{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T20:17:21Z","timestamp":1778530641700,"version":"3.51.4"},"reference-count":90,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Advances in surgical techniques, radiographic imaging capabilities, radiotherapy, and chemotherapy have led to improved outcomes for patients with rectal adenocarcinoma. Treatment strategies have correspondingly evolved, as seen with total neoadjuvant therapy (TNT) and organ preservation approaches. TNT is a treatment strategy for primary, non-metastatic, resectable mismatch repair proficient rectal cancer where the intent is to administer all appropriate adjuvant therapy in the preoperative phase, including both systemic therapy and chemoradiotherapy\/radiotherapy. In this setting, TNT is increasingly administered for the purposes of maximizing tumour response to facilitate resection, improving treatment compliance, thus increasing the likelihood of a complete response to allow for organ preservation and for the possibility of improving survival. While several recent randomized controlled trials have described the role of TNT in the contemporary treatment of rectal cancer, there is significant heterogeneity in sequencing of treatments, dosing, allowance for non-operative management, and the potential for over-treatment. Our objective here was to incorporate current evidence to develop a consensus-based institutional treatment algorithm to be used in the ambulatory and multidisciplinary team setting for the treatment of stage I\u2013III rectal cancer.<\/jats:p>","DOI":"10.3390\/curroncol33050274","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T19:35:43Z","timestamp":1778528143000},"page":"274","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Consensus Approach to the Incorporation of Total Neoadjuvant Therapy in a Treatment Algorithm for Stage I\u2013III Resectable Rectal Cancer"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2090-8994","authenticated-orcid":false,"given":"Sami A.","family":"Chadi","sequence":"first","affiliation":[{"name":"Sprott Department of Surgery, Division of General Surgery and Surgical Oncology, University Health Network and Princess Margaret Cancer Centre, Toronto, ON M5G 2C4, Canada"},{"name":"Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9934-2443","authenticated-orcid":false,"given":"Karineh","family":"Kazazian","sequence":"additional","affiliation":[{"name":"Sprott Department of Surgery, Division of General Surgery and Surgical Oncology, University Health Network and Princess Margaret Cancer Centre, Toronto, ON M5G 2C4, Canada"},{"name":"Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2881-6717","authenticated-orcid":false,"given":"Paul","family":"Savage","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4818-318X","authenticated-orcid":false,"given":"Christine","family":"Brezden-Masley","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada"},{"name":"Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5956-3623","authenticated-orcid":false,"given":"Ron","family":"Burkes","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada"},{"name":"Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada"},{"name":"Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anand","family":"Govindarajan","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada"},{"name":"Department of Surgery, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Hosni","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada"},{"name":"Department of Radiation Oncology, University of Toronto, Toronto, ON M5T 1P5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada"},{"name":"Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada"},{"name":"Department of Surgery, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada"},{"name":"Department of Radiation Oncology, University of Toronto, Toronto, ON M5T 1P5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelena","family":"Lukovic","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada"},{"name":"Department of Radiation Oncology, University of Toronto, Toronto, ON M5T 1P5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8327-794X","authenticated-orcid":false,"given":"Aruz","family":"Mesci","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada"},{"name":"Department of Radiation Oncology, University of Toronto, Toronto, ON M5T 1P5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Sprott Department of Surgery, Division of General Surgery and Surgical Oncology, University Health Network and Princess Margaret