Total Neoadjuvant Therapy With Long-Course Radiotherapy Versus Chemoradiotherapy in Locally Advanced Rectal Cancer

In the randomised phase III TNTCRT trial (n = 458), total neoadjuvant therapy combining long-course radiotherapy with uninterrupted doublet chemotherapy improved 3-year disease-free survival compared with conventional neoadjuvant chemoradiotherapy: 74.8% versus 66.0% (HR 0.674; 95% CI 0.489 to 0.929; P = .016) at a median follow-up of 51 months. Metastasis-free survival (77.7% versus 67.6%; HR 0.655; 95% CI 0.469 to 0.915) and pathologic complete response rates (26.37% versus 9.80%; P < .001) were also higher, while locoregional failure remained low and comparable between arms (6.03% versus 6.19%). The cost is toxicity during the neoadjuvant phase - grade 3 or higher adverse events in 27.59% versus 8.56% of patients - although across the whole treatment course the difference narrows (28.02% versus 24.32%), and major postoperative complications were similar (3.98% versus 2.94%). Patients had stage II/III rectal cancer with at least one high-risk feature (cT4a-b, cN2, mesorectal fascia involvement, or cT3c-d with extramural vascular invasion).