Efficacy and Safety of Short-Course Radiotherapy Alone or Combined With Consolidation Chemotherapy Versus Conventional Long-Course Chemoradiotherapy for Locally Advanced Rectal Cancer: A Meta-Analysis of Randomized Controlled Trials.
Chaoyang Wang, Yaguang Han, Shuxin Xue et al.
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In 30 seconds
This meta-analysis of randomized controlled trials compared short-course radiotherapy (SCRT), with or without consolidation chemotherapy, against long-course chemoradiotherapy (LCCRT) for locally advanced rectal cancer. Nine trials involving 3,061 patients were included. Compared with standard LCCRT, SCRT-based total neoadjuvant therapy (TNT) increased pathological complete response (RR = 1.56, 95% CI: 1.24-1.97, P = 0.0002), but also increased grade ≥ 3 acute toxicity. Overall and disease-free survival did not differ significantly. SCRT alone had lower acute toxicity but poorer pathological response and downstaging than LCCRT.
Key findings
- SCRT-based TNT increased pathological complete response versus standard LCCRT (RR = 1.56, 95% CI: 1.24-1.97, P = 0.0002).
- Grade ≥ 3 acute toxicity was higher with SCRT-based TNT (RR = 1.63, 95% CI: 1.14-2.34, P = 0.008).
- SCRT alone was associated with lower pathological complete response (RR = 0.13, 95% CI: 0.03-0.51, P = 0.003) and lower acute toxicity (RR = 0.12, 95% CI: 0.05-0.29, P < 0.00001) than LCCRT.
- SCRT-based TNT showed no significant overall-survival difference (HR = 0.99, 95% CI: 0.76-1.28, P = 0.91) or disease-free-survival difference (HR = 1.05, 95% CI: 0.77-1.43, P = 0.77) versus standard LCCRT.
Why it matters
The findings distinguish SCRT-based TNT from SCRT alone rather than treating short-course regimens as interchangeable. Higher complete-response rates with SCRT-based TNT did not correspond to demonstrated survival benefit and came with more severe acute toxicity, while SCRT alone traded lower toxicity for weaker tumour response. These differences are relevant when weighing neoadjuvant treatment outcomes.
What to keep in mind
The comparison of SCRT-based TNT with LCCRT-based TNT was exploratory and based on a single small trial, leaving that comparison inconclusive.