Impact of Neoadjuvant Immunotherapy in Localized Rectal Cancer. A Systematic Review

Article Article scientifique Revue de la littérature Impact of Neoadjuvant Immunotherapy in Localized Rectal Cancer. A Systematic Review eng 2025-08-26 2025-12 author Salihu Florian Faculty of Medicine, University of Geneva, Geneva, Switzerland. 975232 author Corro Claudia Department of Oncology, Geneva University Hospitals, Geneva, Switzerland; Translational Research Center in Onco-Hematology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Swiss Cancer Center Léman, Geneva and Lausanne, Switzerland. 948048 Département de pathologie et immunologie (PATIM) author Ris Frédéric Department of Visceral Surgery, Geneva University Hospitals, Geneva, Switzerland. 53083 Département de chirurgie (CHIRU) author Meurette Guillaume Department of Visceral Surgery, Geneva University Hospitals, Geneva, Switzerland. 403298 Département de chirurgie (CHIRU) author Durham André Department of Radio-Oncology, Geneva University Hospitals, Geneva, Switzerland. 976635 André-Dante Durham Faivre author Genoud Vassilis Translational Research Center in Onco-Hematology, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 670221 Département de médecine (DEMED) author Bornand Aurélie Department of Pathology, Geneva University Hospitals, Geneva, Switzerland. 658688 author Meyer Jeremy Department of Visceral Surgery, Geneva University Hospitals, Geneva, Switzerland. 715391 author Kossler Thibaud Faculty of Medicine, University of Geneva, Geneva, Switzerland; Department of Oncology, Geneva University Hospitals, Geneva, Switzerland; Translational Research Center in Onco-Hematology, Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address: Thibaud.Kossler@hcuge.ch. 500516 Département de médecine (DEMED) 425-431.e1 10.1016/j.clcc.2025.08.005 40975683 1533-0028 https://www.sciencedirect.com/science/article/pii/S1533002825000738 Current treatments for locally advanced rectal cancer (LARC) include preoperative radiotherapy, chemotherapy and chemoradiotherapy followed by total mesorectal excision (TME), which can severely impact quality of life. Recently, anti-PD1 immunotherapy in microsatellite instability high (MSI-H) LARC has shown 100% clinical complete responses, allowing patients to avoid surgery with minimal toxicity. This review assesses the safety, toxicity, pathological impact, and long-term benefits of incorporating immunotherapy into the neoadjuvant treatment of microsatellite stable (MSS) and MSI-H LARC. This systematic review, conducted following PRISMA guidelines, investigates neoadjuvant immunotherapy in LARC. Data on study characteristics, treatment protocols, and outcomes were extracted. Quality assessment was conducted by using the Methodological Index for nonrandomized studies (MINORS) and the RoB2 tool. Patients were categorized into MSI-H, MSS, and unknown microsatellite status cohorts. We found twelve published studies including 547 patients. In the MSS cohort, postneoadjuvant surgery rates ranged from 57.6% to 100%, with a watch-and-wait approach adopted in up to 27.1% of cases. For MSI-H patients, surgery and watch-and-wait rates varied widely (0%-100%), reflecting heterogeneity in management. R0 resection rates were high across cohorts (70%-100% MSS, 80%-100% MSI-H). Pathological complete response (pCR) rates were 25% to 50% in MSS and 50% to 60% in MSI-H cohorts. Grade 3-4 adverse events ranged from 3.9% to 45.2% (MSS), 0% to 60% (MSI-H), with immune-related events generally below 10%. The role of immunotherapy in MSS rectal cancer remains unclear; phase III trials and translational research are needed urgently for guidance. Clinical complete response Locally advanced rectal cancer MSI-H MSS Humans Rectal Neoplasms / therapy Rectal Neoplasms / pathology Rectal Neoplasms / immunology Rectal Neoplasms / genetics Neoadjuvant Therapy / methods Microsatellite Instability Immunotherapy / methods Immune Checkpoint Inhibitors / therapeutic use Watchful Waiting / statistics & numerical data Treatment Outcome Quality of Life Dewey 616.07 Dewey 616 Dewey 617 137 Département de pathologie et immunologie 21F 56 Département de médecine 221 57 Département de chirurgie 222 false Clinical colorectal cancer 24 4 1638c411-c87f-44e1-a94f-513cdf0b6288 Article (Published version) Public Article.pdf 996897 application/pdf CC BY-4.0 6f68edab89c609d14c224a7f9163f722dae69c4d9724ad2acb7325d20194617c openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département de chirurgie

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Impact of Neoadjuvant Immunotherapy in Localized Rectal Cancer. A Systematic Review	Clinical colorectal cancer			2025	19	321

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Salihu, Florian