0.036) [66]. Results from the studies investigating the association between myosteatosis and postoperative complications are presented in Table 2.
Table 2.
Association between myosteatosis and post-operative complications in non-metastatic and metastatic CRC
| Author | Overall | Severity (i.e. Clavien-Dindo (CD) =/> 3) | Anastomotic leak | Length of stay (LOS) |
|---|---|---|---|---|
| Colorectal cancer | ||||
| VanVugt (2018) [18] | Myosteatosis vs non-myosteatosis: 51.7% vs 38.5%, p < 0.001 | HR 1.87, 95% CI 1.01–3.46, p = 0.045 | - | Myosteatosis vs non-myosteatosis: median [IQR], days 8 [6 - 14] vs 7 [5 - 10], p < 0.001 |
| Kusunoki (2021) [39] | - | - | - | - |
| Aro (2020) [45] | No significant association | No significant association | No significant association | No significant association |
| Souwer (2020) [41] | Myosteatosis vs non-myosteatosis: 49% vs 28%, p = 0.046 | No significant association | No significant association | - |
| McGovern (2023) [46] | No significant association | - | - | - |
| Bimurzayeva (2024) [24] | No significant association | - | - | - |
| Looijaard (2020) [23] | - | Non-myosteatosis compared to myosteatosis: HR 0.684, 95% CI 0.486–0.962, p < 0.05 | - | No significant association |
| Blackwell (2023) [20] | - | No significant association | HR 3.13, 95% CI 1.05–9.33; p = 0.04 | No significant association |
| Van der Kroft (2018) [47] | No significant association | - | - | - |
| Benedek (2021) [34] | - | No significant association | - | - |
| Kemper (2023) [19] | - | - | Every 10HU increase associated with decreased odds of 47%, 95% CI 7.7%–103%, p = 0.017 | HR for the event hospital discharge for non-myosteatosis compared to myosteatosis group: HR 1.25, 95% CI: 1.05–1.48, p = 0.011 |
| Chen (2022) [42] | HR 1.478, 95% CI 1.040–2.099, p = 0.029 | No significant association | - | Myosteatosis vs non-myosteatosis: median [IQR], days 12 [7] vs 11 [6], p < 0.001 |
| Almasaudi (2019) [48] | Male, no significant association; female, no significant association | - | Male: No significant association; Female: No significant association | - |
| Margadant (2016) [40] | - | HR 1.84, 95% CI 1.11–3.06, p = 0.019 | Myosteatosis vs non-myosteatosis: 23.3% vs 11.7%, p = 0.016 | Myosteatosis vs non-myosteatosis: median (min–max), days 13 (2–126) vs 10 (1–130), p = 0.025 |
| Malietzis (2016) [50] | - | No significant association | No significant association | Myosteatosis vs non-myosteatosis: median [IQR], days 7 [5 - 11] vs 6 [4 - 9] days respectively, p = 0.034 |
| Cuijpers (2022) [16] | No significant association | No significant association | - | - |
| Martin (2018) [51] | - | No significant association | - | No significant association |
| Herrod (2019) [35] | - | HR 6.33, 95% CI 1.6–24.24, p = 0.007 | HR 14.37, 95% CI 1.3–150.0, p = 0.026 | - |
| Gao (2025) [36] | HR 1.8, 95% CI 1.0–3.3, p = 0.039 | HR 3.8, 95%CI 1.5–9.6, p = 0.005 | - | - |
| Parnasa (2024) [37] | - | No significant association | - | No significant association |
| Colon cancer | ||||
| Schaffler-Schaden (2020) [21] | No significant association | - | - | - |
| Boer (2016) [43] |
L3 level: HR 0.912, 95% CI 0.863–0.964, p = 0.001 L4 (superior) level: HR 0.918, 95% CI 0.871–0.967, p = 0.001; L4 (inferior) level: 0.922, 95% CI 0.875–0.972, p = 0.003 |
- | - | - |
| Xiao (2020) [49] | No significant association | HR 2.41, 95% CI 1.44–4.04, p < 0.05 | HR 1.67, 95% CI 1.02–2.74, p < 0.05 | LOS ≥ 7 days: HR 1.39, 95% CI 1.05–1.84, p < 0.05 |
| Tankel (2020) [26] | HR 1.68, 95% CI 0.60–1.16, p = 0.009 | Myosteatosis significantly associated with CD =/> 3 (p = 0.015) | - | No significant association |