Cancer Centre, Toronto, ON M5G 2C4, Canada"},{"name":"Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1441-8777","authenticated-orcid":false,"given":"Fayez","family":"Quereshy","sequence":"additional","affiliation":[{"name":"Sprott Department of Surgery, Division of General Surgery and Surgical Oncology, University Health Network and Princess Margaret Cancer Centre, Toronto, ON M5G 2C4, Canada"},{"name":"Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4420-0958","authenticated-orcid":false,"given":"Abdulazeez","family":"Salawu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada"},{"name":"Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2034-6725","authenticated-orcid":false,"given":"Peter K.","family":"Stotland","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada"},{"name":"Department of Surgery, North York General Hospital, Toronto, ON M2K 1E1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol J.","family":"Swallow","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada"},{"name":"Department of Surgery, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1056\/NEJMoa040694","article-title":"Preoperative versus Postoperative Chemoradiotherapy for Rectal Cancer","volume":"351","author":"Sauer","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S1470-2045(14)71199-4","article-title":"Adjuvant Chemotherapy after Preoperative (Chemo)Radiotherapy and Surgery for Patients with Rectal Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data","volume":"16","author":"Breugom","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/jnci\/80.1.21","article-title":"Postoperative Adjuvant Chemotherapy or Radiation Therapy for Rectal Cancer: Results from NSABP Protocol R-0112","volume":"80","author":"Fisher","year":"1988","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_4","unstructured":"(2023, July 11). Colorectal Cancer Survival Rates|Colorectal Cancer Prognosis. Available online: https:\/\/www.cancer.org\/cancer\/types\/colon-rectal-cancer\/detection-diagnosis-staging\/survival-rates.html."},{"key":"ref_5","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":"ref_6","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1007\/s00268-019-05060-5","article-title":"Compliance to Adjuvant Chemotherapy of Patients Who Underwent Surgery for Rectal Cancer: Report from a Multi-Institutional Research Network","volume":"43","author":"Mari","year":"2019","journal-title":"World J. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1097\/DCR.0000000000000545","article-title":"Quality of Life and Timing of Stoma Closure in Patients with Rectal Cancer Undergoing Low Anterior Resection with Diverting Stoma: A Multicenter Longitudinal Observational Study","volume":"59","author":"Herrle","year":"2016","journal-title":"Dis. Colon Rectum"},{"key":"ref_8","unstructured":"Benson, A.B. (2026). NCCN Clinical Practice Guidelines in Oncology: Rectal Cancer Version 2.2026, National Comprehensive Cancer Network."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.annonc.2025.05.528","article-title":"Localised Rectal Cancer: ESMO Clinical Practice Guideline for Diagnosis, Treatment and Follow-Up","volume":"36","author":"Hofheinz","year":"2025","journal-title":"Ann. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1097\/COC.0000000000000149","article-title":"Complete Neoadjuvant Treatment for Rectal Cancer: The Brown University Oncology Group CONTRE Study","volume":"40","author":"Perez","year":"2017","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/S1470-2045(15)00004-2","article-title":"Effect of Adding mFOLFOX6 after Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer: A Multicentre, Phase 2 Trial","volume":"16","author":"Chow","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e180071","DOI":"10.1001\/jamaoncol.2018.0071","article-title":"Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer","volume":"4","author":"Cercek","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1097\/SLA.0000000000003471","article-title":"Total Neoadjuvant Therapy in Rectal Cancer: A Systematic Review and Meta-Analysis of Treatment Outcomes","volume":"271","author":"Petrelli","year":"2020","journal-title":"Ann. