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Objective:
Different indices of body composition have been shown to be associated with outcomes in patients with colorectal cancer (CRC), but little is known about their value in predicting the risk of incident disease. We aimed to investigate the associations of prediagnostic sarcopenia, myosteatosis, and visceral fat in relation to the risk of incident CRC.

Materials and Methods:
We included patients registered in an institutional biobank who underwent abdominal CT and were free from any cancer or inflammatory bowel disease prior to the CT scan or within 90 days thereafter. Body composition metrics including skeletal muscle area (SMA), visceral fat area (VFA), subcutaneous fat area (SFA), and mean skeletal muscle attenuation at the level of the L3 vertebra were extracted using a previously published, fully automated, deep learning algorithm. Sarcopenia was defined using skeletal muscle index, calculated as SMA divided by height squared (< 50 cm²/m² for men, < 39 cm²/m² for women). Myosteatosis was defined as skeletal muscle attenuation < 41 mean HU for body mass index BMI < 25 kg/m2 and < 33 HU for BMI = 25 kg/m². Diagnosis of CRC was defined using the ICD-9 and ICD-10 diagnosis codes of hospital encounters, and secondary outcomes included CRC according to subsite (proximal colon, distal colon, and rectal cancer). Patients were followed until the date of diagnosis of CRC, last encounter, or death, whichever came first. Cox proportional hazard regression models were used to estimate the hazard ratio (HR) and 95% CI of incident CRC in relation to the VFA/SFA ratio, sarcopenia, and myosteatosis, adjusting for age, sex, race, Charlson Comorbidity Index, smoking status, and BMI.

Results:
Among 7910 patients (median age, 54 years [IQR, 43 - 64 years]; women, 53.4%) included in this study, 31.9% had myosteatosis, and 26.1% had sarcopenia. We documented 151 incident CRC cases, 34 proximal colon cancer, and 57 distal colon and rectal cancers over 83,566 person-years. Myosteatosis (HR, 1.57; 95% CI, 1.10 - 2.25) and sarcopenia (HR, 1.77; 95% CI, 1.25 - 2.52) were each significantly associated with an increased risk of CRC after multivariable adjustment. A joint analysis of myosteatosis and sarcopenia showed that patients with both myosteatosis and sarcopenia were at the highest risk of CRC (HR, 2.55; 95% CI, 1.60 - 4.05), compared to those who had neither myosteatosis nor sarcopenia. Higher VFA-to-SFA ratio (HR, 1.38; 95% CI, 1.06 - 1.80) and myosteatosis (HR, 1.84; 95% CI, 1.03 - 3.27) were associated with an increased risk of distal colon and rectal cancers, but no significant associations were observed for proximal colon cancer.

Conclusion:
Myosteatosis and sarcopenia on abdominal CT scans are risk factors for incident CRC. Higher visceral fat was associated with an increased risk of distal colon and rectal cancers. These findings support that body composition analysis on abdominal CT can contribute to informing individualized CRC risk.