GI Lower
Organ preservation in MRI node-negative early rectal cancer: randomised data on which RT schedule to pair with a watch-and-wait strategy.
STAR-TREC
ForRectal adenocarcinoma ≤40 mm, mrT1-T3bN0, no EMVI, ECOG 0-1
78.5% vs 60.6%
HR 1.90 (95% CI 1.29-2.81); 30-mo organ-preservation 1° EP not yet reported
TL;DR12-mo TME-free survival 78.5% vs 60.6% (HR 1.90) favouring LCCRT over SCRT for organ preservation in mrT1-T3bN0 rectal cancer ≤40 mm.
RT delivery does not explain the gap: completion was 99% with LCCRT and 100% with SCRT, with 18 (11%) needing a capecitabine dose change, so the difference tracks fractionation plus concurrent chemo, which this design cannot separate. Nodes in 22% of TME specimens despite MRI N0 make mesorectal coverage relevant; target volume is not in source text.
In MRI node-negative rectal adenocarcinoma ≤40 mm (mrT1-T3bN0) choosing organ preservation, this supports LCCRT over SCRT as the response-adapted backbone at 12 mo; it does not extend to EMVI-positive, node-positive, or >40 mm tumours. The longer read
RT delivery does not explain the gap: completion was 99% with LCCRT and 100% with SCRT, so the TME-free survival difference tracks fractionation plus concurrent capecitabine, which this design cannot separate. Nodes in 22% of TME specimens despite MRI N0 make mesorectal coverage relevant; target volume is not in source text.
Primary TME carried G≥3 SAEs in 18%, anastomotic-leak perforation in 15% and one death, and 86% of phase 3 pts chose organ preservation. LCCRT-OP kept more pts TME-free at 12 mo, but nodes in 22% of TME specimens despite MRI N0 frame the surveillance and salvage question.
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Open-label, randomised phase 2/3 at 37 sites in five European countries. Phase 2 randomised 1:1:1 to LCCRT-OP, SCRT-OP or primary TME (N=120); phase 3 used a partially randomised patient-preference design, with OP choosers randomised 1:1. Bayesian framework; this 12-month analysis covers 426 pts recruited before Aug 8, 2023 (409 mITT).
Rectal adenocarcinoma ≤40 mm, mrT1-T3bN0 on MRI, ECOG 0-1, with primary TME judged reasonable. Excluded: MRI nodal involvement or EMVI, tumour within 1 mm of the mesorectal fascia, anterior tumours above the peritoneal reflection, predominantly mucinous histology, metastases. mrT2 in 242 (73%) OP pts; 266 (80%) below the peritoneal reflection.
LCCRT-OP: 50 Gy in 25 fractions with oral capecitabine 825 mg/m² twice daily. SCRT-OP: 25 Gy in five fractions. Response assessed at 16-20 weeks with TAE for near-complete response; target volume not in source text.
Phase 2 primary: feasibility, recruitment at months 12 and 24 against thresholds of ≥4 and ≥6 randomisations/month (achieved 3 and 6). Phase 3 primary: organ preservation at 30 months (no TME, stoma or local recurrence), not yet reported. This analysis reports 12-month TME-free survival, response and safety.
Phase 2 alone gave HR 3.7 (95% CI 1.7-8.0), with median TME-free survival 7.6 mo after SCRT-OP vs not reached after LCCRT-OP; pooling phase 3 pulled the estimate toward the null.
| Endpoint | LCCRT-OP (n=163) | SCRT-OP (n=168) | Effect |
|---|---|---|---|
| TME-free survival | 78.5% (95% CI 72.4-85.1) | 60.6% (53.6-68.4) | HR 1.90 (1.29-2.81), posterior P >99.5% |
| cCR at 16-20 wk | 104 (64%) | 61 (36%) | not reported |
| TAE for near-cCR | 38 (23%) | 68 (40%) | not reported |
| Endpoint | LCCRT-OP | SCRT-OP | Primary TME |
|---|---|---|---|
| G3-4 GI SAEs | 4 (2%) | 6 (4%) | 6 (8%) |
| G3-4 procedural SAEs | 3 (2%) | 5 (3%) | 5 (6%) |
| G≥3 SAEs within 4 wk of RT/CRT | 9/163 (6%) | 2/168 (1%) | n/a |
Primary TME: G≥3 SAEs in 14 (18%) of 78, intraperitoneal perforation from anastomotic leak in 12 (15%), and one postoperative death from sepsis. After TAE, perineal fistulation occurred in two (1%) OP pts. Capecitabine dose modification in 18 (11%) of 161.
At design, primary TME without neoadjuvant therapy was standard for this population. OPRA addressed watch-and-wait after neoadjuvant therapy in locally advanced disease; STAR-TREC is a randomised test of which radiation schedule best supports response-adapted organ preservation in smaller, node-negative tumours.
The shrinking HR from phase 2 to the pooled cohort suggests early overestimation, and phase-difference analyses are exploratory post-hoc. Occult nodes in 17 (22%) TME specimens imply MRI N0 misses nodal disease that organ-preserving arms never sample. Median follow-up was 34 and 35 mo, but outcomes were censored at 12 mo.
At 12 months, a longer RT course with capecitabine buys more complete responses and fewer TMEs than SCRT, at the cost of more acute SAEs. What it does not settle is durable organ preservation, local regrowth and function, all tied to the 30-month endpoint.
Governance-led interim at 12 mo; prespecified 30-mo organ-preservation endpoint not yet reached. Open-label, TME-free survival only, TME comparison non-randomised in phase 3.
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