{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T03:09:52Z","timestamp":1783652992054,"version":"3.55.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"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>Background<\/jats:title><jats:p>Regional lymphadenectomy was once considered as the standard treatment for melanoma patients with positive SLNB result, aimed at reducing the risk of recurrence and metastasis. However, recent researches have suggested multiple key roles of regional lymph node clusters in anti-tumor immune responses. Therefore, in the era of immunotherapy, whether lymph node dissection ultimately benefits patients remains to be determined, especially in acral melanoma, the leading subtype in east Asian population, which has a poorer response to immune checkpoint inhibitors (ICIs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively analyzed 172 patients with resectable advanced melanoma (stage III-IV, M1a) from a tertiary center and categorized them into four groups based on treatment regimens: immunotherapy group, observation group, neoadjuvant group, adjuvant group. In patients receiving immunotherapy (including immunotherapy group, neoadjuvant group, and adjuvant group), anti-PD-1 antibody was given accompanied with interferon-\u03b11b.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>With a median follow-up of 18.87 months, multivariable analysis confirmed significantly longer RFS for neoadjuvant versus adjuvant group. The adjusted HR was 2.02 (95% Cl 1.05\u20133.89, p= 0.035). Numerical improvements over immunotherapy and observation groups did not reach statistical significance, with p-values of 0.120 and 0.073 respectively. The 2-year RFS rate was significantly higher at 39.5% versus 13.8%. Notably, surgery-related adverse events occurred in 50.0% of patients (12.5% grade \u22653), with no significant differences observed among groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrates that in Chinese patients with advanced melanoma, neoadjuvant therapy is associated with significantly prolonged RFS compared to adjuvant therapy, with suggestive but non-significant advantages against other approaches.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1673308","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T05:51:36Z","timestamp":1759297896000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Neoadjuvant outperforms adjuvant regimens in resectable advanced Chinese melanoma patients: lymph node preservation as a key immunological advantage"],"prefix":"10.3389","volume":"16","author":[{"given":"Shuguang","family":"Hou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bolun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanfu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guannan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1056\/NEJMoa1310460","article-title":"Final trial report of sentinel-node biopsy versus nodal observation in melanoma","volume":"370","author":"Morton","year":"2014","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa060992","article-title":"Sentinel-node biopsy or nodal observation in melanoma","volume":"355","author":"Morton","year":"2006","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2016.0051","article-title":"Melanoma, version 2.2016, nccn clinical practice guidelines in oncology","volume":"14","author":"Coit","year":"2016","journal-title":"J Natl Compr Canc Netw"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1613210","article-title":"Completion dissection or observation for sentinel-node metastasis in melanoma","volume":"376","author":"Faries","year":"2017","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.02306","article-title":"Final analysis of decog-slt trial: no survival benefit for complete lymph node dissection in patients with melanoma with positive sentinel node","volume":"37","author":"Leiter","year":"2019","journal-title":"J Clin Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-010-1203-0","article-title":"The impact on morbidity and length of stay of early versus delayed complete lymphadenectomy in melanoma: results of the multicenter selective lymphadenectomy trial (i)","volume":"17","author":"Faries","year":"2010","journal-title":"Ann Surg Oncol"},{"key":"B7","unstructured":"Nccn guidelines for patients\u00ae: melanoma\n          \n          2025"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124507","article-title":"Tumor-draining lymph nodes are pivotal in pd-1\/pd-l1 checkpoint therapy","volume":"3","author":"Fransen","year":"2018","journal-title":"JCI Insight"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000000774","article-title":"Impact of lymphadenectomy extent on immunotherapy efficacy in post-resectional recurred non-small cell lung cancer: a multi-institutional retrospective cohort study","volume":"110","author":"Deng","year":"2024","journal-title":"Int J Surg"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1562797","article-title":"Immune microenvironment of tumor-draining lymph nodes: insights for immunotherapy","volume":"16","author":"Wei","year":"2025","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01851-x","article-title":"Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab and nivolumab in high-risk stage iii melanoma: the prado trial","volume":"28","author":"Reijers","year":"2022","journal-title":"Nat Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2022.100469","article-title":"Acral