KEY POINTS
- TNTCRT was a multicentre randomized phase III trial enrolling stage II–III rectal cancer with at least one high-risk feature: cT4a–b, cN2, mesorectal-fascia involvement, or cT3c–d disease with extramural venous invasion.
- Patients received either uninterrupted doublet total neoadjuvant therapy with induction, concurrent, and consolidation capecitabine plus oxaliplatin around long-course radiotherapy before surgery, or conventional capecitabine-based chemoradiotherapy followed by surgery and adjuvant chemotherapy.
- Between June 2017 and December 2023, 458 patients were randomized: 232 to doublet total neoadjuvant therapy and 226 to conventional treatment. Median follow-up was 51 months, and the primary endpoint was disease-free survival.
- Three-year disease-free survival was 74.8% versus 66.0%, an absolute improvement of 8.8 percentage points and a relative reduction in failure risk of approximately one third (HR 0.674, 95% CI 0.489–0.929; p=0.016).
- Three-year metastasis-free survival was 77.7% versus 67.6%, an absolute improvement of 10.1 percentage points (HR 0.655, 95% CI 0.469–0.915; p=0.014). Locoregional failure remained similar at 6.03% versus 6.19% (p=0.943).
- Pathological complete response increased from 9.80% to 26.37% (p<0.001), meaning complete eradication in the surgical specimen was approximately 2.7 times more frequent with doublet total neoadjuvant therapy.
- Grade ≥3 adverse events during neoadjuvant treatment were more common with doublet therapy (27.59% vs 8.56%, p<0.001), but rates across the complete treatment course were similar (28.02% vs 24.32%, p=0.371). Major postoperative complications were also comparable (3.98% vs 2.94%, p=0.567).
CLINICAL TAKEAWAY
This trial supports uninterrupted oxaliplatin-containing total neoadjuvant therapy as an effective option for biologically and anatomically high-risk locally advanced rectal cancer. The evidence is strong for disease-control improvement, but the regimen still requires comparison with contemporary short-course and alternative total neoadjuvant strategies.