Abstract:

Background: Evidence regarding long-term therapeutic outcomes and disease-specific survival (DSS) in Extramammary Paget's disease (EMPD) is limited.

Objectives: To assess DSS and outcomes of surgical and nonsurgical therapeutic modalities in a large cohort of EMPD patients.

Methods: Retrospective chart review of EMPD patients from 20 Spanish tertiary-care hospitals.

Results: Data on 249 patients with a median follow-up of 60 months were analyzed. The estimated 5, 10, and 15-year DSS was 95.9%, 92.9%, and 88.5%, respectively. A significantly lower DSS was observed in patients showing deep dermal invasion (≥1mm) or metastatic disease (p<0.05). A ≥50% reduction in EMPD lesion size was achieved in 100% and 75.3% of patients treated with surgery and topical therapies, respectively. Tumor-free resection margins were obtained in 42.4% of the patients after wide local excision (WLE). The 5-year recurrence-free survival (RFS) after Mohs micrographic surgery (MMS), WLE with tumor-free margins, WLE with positive margins, radiotherapy, and topical treatments was 63.0%, 51.4%, 20.4%, 30.1%, and 20.8%, respectively.

Limitations: Retrospective design.

Conclusions: EMPD is usually a chronic condition with a favorable prognosis. MMS represents the therapeutic alternative with the greatest efficacy for the disease. Recurrence rates in patients with positive margins after WLE are similar to those observed in patients treated with topical agents.

Introduction:

Extramammary Paget’s disease (EMPD) is an uncommon intraepithelial adenocarcinoma that develops in apocrine gland-rich areas. It usually presents as a persistent erythematous, asymmetrical, slowly enlarging plaque that may become scaly or ulcerative.

Treatment of EMPD can be challenging, since no standardized clinical practice guidelines are currently available. Wide local excision (WLE) has long been regarded as the gold standard for EMPD management. However, there is no agreement on the margin size. Mohs micrographic surgery (MMS) has emerged as a promising therapeutic alternative for EMPD, providing complete microscopic margin control.

Methods:

A retrospective, multicenter study took place at 20 Spanish tertiary-care hospitals. Patients diagnosed with EMPD from 1990 to 2022 were included. Subjects with a clinical follow-up of <6 months after diagnosis were excluded.

Data were collected via chart review. Response to treatment was evaluated at <3 months post-therapy and classified into categories: complete response (CR), partial response (PR), stable disease, and progression. Recurrence was defined as the appearance of a new lesion in previously treated areas.

Results:

249 patients were included. The median follow-up was 60 months. The median age at diagnosis was 71 years, and 71.5% of patients were female. The most commonly affected anatomical site was the female genitalia (57.4%). Dermal invasion was observed in 22.1% of cases, and metastatic disease was seen in 8.0%.

DSS:

At the end of the follow-up, 12 patients died due to EMPD. The estimated DSS at 5, 10, and 15 years was 95.9%, 92.9%, and 88.5%, respectively. DSS was significantly lower in patients exhibiting deep dermal invasion (≥1mm) or metastatic disease.

Treatment Outcomes:

Patients received various treatments, including surgical and nonsurgical methods. 66.3% underwent surgical treatment, while 26.5% received topical treatments as first-line therapy. Tumor-free margins were achieved in 42.4% after WLE. MMS showed the highest RFS (63.0% at 5 years), compared to WLE (33.7%) and topical agents (20.8%).

Discussion:

EMPD is a chronic disease with a favorable prognosis. MMS is the most effective treatment for controlling the disease. Interestingly, recurrence rates were similar between patients treated with topical agents and those undergoing surgery with positive margins.

Conclusions:

MMS should be considered the best therapeutic option for EMPD. However, nonsurgical therapies remain viable for noninvasive cases when MMS is not feasible. Future studies should focus on optimizing EMPD management strategies to balance disease control and patient quality of life.

Authors: Helena Escolà, MD; Beatriz Llombart, MD; Alba Escolà-Rodríguez, PharmD; Lucía Barchino-Ortiz, MD, PhD; Joaquim Marcoval, MD; Inmaculada Alcaraz, MD; Sònia Beà-Ardébol, MD, PhD; Agustí Toll, MD, PhD; Román Miñano-Medrano, MD; Pedro Rodríguez-Jiménez, MD, PhD; María López-Nuñez, MD; Carla Ferrándiz-Pulido, MD, PhD; Ane Jaka, MD, PhD; Emili Masferrer, MD, PhD; Rafael S. Aguayo-Ortiz, MD, PhD; Mireia Yébenes, MD; Jorge Arandes-Marcocci, MD; Verónica Ruiz-Salas, MD, PhD; Lucía Turrión-Merino, MD; Miquel Just, MD; Júlia Sánchez-Schmidt, MD; Lorena Leal, MD; Fátima Mayo-Martínez, MD; Lara Haya-Martínez, MD; Alejandra Sandoval-Clavijo, MD; Giulia Greta Dradi, MD; Yolanda Delgado, MD, PhD; Júlia Verdaguer-Faja, MD; Daniel López-Castillo, MD; Ramon M Pujol, MD, PhD; Gustavo Deza, MD, PhD.