lentiginous melanoma histotype predicts outcome in clinical stage i-ii melanoma patients: an international multicenter study","volume":"7","author":"Mandal\u00e0","year":"2022","journal-title":"Esmo Open"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2020.02.010","article-title":"Acral lentiginous melanoma: incidence and survival in the United States, 2006-2015, an analysis of the seer registry","volume":"251","author":"Huang","year":"2020","journal-title":"J Surg Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.canlet.2020.05.035","article-title":"Stat3: a key signaling molecule for converting cold to hot tumors","volume":"489","author":"Hu","year":"2020","journal-title":"Cancer Lett"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.3781","article-title":"The efficacy of anti-programmed cell death protein 1 therapy among patients with metastatic acral and metastatic mucosal melanoma","volume":"10","author":"Ogata","year":"2021","journal-title":"Cancer Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1200\/GO-24-00644","article-title":"Adjuvant anti\u2013pd-1 monotherapy versus observation for stage iii acral melanoma of the sole: a multicenter retrospective study in Japanese patients","volume":"11","author":"Koizumi","year":"2025","journal-title":"Jco Glob Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1802357","article-title":"Adjuvant pembrolizumab versus placebo in resected stage iii melanoma","volume":"378","author":"Eggermont","year":"2018","journal-title":"N Engl J Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000001306","article-title":"Surgical margins in head and neck squamous cell carcinoma: a narrative review","volume":"110","author":"Chen","year":"2024","journal-title":"Int J Surg"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.soi.2025.100131","article-title":"Real world experience with omission of therapeutic lymph node dissection in clinical stage iii Malignant melanoma treated with checkpoint or kinase inhibition systemic therapy","volume":"2","author":"Kirsch","year":"2025","journal-title":"Surg Oncol Insight"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-021-02029-0","article-title":"Impact of the changes in the completion lymph node dissection criteria and approval of adjuvant therapies on the real-world outcomes of Japanese stage iii melanoma patients","volume":"26","author":"Ogata","year":"2021","journal-title":"Int J Clin Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2024.115141","article-title":"Impact of personalized response-directed surgery and adjuvant therapy on survival after neoadjuvant immunotherapy in stage iii melanoma: comparison of 3-year data from prado and opacin-neo","volume":"214","author":"Reijers","year":"2025","journal-title":"Eur J Cancer"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211437","article-title":"Neoadjuvant-adjuvant or adjuvant-only pembrolizumab in advanced melanoma","volume":"388","author":"Patel","year":"2023","journal-title":"N Engl J Med"},{"key":"B23","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1186\/s12957-015-0701-8","article-title":"The long-term results and prognostic significance of cutaneous melanoma surgery using sentinel node biopsy with triple technique","volume":"13","author":"Rutkowski","year":"2015","journal-title":"World J Surg Oncol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1136\/bmj.38849.680509.AE","article-title":"Value of sentinel node status as a prognostic factor in melanoma: prospective observational study","volume":"332","author":"Kettlewell","year":"2006","journal-title":"Bmj"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.50.7681","article-title":"Nonsentinel lymph node status in patients with cutaneous melanoma: results from a multi-institution prognostic study","volume":"32","author":"Pasquali","year":"2014","journal-title":"J Clin Oncol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.ccell.2020.09.001","article-title":"The pd-1\/pd-l1-checkpoint restrains t cell immunity in tumor-draining lymph nodes","volume":"38","author":"Dammeijer","year":"2020","journal-title":"Cancer Cell"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0198-0","article-title":"Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage iii melanoma","volume":"24","author":"Blank","year":"2018","journal-title":"Nat Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15174384","article-title":"Modern approach to melanoma adjuvant treatment with anti-pd1 immune check point inhibitors or braf\/mek targeted therapy: multicenter real-world report","volume":"15","author":"Placzke","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13175238","article-title":"Treatment patterns and outcomes of stage iii melanoma patients with positive sentinel lymph node biopsy: a real-life experience","volume":"13","author":"Roccuzzo","year":"2024","journal-title":"J Clin Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1673308\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T05:51:38Z","timestamp":1759297898000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1673308\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,1]]},"references-count":29,"alternative-id":["10.3389\/fimmu.2025.1673308"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1673308","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,1]]},"article-number":"1673308"}}