Multicenter phase 3 trial of SCRT-based total neoadjuvant therapy versus standard long-term CRT for LARC: five-year outcomes of STELLAR

The multicenter phase 3 STELLAR trial in China compared neoadjuvant short-course radiotherapy followed by chemotherapy (SCRT-based total neoadjuvant therapy; TNT) versus standard long-course chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). Five-year results of STELLAR have now been published. Patients with distal or middle-third LARC were randomized to receive either SCRT-based TNT or CRT. At a median follow-up of 68.7 months, the 5-year disease-free survival (DFS) rate was 62.0% in the TNT group and 58.7% in the CRT group (HR 0.849; 95% CI 0.662-1.089), with 5-year overall survival (OS) rate of 78.1% versus 69.7% (0.739; 0.550-0.993), respectively. Distant metastasis (DM) and locoregional recurrence (LRR) rates were similar between the groups. Among high-risk patients (ESMO criteria), TNT was associated with improved OS (HR 0.663; 95% CI 0.469-0.397) and showed a nonsignificant trend toward improved DFS (0.765; 0.568-1.032). In patients with DM or LRR, TNT was associated with both improved postrecurrence progression-free survival (HR 0.691; 95% CI 0.497-0.961) and postrecurrence survival (0.698; 0.490-0.994). The authors conclude that these results suggest that SCRT-based TNT provides a durable survival advantage and is a viable alternative to SCRT, especially in patients with high-risk disease.