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Patients with node\u2010positive penile SCC who underwent inguinal or ilioinguinal lymphadenectomy were divided into three cohorts: a discovery set, a development set and a validation set. The local ethics committee approved the study. The primary endpoint was cancer\u2010specific survival (CSS). At the discovery stage, 17 CpG sites were significantly associated with CSS. In the development set, we constructed a 3\u2010CpG\u2010based prognostic score for survival prediction. The hazard ratio (HR) of the panel (dichotomized using the optimal cutoff) was 5.8 in the multivariate analyses (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001). The addition of the methylation score significantly improved the pN\u2010stage C\u2010index from 0.70 to 0.79 (incremental <jats:italic>C<\/jats:italic> = 0.09, <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001). In the validation set, the methylation panel showed a HR of 9.9 in the multivariate analyses. The addition of the molecular marker improved the pN\u2010stage C\u2010index from 0.69 to 0.78 (incremental <jats:italic>C<\/jats:italic> = 0.09, <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001). The methylation score remarkably separated survival curves in different pN stages, which indicate that the tool can be applied to tailor the treatment in both preinguinal and postinguinal lymphadenectomy settings. We developed and validated a prognostic methylation panel for node\u2010positive penile SCC. The tool may aid in the risk stratification of the population with heterogeneous outcomes and needs prospective validation. Patients in high\u2010risk group may benefit from more aggressive therapy or clinical trials.<\/jats:p>","DOI":"10.1002\/ijc.33355","type":"journal-article","created":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T21:41:40Z","timestamp":1603402900000},"page":"1289-1298","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of a methylation panel aid in risk stratification in node\u2010positive penile squamous cell carcinoma"],"prefix":"10.1002","volume":"148","author":[{"given":"Weijie","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology Shanghai Medical College, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangning","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer 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