| Pekarova (2021) [33] | - | PD was significantly lower in the Cl-Di III-V cohort compared to the Cl-Di 0-II cohort (Mean ± SD: 42.67 ± 6.52 vs. 40.11 ± 7.57 HU, p = 0.002) | PD was significantly lower in patients with anastomotic leakage compared to those without leak (Mean ± SD: 31.40 ± 7.50 vs. 42.73 ± 6.37, p = 0.034) | - |
| Rectal cancer | ||||
| Giani (2020) [28] | - | - | No significant association | - |
| Berkel (2019) [44] | Non-myosteatosis compared to myosteatosis: HR 0.91; 95% CI 0.85–0.97, p = 0.003 | Non-myosteatosis compared to myosteatosis: HR 0.89, 95% CI 0.83–0.96; p = 0.002 | - | - |
| Xiao (2023) [25] | - | Non-myosteatosis compared to myosteatosis: HR 0.94, 95% CI 0.88–0.99, p = 0.04 | - | - |
| vanRees (2021) | - | No significant association | - | - |
| Pacquelet (2022) [17] | No significant association | - | - | - |
| Pekarova (2021) [33] | - | PD was significantly lower in the Cl-Di III-V cohort compared to the Cl-Di 0-II cohort (Mean ± SD: 44.08 ± 5.86 vs 43.03 ± 5.70 HU, p = 0.016) | No significant association | - |
| Kotek (2024) [32] | - | No significant association | No significant association | - |
| Wei (2024) [66] | No significant association | - | - | SMD: HR 1.58, 95% CI 1.03–2.43, p = 0.036 |
HR hazard ratio, CI confidence interval, SD standard deviation, IQR interquartile range, HU Hounsfield unit
Survival
Overall survival
Twenty-three studies investigated the association between myosteatosis and overall survival in colorectal cancer [14, 18, 19, 23, 24, 30, 31, 38, 41, 42, 45, 50, 53–61, 63, 64]. Twenty out of the twenty-three studies utilised SMD of TAMA to measure myosteatosis. Fifteen of these studies found a significant correlation, and fourteen of these studies measured SMD of TAMA, with the majority using Martin’s criteria as the cut-off value [16, 28, 39, 43, 48, 51–53, 56–58]. One study (Ferreira, 2024) measured myosteatosis using SMD of the bilateral thighs. However, no cut-off value was specified, as the value was treated as a continuous variable. Cho et al.’s study found a significant association between myosteatosis and OS in the group 51–74 years (non-myosteatosis compared to myosteatosis group HR 0.63 (0.41−0.96), p = 0.033). However, no significant association was found in the age group ≥ 75 years. Only five out of these fifteen studies were deemed to be of good quality according to NOS. The hazard ratios ranged from 1.54 (95% CI 1.19–1.98, p = 0.001) in Hopkins et al.’s study, which utilised SMD of TAMA (Martin’s definition), to 2.43 (95% CI 1.327–4.449, p = 0.004) in Birmurzayeva’s study, which utilised SMD of TAMA and sex-specific cut-offs [24, 53].
Four out of the five studies investigating the association between myosteatosis and overall survival in colon cancer only found a significant correlation (HRs ranging from 1.44, 95% CI 1.12–1.85, p < 0.05; to 1.90, 95% CI 1.84–3.04, p = 0.008) [15, 22, 27, 49, 62]. All four studies utilised SMD of TAMA to quantify myosteatosis, with different cut-off values utilised by each study. Three out of these four studies were deemed to be good quality according to NOS.
One out of the three studies investigating the association between myosteatosis and overall survival in rectal cancer only found significant associations. Interestingly, Wei’s 2024 study found that although higher SMD was an important independent prognostic factor for better OS (HR 0.24, 95% CI 0.06–0.86, p = 0.029), higher IMAT volume and density, which represent increased myosteatosis, were also associated with improved OS (IMAT volume: HR 0.13, 95% CI 0.03–0.59, p = 0.008; IMAT density: HR 0.26, 95% CI 0.10–0.68, p = 0.006) [66].
