Topical Therapy for non-invasive penile cancer (Tis)—updated results and toxicity

Abstract

Penile cancer is a rare malignancy estimated to affect 26,000 men globally each year. The association with penile cancer, in particular non-invasive disease, and human papilloma virus (HPV) is well known. Ninety-five percent of cases of penile cancer are squamous cell carcinoma (SCC), which are staged using the TNM staging system. Terminology describing the histological appearance of non-invasive penile cancer has changed with all cases grouped under the umbrella term of penile intraepithelial neoplasia (PeIN); either undifferentiated or differentiated. This replaces previous terms such as carcinoma in situ (CIS) and eponymous names such as Bowen’s disease. This change is recognised by the World Health Organisation (WHO). The topical treatments most commonly used for PeIN are 5-fluorouracil (5-FU) and imiquimod (IQ). Other treatments such as photodynamic therapy (PDT) are used but to a lesser degree. The evidence for all of these treatments is heterogenous with no randomised data available. Overall up to 57% complete response has been reported with a low number of serious adverse events. In this article, we aim to review the available evidence for the topical treatment of non-invasive penile cancer specifically regarding its efficacy and toxicity.

The Diagnosis and Treatment of Penile Cancer

“…This can be achieved using focal chemotherapy or immunotherapy, laser ablation, radiation therapy or surgery. Carcinoma in situ (pTis) can be treated successfully in half of the cases using topical immunotherapy or chemotherapy (imiquimod, 5fluorouracil, applied as an aqueous solution) (14). Alternative treatment options-also for recurrence or persistence of the lesion-to be considered include laser (CO2, Neodym:YAG) ablation, complete removal of the epithelium of the glans ("glans resurfacing") or radiation therapy.…”

“…Local radiation therapy is a recommended option for tumors up to a maximum size of 4 cm in the stages T1 and T2 (4). Local brachytherapy achieves lower local control rates compared to surgical treatment (70-90% versus 90-92% and 94-96% for glansectomy and glans resurfacing, respectively) (14,15,(22)(23)(24)(25). With the majority of cases of penile cancer being treated surgically, data on radiation therapy are scarce.…”

Penile sparing therapy for penile cancer

“…5-FU exerts its anti-tumour effects via impairing the normal synthesis and functioning of RNA and DNA (62). Tumour cells are affected more than normal cells due to the increased uptake of 5-FU in rapidly dividing cells (63). The mechanism of action of imiquimod is primarily based on activating the innate immune system (64).…”

“…Significant inflammation can result following 5-FU treatment and is reported in 36.8% in one study, which included one patient who was admitted for pain control and one patient who developed neo-phimosis (65). Toxicity following imiquimod is extrapolated from extragenital disease (63). The most common toxicity is local inflammatory reaction, and other side effects include flulike symptoms, myalgia and headache (63).…”

“…Toxicity following imiquimod is extrapolated from extragenital disease (63). The most common toxicity is local inflammatory reaction, and other side effects include flulike symptoms, myalgia and headache (63).…”