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Conventional neoadjuvant chemoradiotherapy (nCRT) demonstrates limited efficacy in achieving disease-free survival (DFS) and organ preservation. Total neoadjuvant therapy (TNT), an emerging paradigm integrating systemic chemotherapy with radiotherapy, aims to address these limitations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To evaluate the short- and long-term oncological outcomes and organ preservation feasibility of TNT in high-risk locally advanced rectal cancer (LARC) patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Designs:<\/jats:title>\n                    <jats:p>A retrospective study was conducted to analyze the short-term and long-term results after total nCRT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>This retrospective study involved 110 rectal cancer patients with high-risk features treated at the Fudan University Shanghai Cancer Center from 2008 to 2022. Patients underwent comprehensive staging and received nCRT followed by either total mesorectal excision (TME) or a watch and wait (W&amp;W) strategy. The regimen included concurrent chemoradiotherapy with 50\u2009Gy\/25 fractions and at least six cycles of induction or consolidation chemotherapy. Both short-term and long-term outcomes were collected and analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Among the LARC patients, 73.6% were stage III, and 47.3% opted for the W&amp;W strategy. The combined rate of clinical complete response or confirmed pathological complete response (pCR) reached 49.1%. During follow-up, 10% of patients experienced local regrowth. The 3-year DFS and overall survival (OS) rates were 75.7% and 92.4%, respectively. The W&amp;W strategy could achieve superior outcomes than patients without pCR in DFS (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.021) and OS (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.006).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>TNT demonstrates durable survival outcomes and facilitates organ preservation in over 50% of high-risk LARC patients. Intensive surveillance is critical for the early detection of local regrowth.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:<\/jats:title>\n                    <jats:p>Our study is retrospective in nature, rather than a prospective clinical trial. Therefore, registration was not conducted, and the Clinical Trial Number is not applicable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17588359251332466","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T08:32:24Z","timestamp":1746779544000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Total neoadjuvant therapy in high-risk rectal cancer: organ preservation and survival outcomes in a single-center retrospective cohort"],"prefix":"10.1177","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3986-7202","authenticated-orcid":false,"given":"Zhiyuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China"},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China"},{"name":"Shanghai Clinical Research Center for 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