[Current concepts of total neoadjuvant therapy for rectal cancer]

Total neoadjuvant therapy (TNT) refers to the addition of preoperative systemic therapy to preoperative radiotherapy (RT; 5 × 5 Gy) or chemoradiotherapy (ChRT) for rectal cancer. This can be administered either before RT/ChRT as induction therapy or after RT/ChRT as consolidation therapy. Randomized trials demonstrate improved tumor response (clinical or pathological complete remission) and a significant improvement in disease-free survival with TNT compared to neoadjuvant ChRT plus surgery with or without adjuvant chemotherapy. The updated S3 guidelines therefore recommend TNT, particularly for patients high-risk factors defined with magnetic resonance imaging (MRI, cT4, cN2, mrCRM+, EMVI+, lateral lymph node involvement). Following achievement of complete clinical remission after TNT organ-preserving (watch and wait) strategies are increasingly being favored and are being further optimized in ongoing clinical trials (e.g., ACO/ARO/AIO 18.1, JANUS, STELLAR II).