However, as stated previously, both the CAIRO and the UK MRC FOCUS trials fulfill the requirements set by Simon et al. (81) in order to obtain LoE 1 for a predictive biomarker of irinotecan efficacy, and the trials still represent the best available option to retrospectively assess the association between other biomarkers or Top1 analyzed by techniques other than IHC and irinotecan in the advanced setting of CRC. Here, TOP1 is linked to colorectal carcinoma.