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In the whole group, median recurrence\u2010free survival was 19.4 months and median distant metastasis\u2010free survival (mDMFS) was 21.9 months. In patients with a pathological complete response (pCR)\/near\u2010pCR median recurrence\u2010free survival (RFS) and distant metastasis\u2010free survival (DMFS) were significantly longer than in patients with minor pathological response with hazard ratio (HR)\u00a0=\u00a00.37 (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.005) for RFS and HR\u00a0=\u00a00.33 (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.002) for DMFS. After median follow\u2010up of 52.5 months, median progression\u2010free survival since BRAFi\/MEKi therapy initiation was 25.1 months. The median time\u2010to\u2010treatment\u2010failure since initiation of neoadjuvant therapy was 22.2 months and was significantly longer in patients with pCR\/near\u2010pCR (HR\u00a0=\u00a00.45; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.022). Neoadjuvant therapy did not result in any new specific complications of surgery. After 48 months, RFS and overall survival were 36.3% and 64.8% or 20% and 37.4% in patients with pCR\/near\u2010pCR and pathological partial response\/pathological nonresponse, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The authors confirmed that BRAFi\/MEKi combination is an effective and safe regimen in the perioperative treatment of stage III\/IV melanoma. Major pathological response to neoadjuvant treatment is a surrogate marker of recurrence including DMFS in these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>\n<jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Our study presents a large comprehensive analysis of neoadjuvant\u2010adjuvant systemic therapy in patients diagnosed with marginally resectable stage III or IV melanoma.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Neoadjuvant therapy effectively reduced the volume of the disease, which facilitated subsequent surgical resection.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>After median follow\u2010up of 52.5 months, median progression\u2010free survival since therapy initiation was 25.1 months. Twelve patients had complete pathological response and 10 patients had a near\u2010complete pathological response\u2014and together they had median recurrence\u2010free survival and distant metastasis\u2010free survival significantly longer than in patients with pathological partial response or nonresponse.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Complete\/near\u2010complete pathological response to neoadjuvant treatment is a surrogate marker of recurrence\u2010free, including distant metastasis\u2010free, survival in these patients.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35425","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T14:23:45Z","timestamp":1717683825000},"page":"3463-3472","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Long\u2010term efficacy of neoadjuvant\u2013adjuvant targeted therapy in borderline 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