Cancer-specific survival
Nine studies investigated the association between myosteatosis and cancer-specific survival (CSS) in colorectal cancer, with only three of these studies finding a significant correlation [18, 30, 38, 53–56, 58, 64]. All three of the studies quantified SMD of TAMA and defined myosteatosis using Martin’s criteria. Only one of the three studies was deemed good quality (HR, 1.42; 95% CI, 1.04–1.93, p = 0.026) [53].
No studies investigated CSS in colon or rectal cancer only.
Disease-free survival
Fourteen studies investigated the association between myosteatosis and disease-free survival in colorectal cancer [13, 18, 24, 30, 38, 45, 50, 53, 54, 56, 58, 61, 63, 65]. Six studies in total found a significant correlation between myosteatosis and DFS; all utilised SMD of TAMA to measure myosteatosis, but the cut-off value for myosteatosis varied among the studies. Only two out of these six studies were deemed to be of good quality according to NOS; the other four did not find a significant correlation.
Both studies investigating the association between myosteatosis and disease-free survival in colon cancer found a significant correlation, using SMD of TAMA and different sex-specific cut-offs [15, 22]. One out of the three studies investigating the association between myosteatosis and overall survival in rectal cancer found significant associations. Wei’s 2024 study found that higher SMD was an important independent prognostic factor for better DFS (HR 0.45, 95% CI 0.2–0.99, p = 0.048). However, no significant association was found between IMAT volume and density and DFS. However, these studies were limited by their NOS rating. Results from the studies investigating the association between myosteatosis and survival outcomes in non-metastatic CRC are presented in Table 3.
Table 3.
Association between myosteatosis and survival outcomes in non-metastatic CRC
| Author | Overall survival | Cancer-specific survival | Disease-free/recurrence-free survival |
|---|---|---|---|
| Colorectal cancer | |||
| Carcamo (2021) [30] | No significant association | No significant association | No significant association |
| VanVugt (2018) [18] | No significant association | No significant association | No significant association |
| Hopkins (2019) [53] | HR 1.54, 95% CI 1.19–1.98, p = 0.001 | HR, 1.42; 95% CI 1.04–1.93, p = 0.026 | No significant association |
| Aro (2020) [45] | HR 1.6, 95% CI 1.04 to 2.56, p = 0.034 | - | No significant association |
| Sueda (2018) [54] | HR 2.94, 95% CI 1.32–7.17, p < 0.01 | HR 3.37, 95% CI 1.38–9.43, p < 0.01 | HR 2.73, 95% CI 1.41–5.53, p < 0.01 |
| McSorley (2018) [55] | HR 2.29, 95% CI 1.38–3.81, p = 0.001 | HR 2.11, 95% CI 1.14–3.92, p = 0.017 | - |
| Souwer (2020) [41] | No significant association | - | - |
| vanBaar (2018) | HR 1.91, 95% CI 1.53–2.38 p < 0.05 | No significant association | HR 1.68, 95% CI 1.14–2.47, p < 0.05 |
| Renman (2023) [64] | No significant association | No significant association | - |
| Bimurzayeva (2024) [24] | HR 2.430, 95% CI 1.327–4.449, p = 0.004 | - | HR 2.049, 95% CI 1.129–3.718, p = 0.018 |
| Looijaard (2020) [23] | No significant association | - | - |
| Dolan (2019) [57] | HR 1.42, 95% CI 0.98–2.05, p = 0.061 | - | - |
| Aro (2022) [45] | HR 1.81, 95% CI 1.00–3.26, p = 0.048 | No significant association | No significant association |
| Koh (2022) [59] | Non-myosteatosis compared to myosteatosis group: HR 0.648; 95% CI 0.486–0.865; p = 0.003 | - | |
