De-escalated total neoadjuvant therapy for the non-operative management of rectal cancer: Results of the NOM-3/TNT prospective cohort study.

BACKGROUND AND PURPOSE: Total neoadjuvant therapy (TNT) enables non-operative management, although at the cost of increased toxicity. We evaluated a de-escalated TNT-based watch-and-wait (w-w) regimen aimed at reducing toxicity and improving oncological safety through early surgery for poor-responding tumours.

MATERIAL AND

METHODS

Patients with small and intermediate-sized low-lying tumours (cT2-3/T4b N0-2) received short-course radiotherapy followed by 12 weeks of consolidation FOLFOX4. Initial tumour response assessment was performed at the midpoint of chemotherapy (six weeks).

RESULTS

Twenty-four patients were included. Based on the initial tumour response assessment, chemotherapy was discontinued in six (25%) patients, including one witha clinical complete response (cCR) and five with a poor response. Grade 3-4 acute toxicity was 17% in the 6-week chemotherapy group and 33% in the 12-week chemotherapy group. Following the initial and second (final) assessments, 16 (66%) patients initiated w-w (eight with cCR and eight with near-cCR), while eight (33%) with a poor-responding/persistent tumour proceeded to total mesorectal excision (TME). Regrowth occurred in seven (44%) patients, including one (13%) of eight who achieved cCR and six (75%) of eight who achieved near-cCR. Five patients with regrowth proceeded to salvage TME, whereas the remaining two refused TME. With a median follow-up of 20 months, sustained cCR at 2 years was 36% (95% confidence interval [CI]: 16-56) and organ preservation adapted disease-free survival 66% (95% CI: 45-87).

CONCLUSION

Our results suggest that the four-tier classification of tumour response (poor response at the midpoint of chemotherapy, persistent tumour, near-cCR and cCR) may reduce toxicity in selected patients.