Treatment of locally advanced rectal cancer (LARC) involves a multidisciplinary approach. The standard of care in most high-income countries consists of neoadjuvant chemoradiotherapy followed by total mesorectal excision and adjuvant chemotherapy.
1-4 However, only two-thirds of patients receive planned adjuvant chemotherapy because of postoperative or ostomy-related complications or patients’ preference.
5 Some pilot and phase 2 single-arm studies
6-8 followed by randomized clinical trials (RCTs)
9-12 investigated the role of total neoadjuvant therapy (TNT), which is preoperative chemotherapy in addition to radiotherapy. According to the rationale of these studies, the advantages of preoperative chemotherapy include better adherence, early treatment of micrometastases, and higher pathological complete response (pCR) rates.
11,13 The initial results of these studies were extremely encouraging, showing high pCR rates, and TNT protocols were rapidly incorporated in some US guidelines,
2,14 even though results on locoregional and distant recurrence rates, disease-free survival (DFS), and overall survival (OS) were not yet available.