| Kemper (2023) [19] | + 10 HU increase is associated with lower HR of death 0.63, 0.49–0.81, p < 0.001 | - | - |
| Chen (2022) [42] | HR 1.489, 95% CI 1.147–1.932, p = 0.003 | - | - |
| Lee (2023) [13] | - | - | Non-myosteatosis compared to myosteatosis group: HR 0.543, 0.392–0.753, p < 0.001 |
| Okugawa (2018) [38] | No significant association | No significant association | No significant association |
| Malietzis (2016) [50] | No significant association | - | No significant association |
| Cho (2024) [60] |
Age group 51–74: non-myosteatosis compared to myosteatosis group HR 0.63 (0.41 − 0.96), p = 0.033 Age ≥ 75: no significant association |
- | - |
| Kim (2023) [61] | HR 1.90, 95% CI 1.84–3.04, p = 0.008 | - | HR 1.89, 95% CI 1.25–2.86, p = 0.003 |
| Yokoi (2022) [65] | - | - | HR 2.49, 95% CI 1.21–4.95, p = 0.01 |
| Lee (2023) [13] | HR 1.55; 95% CI, 1.32–1.82, p < 0.05 | - | - |
| Ferreira (2024) [31] | Stage I–III: HR adjusted 2.78, 95% CI 1.26–6.15, p = 0.012 | - | - |
| Zhou (2024) [63] | No significant association | - | No significant association |
| Colon cancer | |||
| Chung (2020) [27] | No significant association | - | - |
| Xiao (2020) [25] | HR 1.44, 95% CI 1.12–1.85, p < 0.05 | - | - |
| Kim (2023) [15] | HR 1.90, 95% CI 1.84–3.04, p = 0.008 | - | HR 1.89, 95% CI 1.25–1.86, p = 0.003 |
| Golder (2022) [62] |
Stage II: (3-yr OS: myosteatosis 85% vs NM 96%, p < 0.001) Stage III: 3-yr OS myosteatosis 75% vs NM 76%, p = 0.034) |
- | - |
| Pozzuto (2021) [22] |
SMD: non-myosteatosis compared to myosteatosis group HR 0.91, 95% CI 0.87–0.95, p < 0.001 IMAT: HR 1.06, 95% CI 1.03–1.09, p < 0.001 |
- | SMD: Non-myosteatosis group compared to myosteatosis group HR 0.95, 95% CI 0.91–0.98, p = 0.003 IMAT: HR 1.03, 95% CI 1.01–1.06, p = 0.011 |
| Rectal cancer | |||
| vanRees (2021) | No significant association | - | - |
| Pozzuto (2021) [22] | No significant association | - | No significant association |
| Giani (2022) [28] | - | - | No significant association |
| Wei (2024) [66] | High SMD: HR 0.24, 95% CI 0.06–0.86, p = 0.029; high IMAT volume: HR 0.13, 95% CI 0.03–0.59, p = 0.008; high IMAT density: HR 0.26, 95% CI 0.10–0.68, p = 0.006 | - | High SMD: HR 0.45, 95% CI 0.2–0.99, p = 0.048 |
HR hazard ratio, CI confidence interval, HU Hounsfield unit
GRADE summary of evidence certainty
The quality of included studies was assessed using the Newcastle–Ottawa Scale (NOS) for cohort studies [12]. Only 16 of 54 studies were found to be of “good” quality, as assessed by the Newcastle Ottawa rating scale and Agency for Healthcare Research and Quality (AHRQ) standards (Table 4). Many studies were deemed to be at high risk of publication bias due to limited adjustment for potential confounders, insufficient follow-up periods for assessment of survival and a failure to report the number of participants lost to follow-up or the reasons for their loss. Overall, the certainty of evidence regarding the prognostic impact of myosteatosis in colorectal cancer is low to moderate. The evidence supporting an association between myosteatosis and overall survival (OS) is moderate-certainty, downgraded primarily for risk of bias due to the predominance of retrospective designs, incomplete adjustment for key confounders and incomplete information on follow-up data. Findings for colon cancer are more consistent and therefore of moderate certainty, whereas evidence for rectal cancer is inconsistent and of low certainty.
Table 4.
