Efficacy and surgical outcomes of PD-1 inhibitors combined with neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a real-world retrospective cohort study

PD-1 blockade benefits MSI-H/dMMR tumors after prior therapy. Its efficacy as first-line treatment for pMMR/MSS in locally advanced rectal cancer remains unclear. We retrospectively analyzed 84 locally advanced rectal cancer (LARC) patients undergoing total mesorectal excision (TME) (2021–2026). All received neoadjuvant chemoradiotherapy (nCRT) (50.4 Gy, concurrent capecitabine, oxaliplatin plus capecitabine (XELOX)). Patients were divided into Control ( n = 59, nCRT alone) and Combination ( n = 25, nCRT plus PD − 1 inhibitor) groups. Baseline characteristics were balanced ( P > 0.05). The Combination group showed a more favorable TRG distribution than the Control group (Mann-Whitney U test, P = 0.049), with higher pCR rates (32.0% [8/25] vs. 11.9% [7/59], P = 0.041) and no TRG 3 cases (0.0% vs. 8.5%). Sphincter preservation was numerically improved (Dixon rate 84.0% vs. 64.4%, P = 0.116). The combination arm also demonstrated rapid, uniform suppression of serum CEA and CA19-9. Given the retrospective design and limited sample size, these findings should be regarded as preliminary. Adding PD-1 inhibitors to nCRT was associated with higher pCR rates and a more favorable TRG distribution. Sphincter preservation showed a favorable numerical trend (Dixon rate 84.0% vs. 64.4%, P = 0.116). These preliminary results require validation in larger cohorts before informing clinical practice.