Background
Phase III RCT (Polish Colorectal Study Group). 312 patients with fixed cT3 or cT4 rectal cancer (not resectable without preoperative treatment). Randomized 1:1 to short-course RT (25 Gy/5 fx) with immediate surgery versus long-course CRT (50.4 Gy + 5-FU/LV) with surgery after 4–6 weeks. Long-term 14-year follow-up published by Bujko 2016; further update by Cisel 2019.
Interventions and follow up
Arm A: Short-course RT 25 Gy in 5 fractions → TME within 7 day
Arm B: Long-course CRT: 50.4 Gy in 28 fractions + 5-FU 325 mg/m² + LV 20 mg/m² days 1–5 and 29–33 → TME 4–6 weeks post-RT
Primary endpoint: Sphincter preservation rate (initially); later OS and late outcome
mFollow up: 14 years (Bujko 2016)
Arm B: Long-course CRT: 50.4 Gy in 28 fractions + 5-FU 325 mg/m² + LV 20 mg/m² days 1–5 and 29–33 → TME 4–6 weeks post-RT
Primary endpoint: Sphincter preservation rate (initially); later OS and late outcome
mFollow up: 14 years (Bujko 2016)
Results
R0 resection: 71% (SCRT) vs 68% (LCCRT), P=.57 — no difference
pCR: 0.7% vs 16.1%, P=.001
Sphincter preservation: 61% vs 58%, P=.57 — no difference
10-yr local recurrence: 22% vs 22%, P=.86 — no difference
10-yr OS: 48% vs 48%, P=.82 — no difference
pCR: 0.7% vs 16.1%, P=.001
Sphincter preservation: 61% vs 58%, P=.57 — no difference
10-yr local recurrence: 22% vs 22%, P=.86 — no difference
10-yr OS: 48% vs 48%, P=.82 — no difference
Adverse events
Main adverse events: Grade ≥3 acute toxicity: LCCRT higher. Late toxicity similar. Similar surgical complication rates.
Conclusions
In fixed/locally advanced rectal cancer, SCRT with immediate surgery and LCCRT with delayed surgery achieved equivalent R0 resection, sphincter preservation, local recurrence, and 10-year OS. LCCRT achieved substantially higher pCR, but this did not translate into better outcomes. Both approaches are valid depending on institutional preference and patient goals.
Key Limitations
Key Limitations: Comparator for "fixed" rectal cancer — many of these patients would now undergo modern TNT (FOLFIRINOX-based neoadjuvant) with much higher pCR rates and potentially better outcomes. SCRT with immediate surgery does not allow downstaging. LCCRT with 5-FU/LV is not the modern standard (capecitabine or TNT preferred). The fact that higher pCR (16% vs 0.7%) did not improve survival challenges pCR as a surrogate endpoint in this population.
Clinical Context
The Polish trial confirmed that local control outcomes with SCRT and LCCRT are equivalent even in locally advanced disease (fixed T3/T4). The remarkable equivalence in outcomes despite the dramatic pCR difference suggests pCR is not a reliable surrogate for survival. Modern TNT strategies (RAPIDO: SCRT + CAPOX → surgery; PRODIGE 23: TNT with FOLFIRINOX + CRT) achieve ~27% pCR with potential survival advantage.
References