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/S1470-2045(21)00079-6","article-title":"Neoadjuvant Chemotherapy with FOLFIRINOX and Preoperative Chemoradiotherapy for Patients with Locally Advanced Rectal Cancer (UNICANCER-PRODIGE 23): A Multicentre, Randomised, Open-Label, Phase 3 Trial","volume":"22","author":"Conroy","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S1470-2045(20)30555-6","article-title":"Short-Course Radiotherapy Followed by Chemotherapy before Total Mesorectal Excision (TME) versus Preoperative Chemoradiotherapy, TME, and Optional Adjuvant Chemotherapy in Locally Advanced Rectal Cancer (RAPIDO): A Randomised, Open-Label, Phase 3 Trial","volume":"22","author":"Bahadoer","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.annonc.2024.06.019","article-title":"Total Neoadjuvant Therapy with mFOLFIRINOX versus Preoperative Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer: Long-Term Results of the UNICANCER-PRODIGE 23 Trial","volume":"35","author":"Conroy","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ejca.2023.03.021","article-title":"Neoadjuvant Chemotherapy with FOLFIRINOX and Preoperative Chemoradiotherapy for Patients with Locally Advanced Rectal Cancer (UNICANCER PRODIGE 23): Health-Related Quality of Life Longitudinal Analysis","volume":"186","author":"Gourgou","year":"2023","journal-title":"Eur. J. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Socha, J., and Bujko, K. (2023). Does the Gain of Total Neoadjuvant Therapy Outweigh the Harm in Rectal Cancer? Importance of the ATRESS (neoAdjuvant Therapy-RElated Shortening of Survival) Phenomenon: A Systematic Review. Cancers, 15.","DOI":"10.3390\/cancers15041016"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e766","DOI":"10.1097\/SLA.0000000000005799","article-title":"Locoregional Failure During and After Short-Course Radiotherapy Followed by Chemotherapy and Surgery Compared to Long-Course Chemoradiotherapy and Surgery\u2014A Five-Year Follow-up of the RAPIDO Trial","volume":"278","author":"Dijkstra","year":"2023","journal-title":"Ann. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.radonc.2022.04.013","article-title":"Quality of Life and Late Toxicity after Short-Course Radiotherapy Followed by Chemotherapy or Chemoradiotherapy for Locally Advanced Rectal Cancer\u2014The RAPIDO Trial","volume":"171","author":"Dijkstra","year":"2022","journal-title":"Radiother. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1200\/JCO.21.01667","article-title":"Multicenter, Randomized, Phase III Trial of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in Locally Advanced Rectal Cancer (STELLAR)","volume":"40","author":"Jin","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ijrobp.2024.12.035","article-title":"Quality of Life and Functional Outcomes in Patients With Locally Advanced Rectal Cancer Receiving Total Neoadjuvant Therapy Versus Concurrent Chemoradiation Therapy: An Analysis of the STELLAR Trial","volume":"122","author":"Ma","year":"2025","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.1200\/JCO.19.00308","article-title":"Randomized Phase II Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: CAO\/ARO\/AIO-12","volume":"37","author":"Fokas","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e215445","DOI":"10.1001\/jamaoncol.2021.5445","article-title":"Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Patients With Locally Advanced Rectal Cancer: Long-Term Results of the CAO\/ARO\/AIO-12 Randomized Clinical Trial","volume":"8","author":"Fokas","year":"2022","journal-title":"JAMA Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"104483","DOI":"10.1016\/j.esmoop.2025.104483","article-title":"Chemotherapy before or after Preoperative Chemoradiotherapy and Surgery for Locally Advanced Rectal Cancer: 5-Year Results of the CAO\/ARO\/AIO-12 Trial\u2014A General Pairwise Comparison","volume":"10","author":"Diefenhardt","year":"2025","journal-title":"ESMO Open"},{"key":"ref_26","first-page":"388","article-title":"Morbidity and Mortality Following Abdominoperineal Resection for Low Rectal Adenocarcinoma","volume":"53","author":"Vega","year":"2001","journal-title":"Rev. Investig. Clin."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1046\/j.1365-2168.1998.00530.x","article-title":"Radical and Nerve-Preserving Surgery for Rectal Cancer in The Netherlands: A Prospective Study on Morbidity and Functional Outcome","volume":"85","author":"Maas","year":"1998","journal-title":"Br. J. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1046\/j.1365-2168.2000.01357.x","article-title":"Bladder and Sexual Dysfunction after Mesorectal Excision for Rectal Cancer","volume":"87","author":"Nesbakken","year":"2000","journal-title":"Br. J. Surg."},{"key":"ref_29","first-page":"711\u2013717; discussion 717-718","article-title":"Operative versus Nonoperative Treatment for Stage 0 Distal Rectal Cancer Following Chemoradiation Therapy: Long-Term Results","volume":"240","author":"Perez","year":"2004","journal-title":"Ann. