Background
Phase III randomized trial. 326 patients with T3 rectal cancer requiring abdominoperineal resection or low anterior resection. Compared short-course preoperative radiotherapy (SCRT) with delayed surgery to long-course chemoradiotherapy (LCRT). Patients staged clinically; MRI staging not mandated. Primary objective: determine whether SCRT was equivalent to LCRT for local control.
Interventions and follow up
Arm A: SCRT: 25 Gy in 5 fractions over 1 week → delayed surgery at 4–8 weeks (interval chemotherapy between RT and surgery permitted per investigator discretion)
Arm B: LCRT: 50.4 Gy in 28 fractions over 5.5 weeks with concurrent continuous infusion 5-FU → surgery at 4–8 weeks after CRT completion
Primary endpoint: Local recurrence at 3 years
mFollow up: 5.9 years
Arm B: LCRT: 50.4 Gy in 28 fractions over 5.5 weeks with concurrent continuous infusion 5-FU → surgery at 4–8 weeks after CRT completion
Primary endpoint: Local recurrence at 3 years
mFollow up: 5.9 years
Results
Local recurrence (3-yr): 7.5% (SCRT) vs 4.4% (LCRT), HR 1.84 (95% CI 0.88–3.85), P=.24
OS (5-yr): 74% vs 70%, HR 0.91, P=.53
pCR: 1% (SCRT) vs 11% (LCRT)
Late toxicity grade ≥3: 5.8% vs 8.2%
OS (5-yr): 74% vs 70%, HR 0.91, P=.53
pCR: 1% (SCRT) vs 11% (LCRT)
Late toxicity grade ≥3: 5.8% vs 8.2%
Adverse events
Late toxicity: Grade ≥3 late toxicity 5.8% (SCRT) vs 8.2% (LCRT)
Acute/surgical: Acute grade ≥3 toxicity not significantly different between arms; bowel dysfunction and postoperative complication rates comparable
Acute/surgical: Acute grade ≥3 toxicity not significantly different between arms; bowel dysfunction and postoperative complication rates comparable
Conclusions
SCRT with delayed surgery produced a 3-year local recurrence rate of 7.5% vs 4.4% with LCRT — an absolute difference of 3.1% that did not reach statistical significance (P=.24). OS was equivalent at 5 years. SCRT resulted in substantially lower pCR rates (1% vs 11%), reflecting inferior tumor downstaging.
Key Limitations
Key Limitations: Trial was underpowered for the absolute difference observed, raising uncertainty about true equivalence vs type II error — HR of 1.84 favors LCRT. pCR rates markedly different (1% vs 11%), suggesting inadequate downsizing with SCRT alone. Optional interval chemotherapy in the SCRT arm introduces heterogeneity and complicates interpretation. Trial predates modern MRI staging, total mesorectal excision quality assurance, and the TNT era — direct translation to current practice is limited.
Clinical Context
TROG 01.04 provided early evidence that SCRT with delayed surgery can achieve comparable local recurrence rates to LCRT, informing later TNT strategies (RAPIDO, STELLAR). The very low pCR rate with SCRT alone limits its use when organ preservation or significant downsizing is the goal. SCRT-based TNT with interval chemotherapy (as in RAPIDO/STELLAR) has since become the preferred approach in guidelines for high-risk LARC when TNT is selected.
References
References: Ngan SY et al, JCO 2012 (primary analysis)