- CONTEXT: Management of men with penile squamous cell carcinoma (PSCC) who have high-risk features following radical inguinal lymphadenectomy (ILND) remains controversial. European Association of Urology guidelines state that adjuvant inguinal radiotherapy (AIRT) is "not generally recommended". Despite this, many centres continue to offer AIRT to a subset of men. OBJECTIVE: To undertake a systematic review of the evidence on AIRT in node-positive men with PSCC. EVIDENCE ACQUISITION: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with no language or date restriction. Inclusion criteria were men with PSCC, pathologically staged inguinal node positive after ILND. The intervention included ILND with AIRT compared with ILND alone. Primary outcomes were relapse-free survival and toxicity. Risk of bias assessment was undertaken. EVIDENCE SYNTHESIS: A total of 913 abstracts were identified and screened independently by two reviewers. Seven studies were eligible for inclusion: six full-text manuscripts and one conference abstract. All were retrospective series and at a high risk of bias. The selected studies included 1605 men. Indications for AIRT varied but were typically involvement of two or more inguinal nodes or extranodal extension. Regional recurrence rate following AIRT was reported at 10-91.7%. Only one study reported on toxicity. Two studies compared recurrence and survival between men who received and who did not receive AIRT, with no significant difference (p>0.05). CONCLUSIONS: The evidence indicates that men treated with AIRT do not gain benefit with respect to relapse or survival. Uncertainty remains due to the retrospective nature and high risks of bias across the evidence. Given the lack of evidence supporting AIRT, it cannot be recommended for routine practice. PATIENT SUMMARY: Men with penile cancer who have involvement of the inguinal lymph nodes are at a high risk of cancer recurrence and death. We reviewed the literature to see if radiation treatment after removal of the nodes provided benefit. We did not find any good-quality evidence supporting this treatment, and hence it cannot be recommended.