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Background: Immunotherapy has become the first-line treatment for metastatic mismatch repair deficient (dMMR) colorectal cancer. The efficacy and safety of neoadjuvant immunotherapy for the treatment of non-metastatic dMMR colorectal cancer remain unclear. In this article, we explore the clinical effect and safety of neoadjuvant immunotherapy for non-metastatic dMMR colorectal cancer.
Methods: We collected clinical data from the databases (PubMed, Wanfang Embase, Cochrane Library, and China National Knowledge Infrastructure databases) up to November 2024. The primary outcomes of major pathological response (MPR), pathological complete response (pCR), and other outcomes were analyzed for the final results. The secondary outcomes (pCR rates for the subgroups) were also analyzed.
Results: We included 21 articles with 628 non-metastatic dMMR colorectal cancers. A pCR was found in 320/480 (66.6%) patients [effect size (ES): 0.70, 95% CI: 0.66 to 0.74] with the fixed-effects model and little heterogeneity. A MPR was found in 388/452 (85.8%) patients (ES: 0.86, 95% CI: 0.81 to 0.91) with the fixed-effects model and little heterogeneity. In the subgroup analysis, pCR rates were similar in the T1-T3 group and T4a-T4b group in the fixed-effects model with minimal heterogeneity (OR: 0.76, 95% CI: 0.48 to 1.22). The pCR rates were similar in the colon cancer group and rectal cancer group in the fixed-effects model with minimal heterogeneity (OR: 1.41, 95% CI: 0.39 to 5.12). Similar pCR rates were found in the immune monotherapy group and immune therapy plus chemotherapy group (OR: 0.74, 95% CI: 0.26 to 2.10) with the fixed-effects model and little heterogeneity.
Conclusion: Neoadjuvant immunotherapy achieves high rates of pCR and MPR for non-metastatic dMMR colorectal cancer. For locally advanced T4 stage dMMR colorectal cancer, neoadjuvant immunotherapy can still achieve good pCR rates. Neoadjuvant immune monotherapy can achieve good pCRs rates, avoiding the toxic side effects caused by combined dual immunotherapy and chemo(radio)therapy. Neoadjuvant immunotherapy could be another treatment option for non-metastatic dMMR colorectal cancer.
Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024594173.
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http://dx.doi.org/10.3389/fimmu.2025.1540751 | DOI Listing |
Expert Opin Biol Ther
September 2025
Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Introduction: Metastatic colorectal cancer (mCRC) remains a leading cause of cancer mortality worldwide, with limited long-term survival despite therapeutic advances. The increasing understanding of its molecular heterogeneity has paved the way for precision medicine approaches aiming to optimize treatment efficacy and reduce unnecessary toxicity.
Areas Covered: This review provides an in-depth analysis of the current and emerging molecular targets in mCRC, including RAS, BRAF, HER2, and microsatellite instability.
Radiol Med
September 2025
Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134, Florence, Italy.
Purpose: Management of colorectal cancer (CRC) is determined by the stage of the disease and molecular features, such as microsatellite instability (MSI). MSI-high/deficient mismatch repair (MSI-H/dMMR) tumors respond better to immunotherapy but poorly to 5-FU-based treatments. With increasing use of neoadjuvant chemotherapy there is interest in developing non-invasive, radiomics models based on preoperative contrast-enhanced CT scans to predict MSI status and support personalized therapy.
View Article and Find Full Text PDFCrit Rev Oncol Hematol
August 2025
Oncology Unit, ASST Bergamo Est, Seriate, BG, Italy.
Background: Immune checkpoint inhibitors (ICIs) have transformed the management of metastatic mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) colorectal cancer. Their neoadjuvant use in early-stage rectal cancer is an emerging strategy aimed at enhancing tumor response, preserving organ function, and minimizing the morbidity associated with chemoradiotherapy (CRT) and surgery.
Methods: A systematic review was conducted of studies published between January 2000 and April 2025 across PubMed, Embase, Web of Science, and the Cochrane Library.
Front Immunol
August 2025
Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Background: Neoadjuvant immunotherapy has demonstrated satisfactory efficacy for high microsatellite instability/mismatch repair deficiency (dMMR/MSI-H) in locally advanced colorectal cancer (LACRC). This study aims to evaluate the safety and short-term efficacy of neoadjuvant immunotherapy for patients with LACRC.
Methods: We retrospectively analyzed patients with dMMR/MSI-H LACRC who received neoadjuvant immunotherapy at two Chinese medical centers.
J Investig Med High Impact Case Rep
August 2025
Cardinal Bernadin Cancer Center, Loyola University Chicago Stritch School of Medicine Maywood, IL, USA.
Colorectal cancer (CRC) with deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) status represents a highly immunogenic subset that responds well to immune checkpoint inhibitors (ICIs). However, the role of ICIs in resectable, early-stage CRC remains under investigation. We report the case of an 81-year-old woman diagnosed with stage III adenocarcinoma of the right colon, who declined surgery.
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