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4633","DOI":"10.1200\/JCO.2011.37.7176","article-title":"Wait-and-See Policy for Clinical Complete Responders after Chemoradiation for Rectal Cancer","volume":"29","author":"Maas","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1016\/S0140-6736(18)31078-X","article-title":"Long-Term Outcomes of Clinical Complete Responders after Neoadjuvant Treatment for Rectal Cancer in the International Watch & Wait Database (IWWD): An International Multicentre Registry Study","volume":"391","author":"Hilling","year":"2018","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"44857","DOI":"10.18632\/oncotarget.8622","article-title":"Wait-and-See Treatment Strategies for Rectal Cancer Patients with Clinical Complete Response after Neoadjuvant Chemoradiotherapy: A Systematic Review and Meta-Analysis","volume":"7","author":"Li","year":"2016","journal-title":"Oncotarget"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4008","DOI":"10.1200\/JCO.2020.38.15_suppl.4008","article-title":"Preliminary Results of the Organ Preservation of Rectal Adenocarcinoma (OPRA) Trial","volume":"38","author":"Patil","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1200\/JCO.23.01208","article-title":"Long-Term Results of Organ Preservation in Patients with Rectal Adenocarcinoma Treated with Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial","volume":"42","author":"Verheij","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e2350903","DOI":"10.1001\/jamanetworkopen.2023.50903","article-title":"Organ Preservation and Survival by Clinical Response Grade in Patients With Rectal Cancer Treated With Total Neoadjuvant Therapy: A Secondary Analysis of the OPRA Randomized Clinical Trial","volume":"7","author":"Thompson","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1097\/DCR.0000000000003209","article-title":"An International Expert-Based Consensus on the Definition of a Clinical Near-Complete Response After Neoadjuvant (Chemo)Radiotherapy for Rectal Cancer","volume":"67","author":"Custers","year":"2024","journal-title":"Dis. Colon Rectum"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1200\/JCO.24.00405","article-title":"Risks of Organ Preservation in Rectal Cancer: Data from Two International Registries on Rectal Cancer","volume":"43","author":"Fernandez","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1097\/DCR.0000000000002930","article-title":"Local Regrowth and the Risk of Distant Metastases Among Patients Undergoing Watch-and-Wait for Rectal Cancer: What Is the Best Control Group? Multicenter Retrospective Study","volume":"67","author":"Vailati","year":"2024","journal-title":"Dis. Colon Rectum"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1097\/DCR.0000000000003941","article-title":"Risk of Distant Metastasis After Total Neoadjuvant Therapy: Local Regrowth Versus Surgery After Total Neoadjuvant Therapy with Pathologic Near-Complete Response in Rectal Cancer","volume":"68","author":"Karahan","year":"2025","journal-title":"Dis. Colon Rectum"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1200\/JCO.22.00032","article-title":"Organ Preservation in Patients with Rectal Adenocarcinoma Treated with Total Neoadjuvant Therapy","volume":"40","author":"Patil","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1001\/jamaoncol.2019.0186","article-title":"Safety and Feasibility of Using Magnetic Resonance Imaging Criteria to Identify Patients with \u201cGood Prognosis\u201d Rectal Cancer Eligible for Primary Surgery: The Phase 2 Nonrandomized QuickSilver Clinical Trial","volume":"5","author":"Kennedy","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1200\/JCO.2012.45.3258","article-title":"Preoperative Magnetic Resonance Imaging Assessment of Circumferential Resection Margin Predicts Disease-Free Survival and Local Recurrence: 5-Year Follow-Up Results of the MERCURY Study","volume":"32","author":"Taylor","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.ijrobp.2009.03.010","article-title":"Late Side Effects and Quality of Life after Radiotherapy for Rectal Cancer","volume":"76","author":"Bruheim","year":"2010","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6199","DOI":"10.1200\/JCO.2005.14.779","article-title":"Late Side Effects of Short-Course Preoperative Radiotherapy Combined with Total Mesorectal Excision for Rectal Cancer: Increased Bowel Dysfunction in Irradiated Patients\u2014A Dutch Colorectal Cancer Group