{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:59:38Z","timestamp":1791377978200,"version":"4.3.2"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Six months of treatment with dostarlimab followed by nonoperative management in case of clinical complete response (cCR) is the new standard-of-care for patients with microsatellite instability-high (MSI-H)\/mismatch repair deficient (dMMR) locally advanced rectal cancer (LARC). The most recent update of the seminal phase II trial by Cercek et al. shows a cCR rate of 100% that allowed sparing chemoradiation and surgery to all included patients. Here, we present three clinical cases of patients with dMMR and MSI-H LARC treated with neoadjuvant dostarlimab at three Italian institutions with radiological evidence of disease progression while on treatment and discuss potential similarities among them to understand when and how this apparently rare event may occur.<\/jats:p>","DOI":"10.1093\/oncolo\/oyaf394","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T13:04:58Z","timestamp":1764335098000},"source":"Crossref","is-referenced-by-count":4,"title":["Neoadjuvant immunotherapy for dMMR\/MSI-H locally advanced rectal cancer patients: demystifying the 100% clinical complete response paradigm"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7725-3434","authenticated-orcid":false,"given":"Federica","family":"Marmorino","sequence":"first","affiliation":[{"name":"Unit of Medical Oncology, Azienda Ospedaliera Universitaria Pisana , Pisa 56126,","place":["Italy"]},{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa , Pisa 56126,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5306-3596","authenticated-orcid":false,"given":"Federica","family":"Morano","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan 20133,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Anna","family":"Canciello","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Oncology Unit, Universit\u00e0 degli Studi della Campania Luigi Vanvitelli , Naples 80131,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piercarlo","family":"Rossi","sequence":"additional","affiliation":[{"name":"Diagnostic and Interventional Radiology Unit, Azienda Ospedaliero-Universitaria Pisana , Pisa 56126,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalice","family":"Gandini","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino , Genoa 16132,","place":["Italy"]},{"name":"Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Inserm, Universit\u00e9 Paris Cit\u00e9, Personalized Medicine, Phamacogenomics and Therapeutic Optimization , Paris 75006,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8475-5459","authenticated-orcid":false,"given":"Pierre","family":"Laurent-Puig","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Inserm, Universit\u00e9 Paris Cit\u00e9, Personalized Medicine, Phamacogenomics and Therapeutic Optimization , Paris 75006,","place":["France"]},{"name":"Institut du Cancer Paris, Cancer Research for Personalized Medicine, Assistance Publique-H\u00f4pitaux de Paris Centre, H\u00f4pital Europ\u00e9en Georges Pompidou , Paris 75015,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Ugolini","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Molecular Pathology and Critical Area, Unit of Pathology, University Hospital of Pisa , Pisa 56126,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, Oncology Unit, Universit\u00e0 degli Studi della Campania Luigi Vanvitelli , Naples 80131,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0520-4841","authenticated-orcid":false,"given":"Chiara","family":"Cremolini","sequence":"additional","affiliation":[{"name":"Unit of Medical Oncology, Azienda Ospedaliera Universitaria Pisana , Pisa 56126,","place":["Italy"]},{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa , Pisa 56126,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"2025122317580181200_oyaf394-B1","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1056\/NEJMoa2017699","article-title":"Pembrolizumab in microsatellite-instability-high advanced colorectal cancer","volume":"383","author":"Andr\u00e9","year":"2020","journal-title":"N Engl J Med"},{"key":"2025122317580181200_oyaf394-B2","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1056\/NEJMoa2402141","article-title":"Nivolumab plus ipilimumab in microsatellite-instability\u2013high metastatic colorectal cancer","volume":"391","author":"Andre","year":"2024","journal-title":"N Engl J Med"},{"key":"2025122317580181200_oyaf394-B3","doi-asserted-by":"crossref","first-page":"1626438","DOI":"10.3389\/fimmu.2025.1626438","article-title":"The efficacy and safety of neoadjuvant and adjuvant chemo(radio)therapy combined with surgery in patients with locally advanced rectal cancer harboring defective mismatch repair system: a large-scale multicenter propensity score analysis","volume":"16","author":"Wang","year":"2025","journal-title":"Front Immunol"},{"key":"2025122317580181200_oyaf394-B4","doi-asserted-by":"crossref","first-page":"3271","DOI":"10.1158\/1078-0432.CCR-19-3728","article-title":"Mismatch repair deficient rectal cancer and resistance to neoadjuvant chemotherapy","volume":"26","author":"Cercek","year":"2020","journal-title":"Clin Cancer Res"},{"key":"2025122317580181200_oyaf394-B5","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1056\/NEJMoa2201445","article-title":"PD-1 blockade in mismatch repair\u2013deficient, locally advanced rectal cancer","volume":"386","author":"Cercek","year":"2022","journal-title":"N Engl J Med"},{"key":"2025122317580181200_oyaf394-B6","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1056\/NEJMoa2404512","article-title":"Nonoperative management of mismatch repair-deficient tumors","volume":"392","author":"Cercek","year":"2025","journal-title":"N Engl J Med"},{"key":"2025122317580181200_oyaf394-B7","doi-asserted-by":"crossref","first-page":"3771","DOI":"10.1158\/1078-0432.CCR-22-3964","article-title":"Transcriptomic signatures of MSI-high metastatic colorectal cancer predict efficacy of immune checkpoint inhibitors","volume":"29","author":"Gallois","year":"2023","journal-title":"Clin Cancer Res"},{"key":"2025122317580181200_oyaf394-B8","doi-asserted-by":"crossref","first-page":"103929","DOI":"10.1016\/j.esmoop.2024.103929","article-title":"Curative immune checkpoint inhibitors therapy in patients with mismatch repair-deficient locally advanced rectal cancer: a real-world 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Oncol"},{"key":"2025122317580181200_oyaf394-B16","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1158\/2159-8290.CD-19-1416","article-title":"Inactivation of Fbxw7 impairs dsRNA sensing and confers resistance to PD-1 blockade","volume":"10","author":"Gstalder","year":"2020","journal-title":"Cancer Discov"},{"key":"2025122317580181200_oyaf394-B17","first-page":"e240","article-title":"Mucinous adenocarcinoma predicts poor response and prognosis in patients with locally advanced rectal cancer: a pooled analysis of individual participant data from 3 prospective studies","volume":"20","author":"Zhang","year":"2021","journal-title":"Clin Colorectal Cancer"},{"key":"2025122317580181200_oyaf394-B18","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/bjs\/znac050","article-title":"Pathological response following neoadjuvant immunotherapy in mismatch repair-deficient\/microsatellite instability-high locally advanced, non-metastatic colorectal cancer: neoadjuvant 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