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enile cancer is an aggressive squamous cell carcinoma of the skin of the glans or of the inner layer of the prepuce, characterized by invasive growth and early metastatic spread to lymph nodes. While penile cancer is uncommon in Europe, incidence rates are very high in parts of South America and Africa. Since its treatment is often associated with significant cosmetic and functional defects, the disease is of critical importance to the affected men. Early metastatic spread to regional lymph nodes can be life-threatening. It is not uncommon that factors, both from the patient and the treating physician, are causing delays in diagnosis and start of treatment. With penile cancer being a comparatively rare disease, many physicians are unfamiliar with its management. Thus, several countries have centralized the treatment of this rare tumor. Penile cancer is an orphan disease. Due the low numbers of patients, no prospective randomized studies have become available. Most of the available data is from small retrospective studies; larger studies result from retrospective multicenter data collections. Thus, the level Summary Background: The incidence of penile cancer in Europe lies in the range of 0.9 to 2.1 cases per 100 000 persons per year. Carcinogenesis is associated with human papilloma virus (HPV) infection and with chronic inflammation. Methods: This review is based on publications (2010-2017) retrieved by a selective search in PubMed and EMBASE and on the guidelines of the European Association of Urology, the European Society of Medical Oncology, the National Comprehensive Cancer Network, and the National Institute for Health and Care Excellence (NICE). Results: 95% of cases of penile cancer are accounted for by squamous cell carcinoma, whose numerous subtypes have different clinical courses. Chronic preputial inflammation due to phimosis or lichen sclerosus is often associated with penile cancer. Circumcision lowers the risk of penile cancer (hazard ratio: 0.33). Maximally organ-preserving surgery with safety margins of no more than a few millimeters is the current therapeutic standard, because a local recurrence, if it arises, can still be treated locally with curative intent. Local radiotherapy can be performed in early stages. Lymphogenic metastasis must be treated with radical lymphadenectomy and adjuvant chemotherapy. Patients with clinically unremarkable inguinal lymph nodes nonetheless need invasive lymph node staging because of the high rate of lymphogenic micrometastasis. Conclusion: Penile cancer is curable in all early stages with the appropriate treatment, but its prognosis depends crucially on the proper management of the regional (i.e., inguinal) lymph nodes. In many countries, the treatment of this rare disease entity has been centralized.

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