Study","volume":"23","author":"Peeters","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/S1470-2045(13)70599-0","article-title":"Fluorouracil-Based Adjuvant Chemotherapy after Preoperative Chemoradiotherapy in Rectal Cancer: Long-Term Results of the EORTC 22921 Randomised Study","volume":"15","author":"Bosset","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3111","DOI":"10.1200\/JCO.19.00016","article-title":"Oxaliplatin-Based Adjuvant Chemotherapy for Rectal Cancer After Preoperative Chemoradiotherapy (ADORE): Long-Term Results of a Randomized Controlled Trial","volume":"37","author":"Hong","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.4240\/wjgs.v13.i9.1000","article-title":"Evaluating the Benefit of Adjuvant Chemotherapy in Patients with ypT0-1 Rectal Cancer Treated with Preoperative Chemoradiotherapy","volume":"13","author":"Jeon","year":"2021","journal-title":"World J. Gastrointest. Surg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.radonc.2014.10.006","article-title":"No Benefit of Adjuvant Fluorouracil Leucovorin Chemotherapy after Neoadjuvant Chemoradiotherapy in Locally Advanced Cancer of the Rectum (LARC): Long Term Results of a Randomized Trial (I-CNR-RT)","volume":"113","author":"Sainato","year":"2014","journal-title":"Radiother. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1093\/annonc\/mdu560","article-title":"Adjuvant Chemotherapy for Rectal Cancer Patients Treated with Preoperative (Chemo)Radiotherapy and Total Mesorectal Excision: A Dutch Colorectal Cancer Group (DCCG) Randomized Phase III Trial","volume":"26","author":"Breugom","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1093\/annonc\/mdu147","article-title":"Chronicle: Results of a Randomised Phase III Trial in Locally Advanced Rectal Cancer after Neoadjuvant Chemoradiation Randomising Postoperative Adjuvant Capecitabine plus Oxaliplatin (XELOX) versus Control","volume":"25","author":"Counsell","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1001\/jama.294.20.2587","article-title":"Risk of Pelvic Fractures in Older Women Following Pelvic Irradiation","volume":"294","author":"Baxter","year":"2005","journal-title":"JAMA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.radonc.2013.05.009","article-title":"Gender Affects Acute Organ Toxicity during Radiochemotherapy for Rectal Cancer: Long-Term Results of the German CAO\/ARO\/AIO-94 Phase III Trial","volume":"108","author":"Wolff","year":"2013","journal-title":"Radiother. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.ijrobp.2018.12.005","article-title":"Functional Outcomes and Health-Related Quality of Life After Curative Treatment for Rectal Cancer: A Population-Level Study in England","volume":"103","author":"Downing","year":"2019","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1245\/s10434-012-2827-z","article-title":"Effect of Preoperative Radio(Chemo)Therapy on Long-Term Functional Outcome in Rectal Cancer Patients: A Systematic Review and Meta-Analysis","volume":"20","author":"Loos","year":"2013","journal-title":"Ann. Surg. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1056\/NEJMoa2303269","article-title":"Preoperative Treatment of Locally Advanced Rectal Cancer","volume":"389","author":"Schrag","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3724","DOI":"10.1200\/JCO.23.00903","article-title":"Patient-Reported Outcomes During and After Treatment for Locally Advanced Rectal Cancer in the PROSPECT Trial (Alliance N1048)","volume":"41","author":"Basch","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1097\/SLA.0000000000005780","article-title":"Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Initial Results of a Phase III Trial","volume":"277","author":"Mei","year":"2023","journal-title":"Ann. Surg."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1200\/JCO-25-00731","article-title":"Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Final Results of a Phase III Trial","volume":"44","author":"Mei","year":"2026","journal-title":"J. Clin. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S0360-3016(02)02945-0","article-title":"Impact of T and N Substage on Survival and Disease Relapse in Adjuvant Rectal Cancer: A Pooled Analysis","volume":"54","author":"Gunderson","year":"2002","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/s003840100309","article-title":"The Prognostic Inhomogeneity in pT3 Rectal Carcinomas","volume":"16","author":"Merkel","year":"2001","journal-title":"Int. J. Color. