GI Lower
Fractionation, not the decision to preserve, is what moved: long-course chemoRT doubled complete response over short-course in the watch-and-wait pathway.
STAR-TREC
ForRectal adenocarcinoma <40 mm, mrT1-T3bN0, ECOG 0-1, TME otherwise feasible
TL;DR12-mo TME-free survival 78.5% with LCCRT vs 60.6% with SCRT, HR 1.90 (1.29-2.81), in mrT1-T3bN0 rectal cancer.
For an RT reader the actionable number is the response gradient: cCR 64% with 50 Gy/25 fx plus capecitabine vs 36% with 25 Gy/5 fx, which is what drives the 78.5% vs 60.6% TME-free survival. Acute SAE grade ≥3 within 4 weeks of RT ran higher with LCCRT (6% vs 1%), so the trade is upfront toxicity for organ preservation.
In rectal adenocarcinoma under 40 mm staged mrT1-T3bN0 where TME is feasible and the patient wants organ preservation, this supports long-course chemoradiotherapy over short-course as the preservation schedule; it does not address node-positive, larger, or metastatic disease, and 30-month preservation is still unreported.
This is a randomised head-to-head of two schedules inside a preservation pathway: 50 Gy/25 fx plus capecitabine gave cCR 64% vs 36% with 25 Gy/5 fx at 16-20 weeks, driving TME-free survival 78.5% vs 60.6%. Acute grade ≥3 SAEs within 4 weeks of RT were 6% vs 1%, the cost of that gradient.
Concurrent capecitabine 825 mg/m² twice daily with 50 Gy/25 fx was well tolerated, with 18 (11%) of 161 needing at least one dose modification, and the chemoradiotherapy arm doubled cCR (64% vs 36%) over radiotherapy alone. The schedule choice, not systemic escalation, is what moves preservation here.
Response-adapted preservation kept 78.5% TME-free at 12 months after LCCRT, but transanal excision for near-complete response ran 40% after SCRT vs 23% after LCCRT, so the schedule changes how much local surgery you end up doing. 22% of TME specimens had positive nodes despite node-negative MRI.
12 details 4 trials watching
Open-label, international, multicentre, parallel-group, superiority phase 2/3 trial at 37 hospitals in the UK, Netherlands, Sweden, Denmark, and Belgium. Phase 2 randomised 1:1:1 (LCCRT-OP, SCRT-OP, TME); phase 3 used a partially randomised patient-preference design, with those choosing organ preservation randomised 1:1 between the two RT schedules, stratified by country and MRI T category.
Biopsy-confirmed rectal adenocarcinoma <40 mm staged mrT1-T3bN0, ECOG 0-1, aged ≥16 (UK) or ≥18 elsewhere. Excluded: diameter >40 mm, metastatic disease, MRI-defined nodal involvement or extramural venous invasion, tumour within 1 mm of mesorectal fascia, anterior tumours above the peritoneal reflection, mucinous histology. Median age 67, 72% male, 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. Completion was high in both groups: 159 (99%) of 161 LCCRT participants and 168 (100%) SCRT. 18 (11%) of 161 receiving LCCRT needed at least one capecitabine dose modification for toxicity.
Phase 3 primary: organ preservation 30 months after treatment initiation (absence of TME, stoma, or local recurrence), assessed in the mITT population and not reported in this analysis. This report gives the 12-month implementation outcomes: TME-free survival, clinical complete response at the second response assessment, and serious adverse events. Bayesian framework with Cox models for time-to-event outcomes.
Response-adapted decision-making at 16-20 weeks explains the divergence: cCR 64% vs 36% favoured LCCRT-OP while TAE for near-complete response was commoner after SCRT-OP (23% vs 40%), and the resulting TME-free survival gap was 78.5% vs 60.6%.
| Event | LCCRT-OP | SCRT-OP | Primary TME |
|---|---|---|---|
| Gastrointestinal disorders | 4 (2%) | 6 (4%) | 6 (8%) |
| Procedural complications | 3 (2%) | 5 (3%) | 5 (6%) |
Grade 3-4 serious adverse events were most often gastrointestinal (2% LCCRT vs 4% SCRT vs 8% TME) and procedural complications (2% vs 3% vs 6%). Grade ≥3 SAEs within four weeks of finishing RT were 9 (6%) LCCRT-OP vs 2 (1%) SCRT-OP. In the TME group, grade ≥3 SAEs occurred in 14 (18%) of 78, with one postoperative death from sepsis after anastomotic leakage and intraperitoneal perforation from anastomotic leak in 12 (15%).
The phase 2 effect (HR 3.7, 1.7-8.0) was far larger than the pooled 12-month estimate (HR 1.90), and the authors ran exploratory post-hoc analyses of stratification variables, tumour length, and centre organ-preservation volume to explain the phase difference. Baseline MRI excluded nodal disease, yet 17 (22%) of TME specimens carried positive nodes, so occult nodal disease is present in the preserved cohort too and is not captured by a 12-month TME-free endpoint. The primary TME comparator in phase 3 was self-selected, not randomised.
TME-free survival at 12 months is an implementation readout, not durable organ preservation: it counts who has avoided surgery so far, not who stays disease-free without it. The clinically load-bearing question, whether the higher cCR rate after 50 Gy/25 fx converts into sustained preservation without a local-recurrence penalty, waits on the 30-month endpoint.
CONSORT flow
Interim 12-month implementation analysis; prespecified 30-month organ-preservation primary endpoint unreported. Phase 3 TME arm by patient preference, not randomisation.
- Does the 12-month TME-free gap hold at the 30-month organ-preservation endpoint n=66 · primary completion 2025-09 · SCRT vs LCRT plus consolidation, organ preservation
- Local recurrence and salvage rates after non-operative management recruiting Nordic ORgan Preservation Pilot Approach Nonrandomised Single-Arm Trial for Non-Operative Management of Rectal Cancer Phase NAn=200 · primary completion 2028-12 · single-arm NOM cohort reporting local regrowth raterecruiting Asian Watch-and-Wait Database (AWWD)n=337 · primary completion 2029-10 · W&W registry after short- or long-course neoadjuvant RT
- Whether a later response assessment would narrow the short-course deficit recruiting Organ Preservation in Rectal Cancer: Contact X-ray Brachytherapy vs Extending the Waiting Interval and Local Excision Phase NAn=168 · primary completion 2025-03 · extends waiting interval after SCRT before response call