Three S’s (sex, seniors, and sarcopenia) matter during chemotherapy for colorectal cancer

Recent progress in treatments has dramatically improved the outcomes of colorectal cancer (CRC).Neoadjuvant chemoradiotherapy (CRT) has been the standard therapy for resectable advanced cancer of the lower rectum, and the combination of additional systemic chemotherapy before or after CRT is attracting attention for further improvement of local antitumor effects.Patients with unresectable CRC have a good chance of conversion to resection after the use of key cytotoxic drugs, such as 5fluorouracil, oxaliplatin, and irinotecan, along with targeted antibodies.Furthermore, immune checkpoint inhibitors are available in these neoadjuvant settings.For adjuvant chemotherapy of localized CRC, the recommended treatment is 5-fluorouracil plus oxaliplatin.Meanwhile, accumulating evidence shows that sarcopenia is associated with adherence to and outcomes of these treatments.For instance, sarcopenia or skeletal muscle loss occurring before and during preoperative treatments predict poor prognosis in patients undergoing neoadjuvant CRT and those who received conversion therapy for unresectable CRC.Sarcopenia or skeletal muscle loss is also associated with dose-limiting toxicity and the outcomes of adjuvant chemotherapy.Importantly, unchangeable variables such as age and sex often determine sarcopenia and/or chemotherapy tolerability.This review describes the clinical significance of the three S's (sex, seniors, and sarcopenia) in chemotherapy/CRT used in various settings for CRC.