Patients with locally advanced rectal cancer who received an immunotherapy drug on top of standard chemoradiotherapy before surgery showed higher rates of a complete pathological response, according to a retrospective cohort study published in BMC Cancer. The finding is preliminary, and the authors themselves caution that larger studies are needed before it can inform clinical practice.
The study analyzed 84 patients with locally advanced rectal cancer who underwent total mesorectal excision between 2021 and 2026. All patients received neoadjuvant chemoradiotherapy consisting of 50.4 Gy of radiation with concurrent capecitabine and oxaliplatin plus capecitabine, a regimen known as XELOX. The cohort was divided into two groups: a control group of 59 patients treated with chemoradiotherapy alone, and a combination group of 25 patients who also received a PD-1 inhibitor.
They have established benefit in tumors with high microsatellite instability or mismatch repair deficiency, but their value as first-line treatment for the more common proficient mismatch repair, microsatellite-stable form of locally advanced rectal cancer has remained unclear. The new study addresses that gap in a real-world setting.
At baseline, the two groups were balanced, with no statistically significant differences in measured characteristics. After neoadjuvant treatment, the combination group showed a more favorable distribution of tumor regression grades, assessed with a Mann-Whitney U test that yielded a P value of 0.049. Notably, no patients in the combination arm had the poorest regression grade, TRG 3, compared with 8.5 percent of controls.
The most striking difference appeared in complete pathological response rates. In the combination group, 32.0 percent of patients, or 8 of 25, achieved a pathological complete response. In the control group, the rate was 11.9 percent, or 7 of 59. This difference was statistically significant, with a P value of 0.041.
Surgical outcomes also showed a favorable trend for the combination group, though the difference did not reach statistical significance. Sphincter-preserving surgery, measured by the Dixon procedure rate, was performed in 84.0 percent of the combination group versus 64.4 percent of controls, with a P value of 0.116. Because this result is numerical rather than statistically confirmed, it should be interpreted with caution.
The study also tracked serum tumor markers. Patients in the combination arm demonstrated rapid and uniform suppression of both carcinoembryonic antigen and CA19-9, two markers commonly monitored in colorectal cancer. The abstract does not report formal statistical comparisons for these marker dynamics.
The authors are explicit about the limitations of their work. The study is retrospective in design, meaning patients were not randomly assigned to treatment groups, and the sample size is limited, particularly in the combination arm of 25 patients. These factors mean the findings should be regarded as preliminary and hypothesis-generating rather than practice-changing.
The conclusion drawn by the researchers is measured: adding PD-1 inhibitors to neoadjuvant chemoradiotherapy was associated with higher pathological complete response rates and a more favorable tumor regression grade distribution, while sphincter preservation showed a favorable numerical trend. They state that these preliminary results require validation in larger cohorts before informing clinical practice.
Subject of Research: PD-1 inhibitor immunotherapy combined with neoadjuvant chemoradiotherapy for locally advanced rectal cancer
Article Title: Efficacy and surgical outcomes of PD-1 inhibitors combined with neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a real-world retrospective cohort study
Article References: Chen, X., Bai, X., Zhao, Y., Gao, M., & Tang, J. (2026). Efficacy and surgical outcomes of PD-1 inhibitors combined with neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a real-world retrospective cohort study. BMC Cancer. https://doi.org/10.1186/s12885-026-17239-w
Image Credits: AI Generated
DOI: 10.1186/s12885-026-17239-w
Keywords: rectal cancer, PD-1 inhibitor, immunotherapy, neoadjuvant chemoradiotherapy, pathological complete response, tumor regression grade, sphincter preservation, retrospective cohort study, microsatellite stability, total mesorectal excision, CEA, CA19-9
News Source: Nathaniel Bowman. (October 29, 2026). Adding PD-1 Inhibitors to Rectal Cancer Therapy Linked to Higher Complete Response Rates. Scienmag.