Assessment of study quality based on Newcastle–Ottawa scale
| Study | Selection | Comparability | Outcome | Overall quality |
|---|---|---|---|---|
| Giani (2020) [28] | 4 | 0 | 0 | Poor |
| Carcamo (2021) [30] | 4 | 1 | 2 | Good |
| VanVugt (2018) [18] | 4 | 2 | 3 | Good |
| Chung (2020) [27] | 4 | 1 | 0 | Poor |
| Tankel (2020) [26] | 4 | 1 | 1 | Poor |
| Hopkins (2019) [53] | 4 | 2 | 2 | Good |
| Kusunoki (2021) [39] | 4 | 2 | 1 | Poor |
| Aro (2020) [45] | 4 | 1 | 2 | Good |
| Sueda (2018) [54] | 4 | 2 | 1 | Poor |
| Berkel (2019) [44] | 4 | 2 | 1 | Poor |
| McSorley (2018) [55] | 3 | 1 | 1 | Poor |
| Xiao (2023) [49] | 4 | 1 | 1 | Poor |
| Souwer (2020) [41] | 4 | 2 | 1 | Poor |
| vanBaar (2018) | 4 | 2 | 1 | Poor |
| McGovern (2023) [46] | 4 | 0 | 1 | Poor |
| Lee (2023) [13] | 4 | 1 | 2 | Good |
| Renman (2023) [64] | 4 | 1 | 2 | Good |
| Golder (2022) [62] | 4 | 1 | 2 | Good |
| Bimurzayeva (2024) [24] | 3 | 1 | 2 | Good |
| Looijaard (2020) [23] | 4 | 1 | 2 | Good |
| Pozzuto (2021) [22] | 4 | 1 | 1 | Poor |
| Schaffler-Schaden (2020) [21] | 3 | 1 | 2 | Good |
| Pekarova (2021) [33] | 3 | 0 | 0 | Poor |
| Blackwell (2023) [20] | 4 | 1 | 1 | Poor |
| Boer (2016) [43] | 4 | 2 | 1 | Poor |
| vanderKroft (2018) | 3 | 2 | 1 | Poor |
| Dolan (2019) [57] | 3 | 0 | 1 | Poor |
| Aro (2022) [45] | 4 | 1 | 2 | Good |
| Koh (2022) [59] | 3 | 0 | 2 | Poor |
| Benedek (2021) [34] | 3 | 0 | 1 | Poor |
| Kemper (2023) [19] | 4 | 2 | 1 | Poor |
| Chen (2022) [42] | 4 | 0 | 1 | Poor |
| vanRees (2021) | 3 | 1 | 1 | Poor |
| Lee (2023) [13] | 3 | 1 | 0 | Poor |
| Almasaudi (2019) [48] | 3 | 1 | 0 | Poor |
| Margadant (2016) [40] | 4 | 1 | 1 | Poor |
| Okugawa (2018) [38] | 3 | 1 | 1 | Poor |
| Xiao (2020) [49] | 4 | 2 | 2 | Good |
| Kim (2023) [61] | 3 | 1 | 2 | Good |
| Malietzis (2016) [50] | 4 | 1 | 1 | Poor |
| Cuijpers (2022) [16] | 2 | 1 | 1 | Poor |
| Cho (2024) [60] | 3 | 1 | 0 | Poor |
| Martin (2018) [51] | 4 | 1 | 1 | Poor |
| Herrod (2019) [35] | 4 | 1 | 1 | Poor |
| Pacquelet (2022) [17] | 4 | 1 | 1 | Poor |
| Kim (2023) [15] | 4 | 1 | 1 | Poor |
| Yokoi (2022) [65] | 4 | 1 | 1 | Poor |
| Giani (2022) [28] | 4 | 1 | 2 | Good |
| Ferreira (2024) [31] | 4 | 1 | 1 | Poor |
| Gao (2025) [36] | 4 | 1 | 2 | Good |
| Kotek (2024) [32] | 4 | 0 | 2 | Poor |
| Parnasa (2025) [37] | 3 | 1 | 2 | Good |
| Zhou (2024) [63] | 4 | 1 | 1 | Poor |
| Wei (2024) [66] | 4 | 1 | 1 | Poor |
Thresholds for converting Newcastle Ottawa Scale to AHRQ standards
• Good quality: 3 or 4 stars in selection domain AND 1 or 2 stars in comparability domain AND 2 or 3 stars in outcome/exposure domain
• Fair quality: 2 stars in selection domain AND 1 or 2 stars in comparability domain AND 2 or 3 stars in outcome/exposure domain
• Poor quality: 0 or 1 star in selection domain OR 0 stars in comparability domain OR 0 or 1 stars in outcome/exposure domain
Evidence for the association between myosteatosis and severe postoperative complications (Clavien-Dindo ≥ III) is low to moderate certainty. Although several higher-quality studies show a significant association—particularly in colon cancer—substantial heterogeneity in myosteatosis definitions, measurement techniques and outcome reporting warrants downgrading for inconsistency and indirectness.
