Discordance between radiological and pathological response to neoadjuvant immunotherapy in mismatch...

Mismatch repair deficiency (dMMR) and microsatellite instability (MSI-H) cancers exhibit high immunogenicity and are highly responsive to immune checkpoint inhibitors. In patients with locally advanced dMMR/MSI-H colorectal cancer (CRC), neoadjuvant immunotherapy (NIT) has demonstrated unprecedented pathological complete response (pCR) rates, suggesting nonoperative management strategies may be possible. There remains a discrepancy between radiological assessment and pathological responses to NIT in CRC.

We conducted a systematic review and meta-analysis of studies published between February 2015 and February 2025 to determine if radiological and pathological assessments following neoadjuvant immune checkpoint inhibitor therapy (NIT) were consistent in patients with non-metastatic dMMR/MSI-H CRC. Using PubMed, Embase, and Web of Science, the literature was retrieved, with inclusion criteria focusing on studies that reported both imaging data and pathological results. A random-effects model was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were conducted based on tumor location (colon versus rectum) and type of response (cCR versus pCR).

In 12 studies, 396 patients were included. A total rate of 59.6% discordance was found between radiological and pathological responses. Compared to rectal cancer patients (34.9%), colon cancer patients exhibited a significantly higher rate of discordance (64.2%). A total of 238 patients with confirmed pCR were incorrectly diagnosed as having residual disease on radiological assessment (OR = 61.41; 95% CI: 10.05-375.27;P < 0.00001). A high level of heterogeneity was observed across studies (I2 = 85%), but no publication bias was observed.

In dMMR/MSI-H CRC, radiologic assessment alone cannot reliably assess the efficacy of NIT, particularly in colon cancer. It should be integrated with additional modalities-such as endoscopic evaluation and biomarker analysis-to ensure an accurate appraisal of treatment efficacy.