Multicenter phase 2 trial of total neoadjuvant therapy followed by non-operative management or surgery in stage II or III rectal cancer

Rectal surgery after total neoadjuvant therapy is a standard of care ofr pMMR/MSS stage II or III rectal cancer. In patients who have clinical complete response, non-operative management (avoidance or delay of surgery and intensive surveillance) may be an option. The phase 2 NO-CUT trial, at four centers in Italy, included patients with stage II or III pMMR/MSS adenocarcinoma of the lower-to-middle rectum, who underwent total neoadjuvant therapy. Patients with clinical complete response (26%) entered non-operative management, while patients without clinical complete response underwent surgery. After a median follow-up of 35 months (IQR 21-50), 30-months distant relapse-free survival rate was 95% (95% CI 88-100) in the non-operative management group and 74% (68-82) in the overall population. The authors conclude that in pMMR/MSS stage II or III rectal cancer, total neoadjuvant therapy followed by non-operative management allows organ preservation in some patients with compromising distant relapse-free survival.