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ejca.2018.07.131","article-title":"A Meta-Analysis Assessing the Survival Implications of Subclassifying T3 Rectal Tumours","volume":"104","author":"Siddiqui","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1097\/SLA.0b013e31820b8d52","article-title":"Preoperative High-Resolution Magnetic Resonance Imaging Can Identify Good Prognosis Stage I, II, and III Rectal Cancer Best Managed by Surgery Alone: A Prospective, Multicenter, European Study","volume":"253","author":"Taylor","year":"2011","journal-title":"Ann. Surg."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"MERCURY Study Group (2006). Diagnostic Accuracy of Preoperative Magnetic Resonance Imaging in Predicting Curative Resection of Rectal Cancer: Prospective Observational Study. BMJ, 333, 779.","DOI":"10.1136\/bmj.38937.646400.55"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/bjs.5917","article-title":"Prognostic Significance of Magnetic Resonance Imaging-Detected Extramural Vascular Invasion in Rectal Cancer","volume":"95","author":"Smith","year":"2008","journal-title":"Br. J. Surg."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/0140-6736(90)92631-Q","article-title":"Extent of Mesorectal Spread and Involvement of Lateral Resection Margin as Prognostic Factors after Surgery for Rectal Cancer","volume":"335","author":"Cawthorn","year":"1990","journal-title":"Lancet"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1007\/DCR.0b013e3181a0a37e","article-title":"Magnetic Resonance Imaging Prediction of an Involved Surgical Resection Margin in Low Rectal Cancer","volume":"52","author":"Salerno","year":"2009","journal-title":"Dis. Colon Rectum"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1038\/sj.bjc.6602492","article-title":"Intensified Concurrent Chemoradiotherapy with 5-Fluorouracil and Irinotecan as Neoadjuvant Treatment in Patients with Locally Advanced Rectal Cancer","volume":"92","author":"Klautke","year":"2005","journal-title":"Br. J. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Alvarez, J.A., Shi, Q., Dasari, A., Garcia-Aguilar, J., Sanoff, H., George, T.J., Hong, T., Yothers, G., Philip, P., and Nelson, G. (2024). Alliance A022104\/NRG-GI010: The Janus Rectal Cancer Trial: A Randomized Phase II\/III Trial Testing the Efficacy of Triplet versus Doublet Chemotherapy Regarding Clinical Complete Response and Disease-Free Survival in Patients with Locally Advanced Rectal Cancer. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12529-7"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.ejso.2020.07.033","article-title":"Management of the Positive Pathologic Circumferential Resection Margin in Rectal Cancer: A National Cancer Database (NCDB) Study","volume":"47","author":"Augestad","year":"2021","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1200\/JCO.2014.60.1054","article-title":"Advances and Challenges in Treatment of Locally Advanced Rectal Cancer","volume":"33","author":"Smith","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/S0140-6736(94)92206-3","article-title":"Role of Circumferential Margin Involvement in the Local Recurrence of Rectal Cancer","volume":"344","author":"Adam","year":"1994","journal-title":"Lancet"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1245\/s10434-015-5017-y","article-title":"Predictors of Pathologic Complete Response Following Neoadjuvant Chemoradiotherapy for Rectal Cancer","volume":"23","author":"Attwood","year":"2016","journal-title":"Ann. Surg. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/S2468-1253(18)30301-7","article-title":"Factors Affecting Local Regrowth after Watch and Wait for Patients with a Clinical Complete Response Following Chemoradiotherapy in Rectal Cancer (InterCoRe Consortium): An Individual Participant Data Meta-Analysis","volume":"3","author":"Chadi","year":"2018","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/S2468-1253(18)30309-1","article-title":"Watch and Wait in Rectal Cancer: Is It Time to Subclassify cT3?","volume":"3","year":"2018","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1097\/DCR.0000000000002555","article-title":"Impact of Total Neoadjuvant Therapy on Postoperative Outcomes After Proctectomy for Rectal Cancer","volume":"66","author":"Xu","year":"2023","journal-title":"Dis. Colon Rectum"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1200\/JCO.2016.67.6049","article-title":"Effect of Interval (7 or 11 Weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6)","volume":"34","author":"Lefevre","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1097\/SLA.0000000000003530","article-title":"Does A Longer Waiting Period After Neoadjuvant Radio-Chemotherapy Improve the Oncological Prognosis of Rectal Cancer?: Three Years\u2019 Follow-up Results of the Greccar-6 Randomized Multicenter Trial","volume":"270","author":"Mineur","year":"2019","journal-title":"Ann. Surg."