Neoadjuvante chemoradiotherapie met of zonder PD-1-remmers bij MMR-proficient rectumcarcinoom: meta-analyse

AIM: In proficient mismatch repair (pMMR) non metastatic rectal cancer, standard neoadjuvant chemoradiotherapy (nCRT) yields low pathological and clinical complete response rates. Early randomized trials suggest adding PD 1 inhibitors may increase response but randomized evidence has not been synthesized. METHODS: We performed a systematic review and meta-analysis of phase II-III randomized trials comparing nCRT plus PD 1 inhibitor versus nCRT alone in adults with untreated pMMR non metastatic rectal cancer. PubMed, Web of Science, Embase and CENTRAL were searched to 30 Sept 2025. Two reviewers extracted data. Dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals (CIs) using a DerSimonian-Laird random effects model; heterogeneity was assessed by I2. Prespecified subgroup analyses compared short course versus long course radiotherapy. RESULTS: Six trials (n=935; nCRT+PD 1 = 461; nCRT=474) were included; agents evaluated included pembrolizumab, sintilimab, tislelizumab and camrelizumab. PD 1 addition significantly increased pathological complete response (pCR) (RR 1.79, 95% CI 1.34-2.40) and showed a non-definitive increase in clinical complete response (cCR) (RR 1.67, 95% CI 0.89-3.13). No clear differences were seen for R0 resection, sphincter preservation, grade ≥3 neoadjuvant toxicity, or surgery related adverse events. Subgroup analysis suggested greater pCR benefit with short course radiotherapy. CONCLUSION: Among patients with pMMR non-metastatic rectal cancer, adding PD-1 inhibitors to standard nCRT improves pCR-most markedly when combined with short-course radiotherapy-with no statistically significant increase detected in high-grade neoadjuvant toxicity or major surgical morbidity. These randomized data support progression to confirmatory phase III trials to define optimal sequencing, regimen standardization and long-term oncologic and functional outcomes.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier 420251137668.