Boakye D, Walter V, Martens UM, et al. - Stage II-III colorectal cancer patients diagnosed in 2003 to 2014 and enrolled into a population-based study were involved (N = 1,102) in order to evaluate that to what extent comorbidities and functional status (FS) affect treatment decisions in colorectal cancer patients and describe the advantage of chemotherapy in stage III colon cancer (CC) patients. The Charlson comorbidity scores 1, 2 and 3+ were related to 57%, 66% and 70% lower odds of chemotherapy use, respectively, in stage II (high-risk) and III CC patients. In combination with elderly age and poor FS, comorbidity was correlated with 97% and 83% reduced odds of adjuvant chemotherapy use in CC and rectal cancer patients, respectively. In stage III CC patients, lower comorbidity and higher FS defined 38% and 24% of the overall and disease-specific survival advantages of chemotherapy, respectively. Selection bias was noted even in the comprehensive models, as chemotherapy was still related to substantially higher non-disease-specific survival, mainly in patients < 75 years. Thus, in stage III CC patients, lower comorbidity and higher FS of recipients of chemotherapy deine nearly 40% of the advantage of chemotherapy. Irrespective of how comprehensive propensity score analyses could be in observational studies, treatment selection bias might continue and influence estimates of treatment effects.