{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T14:37:10Z","timestamp":1771511830996,"version":"3.50.1"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Our goal was to assess the efficacy of integrating PD-1 inhibitors with total neoadjuvant treatment (iTNT) in enhancing complete response (CR) rates and the propensity for watch-and-wait (WW) strategies in patients with proficient mismatch repair or microsatellite stable (pMMR\/MSS) locally advanced rectal cancer (LARC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective analysis of data prospectively collected was performed. Enrolled patients were divided into Group SCRT-IC, which received short-course radiotherapy (SCRT) followed by six cycles of consolidation immunotherapy with capecitabine and oxaliplatin, or to Group IC-SCRT, which underwent two cycles of induction immunotherapy followed by SCRT and the remaining four cycles of chemotherapy. The primary endpoint was CR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 141 patients were included (72 in Group SCRT-IC and 69 in Group IC-SCRT). At a median follow-up of 29 months, the CR rates were 55.6% in Group SCRT-IC and 53.6% in Group IC-SCRT. The pCR rates were reported at 50% for both groups. Seventeen patients in each group were treated with WW and remained disease-free. The most prevalent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. The cCR rate was a little higher in Group SCRT-IC (56.9% compared to 53.6%), and the incidence of grade 3 to 4 thrombocytopenia was lower in Group SCRT-IC (24.2% vs. 33.9%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>iTNT regimen has significantly improved the CR rate for pMMR\/MSS LARC compared to historical standards, with acceptable toxicity. The approach of prioritizing SCRT followed by immunotherapy is a promising strategy for definitive investigation in future studies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1611386","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T05:23:08Z","timestamp":1750396988000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Total neoadjuvant immunochemotherapy for proficient mismatch repair or microsatellite stable locally advanced rectal 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