{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:26:07Z","timestamp":1788791167289,"version":"build-2803163510"},"reference-count":80,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am Soc Clin Oncol Educ Book"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Immune checkpoint inhibitors (ICIs) have fundamentally transformed the treatment landscape for localized colorectal cancer (CRC), particularly for the mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) subgroups. This review evaluates the current clinical evidence and evolving paradigms of immunotherapy in early-stage CRC. In localized MSI-H colon and rectal cancers, neoadjuvant immunotherapy has demonstrated unprecedented efficacy, yielding near-universal major pathologic responses and high rates of pathologic complete responses. For MSI-H rectal cancer, these deep and sustained clinical complete responses have established nonoperative management as a viable, organ-preserving standard of care for highly selected patients undergoing rigorous multidisciplinary surveillance. Despite these rapid advancements, critical questions remain regarding optimal regimen selection, treatment duration, and the integration of circulating tumor DNA (ctDNA) for molecular residual disease monitoring. Although ctDNA is a promising dynamic biomarker, it currently cannot replace definitive pathologic assessment outside of clinical trials. Furthermore, extending the benefits of immunotherapy to the majority of patients with microsatellite-stable (MSS) CRC represents a significant unmet clinical need. Current evidence for ICIs in localized MSS disease remains limited, although investigational combination strategies incorporating radiation, chemotherapy, and novel immune modulators are yielding hypothesis-generating signals. Future progress hinges on precision de-escalation protocols and biomarker-driven, response-adapted trial designs to validate surrogate end points and optimize patient outcomes across all localized CRC subtypes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/edbk-26-520600","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T19:59:14Z","timestamp":1777665554000},"source":"Crossref","is-referenced-by-count":4,"title":["Immunotherapy in Localized Colorectal Cancer: Current Practice and Future Directions"],"prefix":"10.1200","volume":"46","author":[{"given":"Evelyn Yi Ting","family":"Wong","sequence":"first","affiliation":[{"name":"Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore"},{"name":"University College Hospital, NHS Foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheela R.","family":"Damle","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA"},{"name":"Division of Hematology\/Oncology, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Keen","family":"Shiu","sequence":"additional","affiliation":[{"name":"University College Hospital, NHS Foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey A.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA"},{"name":"Division of Hematology\/Oncology, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4852-4642","authenticated-orcid":true,"given":"Christopher H.","family":"Lieu","sequence":"additional","affiliation":[{"name":"University of Colorado Anschutz Medical Center, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/narcan\/zcad031"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2009.03392.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01351"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2400634"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0805-8"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2404512"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2200075"},{"key":"e_1_3_2_9_2","volume-title":"Presented at the 2025 ASCO Annual Meeting","author":"Sinicrope F-SO FA","year":"2025","unstructured":"Sinicrope F-SO FA, Arnold D, Peters W, et al: Meyerhardt randomized trial of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for patients with stage III deficient DNA mismatch repair (dMMR) colon cancer (Alliance A021502; ATOMIC). Presented at the 2025 ASCO Annual Meeting, 2025"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02583"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-020-02667-4"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.07.011"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.09.004"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.17_suppl.LBA3504"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.4_suppl.158"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03250-w"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.4_suppl.19"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2023.41.4_suppl.108","article-title":"Survival outcomes and functional results of VOLTAGE-A: Preoperative chemoradiotherapy (CRT) and consolidation nivolumab (nivo) in patients (pts) with both microsatellite stable (MSS) and microsatellite instability\u2013high (MSI-H) locally advanced rectal cancer (LARC)","volume":"41","author":"Tsukada Y","year":"2023","unstructured":"Tsukada Y, Bando H, Inamori K, et al: Survival outcomes and functional results of VOLTAGE-A: Preoperative chemoradiotherapy (CRT) and consolidation nivolumab (nivo) in patients (pts) with both microsatellite stable (MSS) and microsatellite instability\u2013high (MSI-H) locally advanced rectal cancer (LARC). J Clin Oncol 41, 2023 (suppl 4; abstr 108)","journal-title":"J Clin