Across all outcomes, the certainty of evidence is further limited by substantial heterogeneity in CT acquisition protocols, diagnostic thresholds for myosteatosis, and inadequate adjustment for clinical and lifestyle confounders.
Discussion
This review synthesises 54 observational studies evaluating the prognostic and postoperative impact of myosteatosis in colorectal cancer (CRC). In 2023, Chang et al. conducted a systematic review and meta-analysis of 10 studies, finding a significant association between myosteatosis in stage I–IV colorectal cancer and OS (HR 1.52), CSS (HR 1.67), and RFS (HR 1.89) [70]. In contrast to these outcomes, we found that when focusing on populations with non-metastatic disease only, the evidence is heterogenous and nuanced.
Our research adds the notable observation that the prognostic effect of myosteatosis in colon and rectal cancer appears to vary. A significant impact of myosteatosis was seen in CRC; however, subgroup analysis revealed more consistent observations of reduced survival in colon cancer compared to rectal cancer, in both OS and DFS. There was a paucity of cancer subtype-specific analysis, especially in CSS and DFS. Myosteatosis in colon cancer was observed to impact OS with HR up to 1.90 in one study of good methodological reliability [13]. Notably, treatment regimens for colon cancer (CC) and rectal cancer (RC) differ significantly, with neoadjuvant chemotherapy efficacy well-established in rectal cancer and potentially acting as a confounding variable [71]. Further studies examining the two cancer subtypes separately will be required to clarify the impact of myosteatosis as a prognosticator.
The evidence to support an association between myosteatosis and postoperative outcomes in CRC was inconsistent. Studies examining the outcome of overall postoperative outcomes were most numerous; however, the evidence was not suggestive of a clear link. As identified by an earlier systematic review by van Helsdingen et al. this may be attributed to the heterogeneity in the types of postoperative complications that are found reported among these studies [4]. To build upon this, we have attempted to narrow the outcome of postoperative complications to include three more specific indicators of postoperative course.
The studies examining severe (Clavien-Dindo III and above) complications demonstrated a consistent correlation, with a particularly consistent correlation observed in colon cancer. In colon cancer, Xiao et al. reported a hazard ratio of 2.42 for severe complications in patients with myosteatosis [47]. Given the morbidity and cost impacts of postoperative complications graded as Clavien-Dindo 3 and above, the increased risk of such magnitude may be relevant in surgical decision-making [72]. However, there is a need for further research to validate this finding. The evidence surrounding the complications of anastomotic leak was inconsistent in mixed CRC populations, but significant findings emerged in colon cancer in sub-type analysis. The evidence regarding LoS was ambiguous in its clinical significance, with magnitudes of differences in mean LoS reported as 1 day.
The mechanism behind the worsened OS outcome and predisposition for severe postoperative complications has not been fully elucidated. An interplay between systemic inflammation, nutritional status, and body composition has been proposed, suggesting that myosteatosis may reflect a broader catabolic state that leads to metabolic dysfunction and cancer cachexia [73, 74]. Myosteatosis is associated with worsened physiological fitness, with studies demonstrating poorer outcomes in cardiac and respiratory disease, suggesting poorer physiological recovery from surgery [75]. However, further research into the exact cardio-respiratory complications experienced by patients of colon and rectal cancer surgeries is required to clarify this potential association.
This review has focussed on a qualitative approach, partly due to the wide variety of measures of myosteatosis found and the ongoing lack of consensus on a clear definition for this condition. Both Martin and Xiao’s definitions were widely used in studies from Europe and Asia. IMAT was used within the Netherlands and Brazil, while IMAC, based on the multifidus muscle, was evaluated in Japan. In general, the evidence to support the efficacy of SMD, using TAMA for measures of survival and psoas muscle for measures of postoperative complications, was most frequent in the literature. Some emerging evidence to support the use of IMAT and other volume-related measures was observed, but this was less abundant.
