Background
International, multicentre, open-label, randomized phase 2/3 organ-preservation trial (503 enrolled; modified ITT 409) in early- and intermediate-stage rectal adenocarcinoma (mrT1–T3bN0). Compared two radiotherapy-based organ-preservation strategies against primary total mesorectal excision (TME) to increase organ preservation without compromising oncologic control.
Results
Interventions and follow up: Arm A: LCCRT-OP — long-course chemoradiotherapy, 50 Gy in 25 fractions + capecitabine 825 mg/m² twice daily (n=163)
Arm B: SCRT-OP — short-course radiotherapy, 25 Gy in 5 fractions (n=168)
Arm C: primary TME (n=78)
Primary endpoint: organ preservation at 30 months (phase 3); phase 2 recruitment feasibility
mFollow up: 12-month interim implementation analysis
Results: TME-free survival (12-mo, organ-preservation arms): LCCRT 78.5% (95% CI 72.4–85.1) vs SCRT 60.6% (95% CI 53.6–68.4)
Interim HR (phase 2, LCCRT vs SCRT): 3.7 (95% CI 1.7–8.0) favoring LCCRT; posterior probability of superiority >99.5%
Overall TME-free survival (12-mo): 60%
Organ preservation at 30 mo (primary): NR
Arm B: SCRT-OP — short-course radiotherapy, 25 Gy in 5 fractions (n=168)
Arm C: primary TME (n=78)
Primary endpoint: organ preservation at 30 months (phase 3); phase 2 recruitment feasibility
mFollow up: 12-month interim implementation analysis
Results: TME-free survival (12-mo, organ-preservation arms): LCCRT 78.5% (95% CI 72.4–85.1) vs SCRT 60.6% (95% CI 53.6–68.4)
Interim HR (phase 2, LCCRT vs SCRT): 3.7 (95% CI 1.7–8.0) favoring LCCRT; posterior probability of superiority >99.5%
Overall TME-free survival (12-mo): 60%
Organ preservation at 30 mo (primary): NR
Adverse events
Toxicity/quality-of-life (mature): NR at this 12-month interim analysis
Design intent: reduce surgical morbidity, stoma, and QoL harms of TME
Design intent: reduce surgical morbidity, stoma, and QoL harms of TME
Conclusions
At 12 months, long-course chemoradiotherapy achieved substantially higher TME-free survival than short-course radiotherapy for organ preservation in early/intermediate rectal cancer. The mature 30-month organ-preservation primary endpoint is pending; these interim data favor LCCRT as the preferred organ-preservation backbone.
Key Limitations
This is a 12-month interim implementation analysis triggered by early phase 2 superiority; the definitive phase 3 organ-preservation endpoint at 30 months is not yet reported. Partially randomized patient-preference design in phase 3 introduces selection effects; open-label; long-term local recurrence and survival data immature.
Clinical Context
Organ preservation (watch-and-wait after neoadjuvant therapy) is an emerging alternative to upfront TME for suitable early/intermediate rectal cancers, endorsed as an option by NCCN and ESMO in selected patients. STAR-TREC informs which radiotherapy schedule maximizes organ preservation; no regulatory action involved.