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Published on: February 12, 2022
Total Neoadjuvant Therapy With Long-Course Radiotherapy Versus Chemoradiotherapy in High-Risk Locally Advanced Rectal
Xin Wang1, Yuanling Tang1, Junyang Lu2
1Division of Abdominal Tumor Multimodality Treatment, Department of Radiation Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Total neoadjuvant therapy (TNT) with doublet chemotherapy and long-course radiotherapy improved disease-free survival in high-risk rectal cancer patients. This intensified regimen offers better outcomes than conventional chemoradiotherapy with manageable toxicity.
Area of Science:
- Oncology
- Gastrointestinal Cancer Research
- Clinical Trial Analysis
Background:
- High-risk locally advanced rectal cancer (LARC) is associated with a significant risk of distant recurrence, impacting disease-free survival (DFS).
- Conventional neoadjuvant chemoradiotherapy (nCRT) is a standard treatment, but intensified neoadjuvant approaches are being explored to improve outcomes.
Purpose of the Study:
- To compare the efficacy and safety of total neoadjuvant therapy (TNT) integrating long-course radiotherapy (LCRT) with uninterrupted doublet chemotherapy (doublet-LC TNT) versus conventional nCRT in patients with high-risk LARC.
Main Methods:
- A multicenter, randomized, phase III trial (NCT03177382) enrolled patients with stage II/III LARC and at least one high-risk feature.
- Patients were assigned to either doublet-LC TNT (induction, concurrent, and consolidation capecitabine plus oxaliplatin with LCRT) before surgery, or nCRT (capecitabine with LCRT) followed by surgery and adjuvant chemotherapy.
- The primary endpoint was disease-free survival (DFS).
Main Results:
- The doublet-LC TNT group showed a significantly improved 3-year DFS (74.8% vs. 66.0%; HR, 0.674; P = .016).
- Metastasis-free survival (MFS) and pathologic complete response (pCR) rates were significantly higher in the doublet-LC TNT arm (MFS: 77.7% vs. 67.6%; pCR: 26.37% vs. 9.80%).
- Locoregional failure rates were comparable, and while neoadjuvant grade ≥3 adverse events were more frequent with doublet-LC TNT, overall severe toxicities and major postoperative complications were similar between groups.
Conclusions:
- Doublet-LC TNT significantly improves DFS, MFS, and pCR rates compared to conventional nCRT in high-risk LARC patients, with manageable toxicity.
- These findings support doublet-LC TNT as a potential standard option within the modern TNT paradigm for LARC.
- Further research is needed to compare doublet-LC TNT with other TNT regimens, including those based on short-course radiotherapy or non-doublet concurrent chemotherapy.