In addition to this, studies frequently analysed colon and rectal cancer populations together in analyses of postoperative outcomes and survival, despite major differences in their therapeutic approach. Furthermore, similar to an earlier review, this review identified heterogeneity in the statistical handling of outcomes [4]. Studies used a variety of approaches to statistical analysis of common outcomes, including multivariable/multivariate analyses involving adjusting factors selected through clinical or statistical approaches. Finally, this review identified a high risk of bias in many studies in this review, predominantly due to inadequate description and inclusion of confounding factors in multivariate analysis. We propose that multivariate analyses should consider the common confounding variables: age, sex, tumour stage and location, BMI, delivery of neoadjuvant or adjuvant therapy and surgical approach at a minimum, with lifestyle factors such as smoking also being important [76, 77]. This would improve the clinical applicability and reliability of the results. Furthermore, for survival analyses, we recommend for follow-up periods to surpass 5 years, the standard duration of follow-up and benchmark for achieving cure of cancer. Follow-up durations and loss-to-follow-up information should be clearly stipulated to improve reliability.
The majority of studies elected to utilise distinct cut-offs of radiological density to determine myosteatosis. However, current literature suggests that the radiological attenuation of muscles differs by age, gender, race and is specific to certain muscles [78, 79]. The heterogeneity observed in the results may be attributed to the inadequate consideration of these factors in the diagnosis of myosteatosis. Supporting this, in Cho et al.’s subgroup analysis of CRC patients, a significant association between myosteatosis and overall survival was only found in the below 75 age group, suggesting that the definition of myosteatosis should vary with age [60]. Given the difficulties associated with finding a definitive cut-off for these measurements, it has also been suggested that myosteatosis measurement should be continuous; although our review has not found clear evidence to suggest its efficacy, a relative paucity in studies utilising this approach underlines a need for further research.
We found that less than half of the studies specified the use of intravenous contrast and the specific parameters used to capture the CT images. CT attenuation of muscle is sensitive to the use of contrast and also to the exact vascular phase at which these images are taken, necessitating the creation of clear guidelines for scan acquisition and definition of the condition [80]. Future research should focus upon delineating clear descriptions of the methods used for scan acquisition to enable a clear definition to be synthesised.
Limitations
The primary limitation of this review is the heterogeneity among the included studies for both the methods used to assess body composition and the definitions applied. Therefore, a meta-analysis was not performed in this study. We also acknowledge that our literature search was limited to three databases and to studies in the English language. Furthermore, with many studies originating from Asia and Europe, the geological generalizability of the findings may be limited. A large proportion of the included studies were retrospective, which can limit the ability to establish definitive causal relationships between myosteatosis and outcomes.
Future directions
Future research should prioritise standardisation of CT acquisition protocols, measurement techniques and diagnostic thresholds, while stratifying analyses by colon and rectal cancer given their distinct surgical and oncological treatment pathways. Large, prospective, multicentre cohorts with robust adjustment for confounders—including lifestyle factors and neoadjuvant and adjuvant therapies—are required to clarify prognostic significance.
Conclusion
A review of 54 studies conducted on the prognostic effect of myosteatosis on postoperative course and survival in colorectal cancer was conducted. Myosteatosis has a negative association with OS, with consistent effects observed in colon cancer. There is a negative association with severe postoperative outcomes, particularly in colon cancer.
These results are limited by the risk of bias and heterogeneity in measurement methods and statistical analysis. Future work is required to clarify the scan acquisition protocol and diagnostic criteria.
Supplementary Information
Below is the link to the electronic supplementary material.
(DOCX 79.9 KB)
Author contribution
CH and JZ collected and curated data. CH and JZ drafted the original manuscript. RK, MW and JY critically reviewed the manuscript for intellectual information. All authors edited the manuscript. JY was responsible for conception and design. JY supervised the study. All authors read and approved the final version of the manuscript. CH and JZ contributed equally and are equal first authors.
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Data availability
All data used in this study were obtained from previously published articles identified through the systematic review process. The datasets generated and analysed during the current study are available within the article and its supplementary materials. No additional raw data were generated or analysed beyond those reported.
Declarations
Conflict of interests
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Chloe Han and Junyao Zhang contributed equally and are equal first authors to this work.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
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Data Availability Statement
All data used in this study were obtained from previously published articles identified through the systematic review process. The datasets generated and analysed during the current study are available within the article and its supplementary materials. No additional raw data were generated or analysed beyond those reported.


