Introduction:

Effective management of positive margins after organ-sparing surgery (OSS) of penile squamous cell carcinoma (PSSC) is crucial to improve outcomes and prevent disease recurrence and progression. Penile intraepithelial neoplasia (PeIN) poses a challenge because it can often present as positive margins on final pathology review after OSS despite intra-operative negative findings. This development can complicate postoperative management and there is limited literature addressing the ideal treatment course for patients with positive PeIN found in margins after OSS. This study looks to examine the management and natural course for this subset of patients with a small cohort at a single institution.

Methods:

We conducted a retrospective analysis of penile cancer patients treated with low-risk OSS (clinical stage Ta, Tis, T1-3) that were treated between May 2016 to December 2023. We defined low-risk OSS as wide local excision, circumcision, Mohs micrographic surgery, laser ablation, cryotherapy, partial glansectomy, and glans resurfacing. Patients who had total glansectomy, partial penectomy, or total penectomy at primary surgery, or who had nodal disease or metastasis at presentation, were excluded. All patients with PeIN positive primary resections were included.

Results:

A total of 18 patients with penile cancer treated with low-risk OSS and found to have positive PeIN surgical margins were identified. The cohort had a mean age of 65.9 years at time of primary surgery and a mean follow-up time of 35.9 months. Of those tested for high-risk HPV with P16 or in-situ hybridization, 13/16 tested positive (72.2%). Clinical T stage was primarily Tis (12/18, 66.7%) (Table1).

Surgical margins positive with PeIN were primarily managed with observation (n=11, 61.1%). 4/11 patients (36.4%) who were followed with observation had a recurrence. Of these, 3 recurrences were local, 2 were regional, and 1 was systemic (some patients had progressive recurrences). 6 patients (33.3%) were treated with re-resection and 3/6 (50%) had a recurrence. Of these, 3 were local recurrences, with 1 patient eventually developing regional and systemic disease. 1 patient died 22 months after re-resection. 1 patient (5.6%) was treated with immediate post-op topical 5FU and went on to develop a local and regional recurrence. The times to local, regional, and distant metastatic recurrence based on treatment type can be seen in Table 2.  

Conclusion:

Margins positive for PeIN introduces complexity to the postoperative management of OSS. Our data indicates that patients with PeIN positive margins in this small cohort faced high recurrence rates and disease progression regardless of the treatment approach. Time to regional recurrence was much higher after re-resection, but more data is required to determine the significance of this. Overall, our findings highlight the need for close follow-up of this subset of patients and the need for further research to establish evidence-based treatment protocols to improve outcomes.

Funding: N/A