Intensified Total Neoadjuvant Therapy in Patients With Locally Advanced Rectal Cancer: Long-term Results of a Prospective Phase II Study.

Aims: To analyze the long-term results of a prospective phase II trial testing intensified total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC).

Materials and methods: Patients with histologically confirmed LARC adenocarcinoma were enrolled. Intensified TNT consisted of targeted agent (bevacizumab or panitumumab/cetuximab) plus FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) induction chemotherapy followed by intensified (oxaliplatin and 5-fluorouracil) chemoradiotherapy (CRT) and surgical resection. Follow-up data were collected for all patients included in the trial. Survival outcomes were calculated using the Kaplan-Meier method and curves were compared by the log-rank test.

Results: Between October 2015 and September 2019, 28 LARC patients were enrolled. Follow-up data were available for all included patients. In total, 11 (39.3%) patients had a complete response (CR). At 6.3 years (median follow-up), 5-year overall survival (OS) and DFS were 74.6% and 57.1%, respectively. Five-year OS was 80.8% for CR patients and 70.1% for no-CR patients (p-value 0.07). Those patients with CR after TNT treatment had a 5-year DFS of 81.8% versus 41.2% for those with no CR (p-value 0.015).

Conclusion: The addition of a targeted agent to induction FOLFOXIRI and oxaliplatin to 5-fluorouracil-based CRT, with the doses and intensities used in this study, resulted in high CR rates. Patients who achieve a CR demonstrate superior DFS compared to patients without CR. Intensified TNT may have the potential to increase survival outcomes. Further research on TNT strategies in LARC is encouraged.