Perioperative (radio)chemotherapy for locally advanced rectal cancer

For patients with locally advanced rectal cancer (LARC) perioperative radiochemotherapy (RChT) has been recommended in German guidelines since the 1990s as a standard therapy. Neoadjuvant 5-fluorouracil (5-FU) based RChT was introduced 10 years ago as the standard of care instead of adjuvant RChT. The aim of the current overview is to discuss studies investigating the substitution of 5-FU by oral fluoropyrimidines, the relevance of adjuvant chemotherapy as well as the use of oxaliplatin and monoclonal antibodies in the perioperative treatment. Two studies demonstrated that capecitabine was non-inferior to intravenous 5-FU. Oxaliplatin has been investigated in the perioperative treatment in six large randomized trials and two of these trials have achieved the primary endpoint of prolonging disease-free survival (DFS): the Korean ADORE trial led to an improvement in DFS in high-risk patients receiving oxaliplatin in addition to 5-FU as postoperative therapy, while in the German CAO/ARO/AIO-04 study oxaliplatin was added to both neoadjuvant and adjuvant treatment also resulting in improved DFS. In contrast, the other four trials exhibited no benefits of perioperative oxaliplatin. Monoclonal antibodies have not been investigated in phase III trials in patients with LARC and should not be administered outside clinical trials. Capecitabin can replace 5-FU in the perioperative treatment of LARC. Data regarding the use of oxaliplatin are not congruent. The use of oxaliplatin only in conjunction with neoadjuvant RChT cannot be recommended, while data of the CAO/ARO/AIO-04 trial indicate that the preoperative and postoperative use of additional oxaliplatin may be regarded as a new treatment option. Consideration should be given to the additional use of oxaliplatin in high-risk patients in the postoperative treatment according to the data from the ADORE trial.