Recent Advances in the Management of Penile Cancer: A Contemporary Review of the Literature

Penile cancer is a rare malignancy with an incidence rate of less than 1:100,000 in the US, but in some developing countries like Brazil, incidence rates are as high as 6.8:100,000. The significant geographic variation in incidence is likely attributed to differences in the prevalence of the human papilloma virus (HPV) infection, smoking, rates of neonatal circumcision, and sociodemographic risk factors.

In penile cancer, HPV is only associated with 35-50% of the cases, suggesting some penile cancers are not HPV-related. In countries like Canada, routine male HPV vaccination has been recommended since 2012. This has resulted in a decrease in the incidence of genital warts by 90%, but its protective effect against penile cancer is yet to be confirmed.

Penile cancer can present as a penile mass, an ulcerating lesion, or as a lesion that doesn’t heal following a short course of antibiotics or topical steroids. Some patients will also have palpable groin lymph nodes at presentation. Initial assessment should consist of a detailed history, a physical examination of the penis and lymph nodes, and a biopsy of the penile lesion.

Unfortunately, many patients will have their diagnosis delayed by more than 6 months. This is due in part to the significant social stigma associated with this disease, psychological impact, and challenges of describing the problem to their doctor or partner, and lack of awareness among patients. Factors positively associated with men´s help-seeking behavior include social support from spouses and knowledge about penile cancer gained through different sources. Delays in seeking medical attention can lead to significant post-treatment impairment in sexual function and satisfaction.

Despite appropriate treatment, the 5-year survival rate is only about 50% in an overall stage-independent analysis and only 27% in patients with node positive disease. Survival in the metastatic setting remains very poor, as systemic therapy options and prospective data guiding management are sparse. Fortunately, several clinical trials are now underway which offer hope for improved outcomes in this disease. In locally advanced disease, the InPACT phase III trial aims to determine the relative benefits and sequencing of surgery, chemotherapy, and chemoradiotherapy. In the metastatic setting, there are promising trials assessing the role of immunotherapy, either alone (ALPACA and PULSE trials), in combination with chemotherapy (HERCULES trial) or with tyrosine kinase inhibitors (NCT02496208).

This review highlights the importance of a multidisciplinary approach, preferably in high volume specialized centres, to develop an optimal management plan, help standardize care, and facilitate recruitment to clinical trials. We undertook this review, in collaboration with urologists and radiation oncologists who are experts in the field, to promote awareness of this rare disease among care providers, highlight optimal treatment strategies, and discuss ongoing research efforts and future directions.

Written by: Carlos E. Stecca, MD,¹ and Srikala S. Sridhar, MD, MSc, FRCPC²

Clinial Research Fellow at Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Medical Advisory and Research Board, an Associate Professor within the Department of Medicine, Division of Medical Oncology at the University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

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