Topical chemotherapy for penile carcinoma in situ: Contemporary outcomes and reported toxicity

Purpose: The toxicity of topical chemotherapeutics has been well-characterized in extra-genital squamous cell carcinoma; however, there is limited data regarding the use of topical agents for penile squamous cell carcinoma in situ (CIS). We aim to describe the clinical outcomes and toxicities associated with the use of topical fluorouracil and imiquimod for penile CIS.

Materials and methods: We performed an observational analysis of penile CIS cases treated with topical chemotherapy from 2009 to 2019 at a tertiary cancer center.

Results: Twenty patients with penile CIS received fluorouracil (n= 17, 85%) or imiquimod (n = 3, 15%). The median age was 66 years. The median follow-up was 18 months. Complete response (CR) was achieved in 65% (n= 13/20), partial response in 25% (n = 5/20), and no response in 10% (n = 2/20). Overall, 50% required additional alternative treatments due to lack of CR or relapse. The median recurrence-free survival was 14 months. Fifty percent of patients reported Common Terminology Criteria for Adverse Events v5.0 grade 1 to 2 acute toxicities, including local skin irritation (40%), pain (35%), dysuria (5%), or nausea (5%). Only 65% completed the full course of treatment. Nonadherence was associated with a diminished CR rate of 28.6%.

Conclusions: Topical chemotherapy is a reasonable first-line therapy for penile CIS. A substantial proportion of patients experience acute toxicity and are unable to complete the full course of therapy. We recommend that patients with penile CIS be monitored regularly in order to promptly address issues with adherence and toxicity associated with topical treatment.

Keywords: 5-Fluorourocil; Acute toxicity; Imiquimod; Noninvasive penile cancer; Penile preserving strategies; Topical chemotherapy.