Journal: BMC medicine
This publication reports a network meta-analysis of randomized trials in proficient MMR locally advanced rectal cancer, comparing four neoadjuvant strategies:
- Short-course radiotherapy (SCRT)-based regimen alone
- SCRT-based regimen plus immune checkpoint inhibitor
- Long-course chemoradiotherapy (LCRT)-based regimen alone
- LCRT-based regimen plus immune checkpoint inhibitor
Methods:
- Systematic search: Systematic search of major databases up to September 20, 2025
- Inclusion criteria: Randomized controlled trials where ICIs were added to SCRT- or LCRT-based neoadjuvant therapy and compared to the same platform without ICIs
- Analysis: Frequentist random-effects network meta-analysis
- Co-primary endpoints:
- Curative-intent response: Composite of pathologic complete response (pCR) or clinical complete response managed with Watch-and-Wait
- Grade ≥3 treatment-related adverse events (TRAEs)
- Key secondary endpoint: pCR rate
- Treatment ranking: Treatments ranked using SUCRA probabilities
Key results (7 RCTs, 1132 patients):
- Curative-intent response:
- SCRT + ICI had the highest probability of being the most effective regimen (SUCRA 98.5%).
- SCRT + ICI vs SCRT alone: RR 1.82 (95% CI 1.27–2.60).
- SCRT + ICI vs LCRT alone: RR 2.23 (95% CI 1.33–3.76).
- SCRT + ICI vs LCRT + ICI: Numerically better but not statistically significant, RR 1.63 (95% CI 0.88–3.02).
- LCRT + ICI vs LCRT alone: Numerical improvement, RR 1.37 (95% CI 0.98–1.90), not definitively significant.
- pCR:
- Treatment ranking for pCR was consistent with the curative-intent response findings, favoring SCRT + ICI.
- Safety:
- Adding ICIs to either SCRT- or LCRT-based regimens did not significantly increase grade ≥3 TRAEs.
- No significant safety difference between SCRT + ICI and LCRT + ICI (RR 0.87; 95% CI 0.38–2.04).
Clinical implication:
- Among current neoadjuvant platforms for pMMR LARC, SCRT combined with immunotherapy appears to provide the highest likelihood of curative-intent response without a clear trade-off in high-grade toxicity.
- The authors conclude that SCRT is a particularly promising backbone for integration with ICIs and advocate for future phase III trials directly comparing SCRT- versus LCRT-based immunotherapy strategies, with a focus on long-term survival and organ preservation outcomes.