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1200\/JCO.22.00184","article-title":"Neoadjuvant Chemotherapy, Excision, and Observation for Early Rectal Cancer: The Phase II NEO Trial (CCTG CO.28) Primary End Point Results","volume":"41","author":"Kennecke","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S2468-1253(19)30410-8","article-title":"Organ Preservation with Chemoradiotherapy plus Local Excision for Rectal Cancer: 5-Year Results of the GRECCAR 2 Randomised Trial","volume":"5","author":"Rullier","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1001\/jamasurg.2025.1398","article-title":"Chemoradiotherapy and Local Excision vs Total Mesorectal Excision in T2-T3ab, N0, M0 Rectal Cancer: The TAUTEM Randomized Clinical Trial","volume":"160","author":"Pericay","year":"2025","journal-title":"JAMA Surg."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.annonc.2024.10.827","article-title":"A Phase III Randomised Trial on the Addition of a Contact X-Ray Brachytherapy Boost to Standard Neoadjuvant Chemo-Radiotherapy for Organ Preservation in Early Rectal Adenocarcinoma: 5 Year Results of the OPERA Trial","volume":"36","author":"Baron","year":"2025","journal-title":"Ann. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Habr-Gama, A., S\u00e3o Juli\u00e3o, G.P., Ortega, C.D., Vailati, B.B., Araujo, S., Jorge, T., Sabbaga, J., Rossi, G.L., D\u2019Alpino, R., and Kater, F.R. (2023). A Multi-Centre Randomized Controlled Trial Investigating Consolidation Chemotherapy with and without Oxaliplatin in Distal Rectal Cancer and Watch & Wait. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-10984-2"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"TPS3646","DOI":"10.1200\/JCO.2024.42.16_suppl.TPS3646","article-title":"The NEO-RT Trial: A Phase 3 Randomized Trial of Neoadjuvant Chemotherapy, Excision and Observation versus Chemoradiotherapy for Early Rectal Cancer, CCTG CO.32","volume":"42","author":"Kennecke","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"346ra92","DOI":"10.1126\/scitranslmed.aaf6219","article-title":"Circulating Tumor DNA Analysis Detects Minimal Residual Disease and Predicts Recurrence in Patients with Stage II Colon Cancer","volume":"8","author":"Tie","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1001\/jamaoncol.2019.0528","article-title":"Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients with Stages I to III Colorectal Cancer","volume":"5","author":"Reinert","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1056\/NEJMoa2200075","article-title":"Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer","volume":"386","author":"Tie","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1136\/gutjnl-2017-315852","article-title":"Serial Circulating Tumour DNA Analysis during Multimodality Treatment of Locally Advanced Rectal Cancer: A Prospective Biomarker Study","volume":"68","author":"Tie","year":"2019","journal-title":"Gut"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1158\/1078-0432.CCR-20-2299","article-title":"Serial Circulating Tumor DNA in Predicting and Monitoring the Effect of Neoadjuvant Chemoradiotherapy in Patients with Rectal Cancer: A Prospective Multicenter Study","volume":"27","author":"Zhou","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/SLA.0000000000006948","article-title":"Molecular Residual Disease and Recurrence in Rectal Cancer Patients Undergoing Upfront Surgery: A Prospective Cohort Study","volume":"283","author":"Ando","year":"2026","journal-title":"Ann. Surg."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1158\/1078-0432.CCR-25-3774","article-title":"Dynamic ctDNA Monitoring Guides Early Treatment Intensification in Locally Advanced Rectal Cancer Undergoing Neoadjuvant Chemotherapy","volume":"32","author":"Shen","year":"2026","journal-title":"Clin. Cancer Res."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/5\/274\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T20:03:46Z","timestamp":1778529826000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/5\/274"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":90,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["curroncol33050274"],"URL":"https:\/\/doi.org\/10.3390\/curroncol33050274","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]}}}