Total neoadjuvant therapy: A new standard of care for locally advanced rectal cancer?

Abstract

Delivering chemotherapy before surgery is a newer treatment approach called total neoadjuvant therapy (TNT), and the National Comprehensive Cancer Network guidelines recommend it for locally advanced rectal cancer (LARC) with cT3 / cN+ / cT4, in contrast with the European Society for Medical Oncology guidelines, in which most rectal cancers can be treated with surgery alone if good quality mesorectal resection is assured. Neoadjuvant or adjuvant treatments are reserved for patients with high-risk tumours, including cT3c/d or cT4, or that threaten the mesorectal fascia. The favourable outcomes in the RAPIDO trial for high-risk rectal cancers with a lower incidence of distant metastasis in the TNT group were observed but with an unexpected increase in the local recurrence with more extended follow-up. This suggests early surgery for nonresponding tumours. The TNT approach was also evaluated in the OPRA trial with long-course chemoradiotherapy and induction versus consolidation chemotherapy. Half the patients presented complete clinical responses and were enrolled in the watch-and-wait (WW) approach. Given the high number of trials and guidelines in this subject, the multidisciplinary team's decision-making process in rectal cancer management is complex. Looking at the actual data, it was concluded that TNT is not for all patients with LARC and is an option if organ preservation is a priority, although with a high regrowth rate in a WW strategy and increasing risk of distant metastasis, questioning the deleterious effect of deferral of surgery.