Prolonged neoadjuvant chemotherapy without radiation versus total neoadjuvant therapy for locally advanced rectal cancer: A propensity score matched study

BACKGROUND: Although neoadjvuant chemoradiotherapy (CRT) improves the local control rate of locally advanced rectal cancer (LARC), it fails to significantly improve disease-free survival (DFS) and overall survival (OS). We explored the efficacy of prolonged neoadjuvant chemotherapy (pNCT) without radiation and compared this schema with total neoadjuvant therapy (TNT). MATERIAL AND METHODS: Patients diagnosed with LARC and received TNT (4 cycles of induction CapeOX/FOLFOX followed with CRT) or pNCT (6~8 cycles of CapeOX/FOLFOX) between June 2016 and October 2021 were retrospective analyzed. All patients underwent total mesorectal excision (TME). A 1:1 propensity score match was performed to adjust baseline potential confounders. The tumor response, toxicity, recurrence-free survival (RFS) and OS were observed. RESULTS: A total of 184 patients with 92 patients in each group were finally enrolled. The median follow-up time was 35 months. TNT showed better pathological complete response (pCR) rate (25.0% vs 16.3%) and objective regression rate (73.9% vs 59.8%) than pNCT. TNT and pNCT produce similar 3-year RFS and OS rates in patients with mid-to-upper rectal cancer. TNT was associated with improved tumor responsiveness in all patients and improved 3-year RFS rates in those with low rectal cancer. CONCLUSION: pNCT is an option for patients with mid-to-upper rectal cancer, but radiation is still necessary for low rectal cancer. To determine optimal schema for neoadjuvant therapy and patient selection, additional randomized controlled studies are needed.