KEY POINTS
- The multicentre open-label phase III STELLAR trial (NCT02533271) randomized 599 patients with magnetic resonance imaging-staged distal or middle-third, cT3–4 and/or node-positive rectal cancer to short-course total neoadjuvant therapy or conventional long-course chemoradiotherapy.
- The experimental strategy used 25 Gy in five fractions over one week, followed by four cycles of CAPOX before surgery. The control arm received 50 Gy in 25 fractions over five weeks with concurrent capecitabine before surgery.
- After a median follow-up of 68.7 months, five-year disease-free survival was 62.0% with short-course total neoadjuvant therapy and 58.7% with chemoradiotherapy, an absolute difference of 3.3 percentage points. The hazard ratio was 0.849 (95% CI 0.662–1.089).
- Five-year overall survival was significantly higher with short-course total neoadjuvant therapy: 78.1% versus 69.7%, an absolute improvement of 8.4 percentage points. The hazard ratio for death was 0.739 (95% CI 0.550–0.993).
- Rates of distant metastasis and locoregional recurrence were similar between groups. The survival advantage therefore was not accompanied by a statistically significant reduction in the initial risk of disease recurrence.
- Among patients classified as high risk according to European Society for Medical Oncology criteria, total neoadjuvant therapy improved overall survival with a hazard ratio of 0.663 (95% CI 0.469–0.937). Disease-free survival also favoured total neoadjuvant therapy, but the difference was not significant: HR 0.765 (95% CI 0.568–1.032).
- Among patients who developed distant metastasis or locoregional recurrence, assignment to total neoadjuvant therapy was associated with better post-recurrence progression-free survival (HR 0.691, 95% CI 0.497–0.961) and post-recurrence survival (HR 0.698, 95% CI 0.490–0.994).
- The original STELLAR analysis reported more grade 3–5 acute toxicity during preoperative treatment with total neoadjuvant therapy than with chemoradiotherapy, 26.5% versus 12.6%. The five-year abstract does not provide a new detailed analysis of late toxicity.
CLINICAL TAKEAWAY
Short-course radiotherapy followed by chemotherapy provides a durable and clinically meaningful overall survival advantage over conventional long-course chemoradiotherapy, particularly in patients with high-risk disease. However, disease-free survival and recurrence rates were similar, acute toxicity was higher in the original analysis, and the study did not evaluate a non-operative organ-preservation strategy.