Impact of body-mass index on treatment and outcome in locally advanced rectal cancer: A secondary, post-hoc analysis of the CAO/ARO/AIO-04 randomized phase III trial

Background: A better understanding of the impact of body-mass index (BMI) on the course of multimodal therapy and oncologic outcome in locally advanced rectal cancer could provide new insights for optimization of treatment and supportive strategies. Patients and methods: Correlations of BMI with pretreatment clinical, surgical, and pathological characteristics, toxicity and treatment adherence using the Pearson's Chi-squared test or logistic regression were analyzed in the CAO/ARO/AIO-04 III trial cohort (n = 1236). One-way ANOVA or Welch test were used to analyze correlations of baseline blood-parameters and BMI. The prognostic role of BMI was examined with log-rank test and multivariate cox regression. Results: Obese had a better ECOG performance status (P = 0.027) but were less likely to undergo sphincter preserving surgery (P = 0.01). Post-surgical complications did not differ significantly between BMI classes, whereas underweight was associated with increased neutrophil (P = 0.025) and platelet counts (P < 0.001), poorer TME quality (P = 0.007) and increased incidence of acute organ toxicity (P < 0.001). After a median follow-up of 50 months, underweight [HR 1.896, P = 0.014] and overweight [HR 1.392, P = 0.042] were associated with worse DFS. Obese patients had an increased risk of death [HR 1.653, P = 0.032]. Normalweight men showed superior OS compared to underweight [HR 4.070, P = 0.002], overweight [HR 2.077, P = 0.010], severe overweight [HR 1.886, P = 0.026] and obese [HR 2.046, P = 0.015] men. Adding oxaliplatin to standard CRT significantly improved DFS in obese patients (P = 0.034). Conclusion: In our study, underweight and overweight correlated with inferior DFS, underweight experienced more organ toxicity and obesity was associated with an increased risk of abdominoperineal resection and poorer overall survival.