Introduction:

Extramammary Paget’s disease (EMPD)in men is a rare intra-epithelial malignancy believed to arise from apocrine gland-containing skin including the penis, scrotum, and axillary regions. This malignancy is usually isolated to the epidermis but can invade the dermis and spread to regional lymph nodes or distant sites. In this study, we aim to examine patient characteristics and clinical factors to define factors that may influence post-treatment disease recurrence.

Methods:

An institutional review board-approved retrospective review was performed.  Patients with the diagnosis of extramammary Paget’s disease of the scrotum and/or penis between 3/24/1994 and 9/14/2023 were included. Seventy-seven patients met the study criteria and were included. A univariate analysis was then performed to examine associations between clinicopathologic factors and predictors of disease recurrence. A p-value of <0.05 was considered to be statistically significant. The Kaplan-Meier method was used to assess overall survival, recurrence free survival, and cancer-specific survival.

Results:

Of the seventy-seven patients identified, Sixty-six (85.7%) were Caucasian and presented with disease isolated to the genital region (79.5%, n=58).  Most patients reported a rash as the only presenting symptom (72.7%, n=56) and twenty-six demonstrated  multifocality (33.8%). Median time from diagnosis to referral was 24 months (IQR 12-48). Prior to referral,  topical therapy only (63.6%, n=49), or non-excisional strategies were most common (topical agent with laser ablation (3.9%, n=3), laser ablation only [1.3%, n=1],or  cryoablation± cauterization  (n=2, 2.6%). Wide local excision,  Mohs procedure, or combination was performed in n=15(19.5%), n=3 (3.9%), or n=1 (1.3%) patients, respectively.

Subsequent to referral , patients were treated with either  wide local excision (WLE) guided by immediate frozen section margin assessment (76.6%, n=59), Mohs procedure (14.3%%, n=11), WLE with urethrectomy (3.9%, n=3), or laser ablation (1.3%, n=1). Three patients did not undergo any treatment after presentation to MD Anderson.

Lymph node biopsy was performed in 13 patients with 10 being positive (76.9%).  Pathologic analysis  revealed intraepidermal spread in 22 patients (28.6%) and with dermal invasion in 55 patients (71.4%).  Lymphovascular invasion, perineural invasion, or positive surgical margins  was noted in n=9 (11.7%), n=3 (4.3%), and  n=11 (14.3%) patients, respectively.  The median follow-up among all patients was 24 mos (IQR 10.5-64.5). Fifteen patients (19.5%)  exhibited disease recurrence post therapy at  a median of 19.5 mos. Estimated  5-year relapse-free survival was 74%.  Recurrences were  local in 12 patients (67%), regional in 4 patients (33%), and distant in 1 patient (6.7%). Univariate associations with recurrence included  Asian race, and history of genital trauma, prior history of WLE or Mohs surgery, clinical node positive or distant metastatic disease on presentation, positive surgical margins, positive lymph nodes , lymph node dissection, extranodal extension of cancer, and prior recurrence.  At 2 years, overall survival was 77.9%, while cancer specific survival was 92.2%. Of the 6 patients who died of disease,  all had regional metastasis (100%) and 5 developed distant metastasis (83.3%). Furthermore, 8 (44%) of the patients who died from all causes had dermal invasion on pathology, including 5 of the patients who died of disease.

Conclusion:

Extramammary Paget’s disease is a rare intra-epithelial malignancy that can progress in a radial fashion or become invasive with the potential for  regional or distant metastases.  WLE with immediate frozen section margin assessment or  Moh’s excision procedures provided local disease control in the majority of patients with excellent short term cancer specific survival. Based on recurrence data, WLE or Mohs among pts w/ prior topical and non-excisional therapies can salvage these patients. For patients with regional or distant metastasis, novel therapies are needed to improve clinical outcomes.

Funding: The Department of Urology Penile Cancer Research Fund