Oncol"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.3_suppl.117"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(21)00348-4"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clcc.2024.07.001"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(22)00439-3"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(24)00203-1"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2022.7060"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2022.07.008"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032709"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1713709"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00046"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040694"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clcc.2025.02.003"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.16160"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy218"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2020.153073"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2409154"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2025-CT002"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03254-6"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-25-1242"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz233"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-020-07169-6"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2013.12.005"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.4_suppl.008"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.4_suppl.207"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.4_suppl.158"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.27.1825"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.08.602"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.10.096"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00079-6"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.06.019"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01208"},{"key":"e_1_3_2_50_2","article-title":"Neoadjuvant therapy with mFOLFOXIRI combined with camrelizumab and bevacizumab for microsatellite stable, locally advanced rectal cancer: A single-arm, open-label phase II study","volume":"43","author":"Wang X","year":"2025","unstructured":"Wang X, Huang D, Xie Y, et al: Neoadjuvant therapy with mFOLFOXIRI combined with camrelizumab and bevacizumab for microsatellite stable, locally advanced rectal cancer: A single-arm, open-label phase II study. J Clin Oncol 43, 2025 (suppl 16; abstr e15633)","journal-title":"J Clin Oncol"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.05.250"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2026.44.2_suppl.119"},{"key":"e_1_3_2_53_2","article-title":"PKUCH 04 trial: Total neoadjuvant chemoradiation combined with neoadjuvant PD-1 blockade for pMMR\/MSS locally advanced middle to low rectal cancer","volume":"40","author":"Wu A","year":"2022","unstructured":"Wu A, Li Y, Ji D, et al: PKUCH 04 trial: Total neoadjuvant chemoradiation combined with neoadjuvant PD-1 blockade for pMMR\/MSS locally advanced middle to low rectal cancer. J Clin Oncol 40, 2022 (suppl 16; abstr 3609)","journal-title":"J Clin Oncol"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03360-5"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.07.004"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2021.1683"},{"key":"e_1_3_2_57_2","article-title":"Neoadjuvant chemoradiotherapy plus PD-1 inhibitor (tislelizumab) for high risk and MRF+ low locally advanced rectal cancer","volume":"43","author":"Lin J","year":"2025","unstructured":"Lin J, Zhuang Y, Hu H, et al: Neoadjuvant chemoradiotherapy plus PD-1 inhibitor (tislelizumab) for high risk and MRF+ low locally advanced rectal cancer. J Clin Oncol 43, 2025 (suppl 16; abstr e15644)","journal-title":"J Clin Oncol"},{"key":"e_1_3_2_58_2","first-page":"913","article-title":"[Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: The initial results of a randomized controlled clinical trial (STELLAR II)]","volume":"47","author":"Li HY","year":"2025","unstructured":"Li HY, Zhou HT, Wei LC, et al: [Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: The initial results of a randomized controlled clinical trial (STELLAR II)]. Zhonghua Zhong Liu Za Zhi 47:913-921, 2025","journal-title":"Zhonghua Zhong Liu Za Zhi"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(25)00286-4"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02261"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.06.015"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.04.228"},{"key":"e_1_3_2_63_2","volume-title":"NCCN Guidelines Version 5.2025 Colon Cancer","author":"(NCCN) NCCN","year":"2025","unstructured":"(NCCN) NCCN: NCCN Guidelines Version 5.2025 Colon Cancer. 2025. https:\/\/www.nccn.org"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01889"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09679-4"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2017.01.017"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.2756"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67313"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01762-y"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.16_suppl.e15647"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.16_suppl.3587"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2023.101824"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-025-01018-0"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-024-02730-7"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2026.44.2_suppl.14"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.11.012"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2026.44.2_suppl.TPS258"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-3213"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO-25-01883"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2303269"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.16_suppl.TPS3640"}],"container-title":["American Society of Clinical Oncology Educational Book"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/EDBK-26-520600","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T19:59:19Z","timestamp":1777665559000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/EDBK-26-520600"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":80,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1200\/EDBK-26-520600"],"URL":"https:\/\/doi.org\/10.1200\/edbk-26-520600","relation":{},"ISSN":["1548-8748","1548-8756"],"issn-type":[{"value":"1548-8748","type":"print"},{"value":"1548-8756","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"article-number":"e520600"}}