Background Body composition may partially explain the U-shaped association between BMI and colorectal cancer (CRC) survival. Methods Muscle and adiposity at CRC diagnosis and survival were examined in a retrospective cohort using Kaplan Meier curves, multivariable Cox regression, and restricted cubic splines in 3,262 early stage (I-III) male (50%) and female (50%) patients. Sarcopenia was defined using optimal stratification and sex- and BMI-specific cut points. High adiposity was defined as the highest tertile of sex-specific total adipose tissue (TAT). Primary outcomes were overall mortality (OM) and CRC specific mortality (CRCsM). Results Forty-two percent of patients were sarcopenic. During 6.0 years of follow-up, 788 deaths occurred, including 433 from CRC. Sarcopenic patients had a 27% (HR 1.27; 95% CI 1.09, 1.48) higher risk of OM, than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of OM (HR 1.64; 95% CI 1.05, 2.57) when compared to females with adequate muscle and lower adiposity. The lowest risk of OM was seen in patients with a BMI between 25-<30-kg/m2, a range associated with the greatest number of patients (58.6%) who were not at increased risk of OM due to either low muscle or high adiposity. Conclusions Sarcopenia is prevalent among non-metastatic CRC patients, and should, along with adiposity be a standard oncological marker. Impact Our findings suggest a biological explanation for the obesity paradox in CRC and refute the notion that the association between overweight and lower mortality is due solely to methodological biases.

Prediagnosis inflammation was associated with at-diagnosis sarcopenia. Sarcopenia combined with inflammation nearly doubled risk of death, suggesting that these commonly collected biomarkers could enhance prognostication. A better understanding of how the host inflammatory/immune response influences changes in skeletal muscle may open new therapeutic avenues to improve cancer outcomes.

Importance Physicians and investigators have sought to determine the relationship between body mass index (BMI) and colorectal cancer (CRC) outcomes, but methodologic limitations including sampling selection bias, reverse causality, and “collider” bias have prevented the ability to draw definitive conclusions. Objective We evaluated the impact of BMI at the time of, and following colorectal cancer (CRC) diagnosis, on mortality in a complete population using causal diagrams. Design Retrospective observational study with prospectively collected data Setting Kaiser Permanente Northern California Participants 3,408 men and women diagnosed 2006-2011 with stages I-III colorectal cancer who had surgery Exposures BMI at diagnosis, and 15 months following diagnosis Main Outcomes and Measures Hazard ratios for all-cause and CRC-specific mortality, relative to normal-weight patients, adjusted for sociodemographics, disease severity, treatment, and pre-diagnosis BMI. Results At-diagnosis BMI was associated with all-cause mortality in a nonlinear fashion, with underweight (BMI<18.5 kg/m2, hazard ratio [HR]=2.65, 95% confidence interval [CI]:1.63-4.31) and class II/III obese (BMI≥35 kg/m2, HR=1.33, 95% CI: 0.89-1.98) patients exhibiting elevated mortality risks, compared with low normal-weight (BMI 18.5-<23 kg/m2) patients. In contrast, high-normal-weight (BMI 23-<25 kg/m2, HR=0.77, 95% CI: 0.56-1.06), low-overweight (BMI 25-<28 kg/m2, HR=0.75, 95% CI:0.55-1.04), and high-overweight (BMI 28-<30 kg/m2, HR=0.52, 95% CI: 0.35-0.77) patients had lower mortality risks, and class I obese (BMI 30-<35 kg/m2) patients showed no difference in risk. Spline analysis confirmed a U-shaped relationship in participants (p-value, test for nonlinearity<0.001) with lowest mortality at BMI=28 kg/m2. Associations with CRC-specific mortality were similar. Associations of post-diagnosis BMI and mortality were also similar, but class I obese had significantly lower all-cause and cancer-specific mortality risks. Conclusions and Relevance Overweight patients consistently had the lowest mortality after a CRC diagnosis. Though strong scientific evidence shows that exercise in cancer patients should be encouraged, findings suggest, among overweight CRC patients, that recommendations for weight loss in the immediate post-diagnosis period may be unwarranted.

IMPORTANCE Given the risks of postoperative morbidity and its consequent economic burden and impairment to patients undergoing colon resection, evaluating risk factors associated with complications will allow risk stratification and the targeting of supportive interventions. Evaluation of muscle characteristics is an emerging area for improving preoperative risk stratification.OBJECTIVE To examine the associations of muscle characteristics with postoperative complications, length of hospital stay (LOS), readmission, and mortality in patients with colon cancer. DESIGN, SETTING, AND PARTICIPANTSThis population-based retrospective cohort study was conducted among 1630 patients who received a diagnosis of stage I to III colon cancer from January 2006 to December 2011 at Kaiser Permanente Northern California, an integrated health care system. Preliminary data analysis started in 2017. Because major complication data were collected between 2018 and 2019, the final analysis using the current cohort was conducted between 2019 and 2020.EXPOSURES Low skeletal muscle index (SMI) and/or low skeletal muscle radiodensity (SMD) levels were assessed using preoperative computerized tomography images. MAIN OUTCOMES AND MEASURESLength of stay, any complication (Ն1 predefined complications) or major complications (Clavien-Dindo classification score Ն3), 30-day mortality and readmission up to 30 days postdischarge, and overall mortality. RESULTSThe mean (SD) age at diagnosis was 64.0 (11.3) years and 906 (55.6%) were women. Patients with low SMI or low SMD were more likely to remain hospitalized 7 days or longer after surgery (odds ratio [OR], 1.33; 95% CI, 1.05-1.68; OR, 1.39; 95% CI, 1.05-1.84, respectively) and had higher risks of overall mortality (hazard ratio, 1.40; 95% CI, 1.13-1.74; hazard ratio, 1.44; 95% CI, 1.12-1.85, respectively). Additionally, patients with low SMI were more likely to have 1 or more postsurgical complications (OR, 1.31; 95% CI, 1.04-1.65) and had higher risk of 30-day mortality (OR, 4.85; 95% CI,. Low SMD was associated with higher odds of having major complications (OR, 2.41; 95% CI, 1.44-4.04).CONCLUSIONS AND RELEVANCE Low SMI and low SMD were associated with longer LOS, higher risk of postsurgical complications, and short-term and long-term mortality. Research should evaluate whether targeting potentially modifiable factors preoperatively, such as preserving muscle mass, could reverse the observed negative associations with postoperative outcomes.