Penile cancer is a rare malignancy in most developed countries, but may represent a significant oncologic challenge in certain African, Asian, and South American regions. Various treatment approaches have been described in penile cancer, including radiotherapy. This review aimed to provide a synopsis of radiotherapy use in penile cancer management and the associated toxicities. In addition, we aimed to discuss palliative radiation for metastases to the penis and provide a brief overview of how tumor biology may assist with treatment decision-making.

Peer-reviewed manuscripts related to the treatment of penile cancer with radiotherapy were evaluated by a PubMed search (1960-2021) in order to assess its role in the definitive and adjuvant settings. Selected manuscripts were also evaluated for descriptions of radiation-related toxicity.

Though surgical resection of the primary is an excellent option for tumor control, select patients may be treated with organ-sparing radiotherapy by either external beam radiation or brachytherapy. Data from randomized controlled trials comparing radiotherapy and surgery are lacking, and thus management is frequently determined by institutional practice patterns and available expertise. Similarly, this lack of clinical trial data leads to divergence in opinion regarding lymph node management. This is further complicated in that many cited studies evaluating lymph node radiotherapy used non-modern radiotherapy delivery techniques. Groin toxicity from either surgery or radiotherapy remains a challenging problem and further risk assessment is needed to guide intensification with multi-modal therapy. Intrinsic differences in tumor biology, based on human papillomavirus infection, may help aid future prognostic and predictive models in patient risk stratification or treatment approach.

Penile cancer is a rare disease with limited clinical trial data driving the majority of treatment decisions. As a result, the goal of management is to effectively treat the disease while balancing the importance of quality of life through integrated multidisciplinary discussions. More international collaborations and interrogations of penile cancer biology are needed to better understand this disease and improve patient outcomes.