Treatment Strategies for Extramammary Paget Disease: A Narrative Review of Current Status and Future Directions

Extramammary Paget disease (EMPD) is a rare epithelial malignancy that arises in the apocrine gland-bearing skin. Although localized intraepidermal EMPD generally follows an indolent clinical course, invasive EMPD is associated with lymph node metastasis, distant dissemination, and poor survival. Owing to its rarity, high-level evidence is limited and treatment strategies remain incompletely standardized, particularly for advanced disease. Recent advances in molecular profiling have revealed actionable therapeutic targets and created new opportunities for precision medicine.

A narrative review was conducted using the PubMed database through May 2026. Relevant literature regarding the epidemiology, prognostic factors, surgical and non-surgical management, lymph node management, radiotherapy, systemic therapies, molecularly targeted therapies, and future therapeutic directions for EMPD is reviewed and summarized.

Surgical excision remains the standard treatment for resectable localized EMPD. Margin-controlled approaches, including Mohs micrographic surgery, complete circumferential peripheral and deep margin assessments, and mapping biopsy-guided excision, have contributed to improved local disease control. Radiotherapy, topical imiquimod, and photodynamic therapy provide alternative treatment options for patients who are unsuitable candidates for surgery; however, recurrence remains a major challenge. The management of regional lymph node metastases includes sentinel lymph node biopsy, lymph node dissection, and adjuvant radiotherapy in selected patients. For metastatic disease, conventional chemotherapy based on taxanes and fluoropyrimidine/platinum combinations has demonstrated moderate antitumor activity but limited durability. Molecular characterization of EMPD has identified several promising therapeutic targets. HER2 overexpression or amplification, observed in approximately 30-40% of cases, has emerged as the most clinically validated biomarker, with trastuzumab-based therapies demonstrating substantial efficacy. Immune checkpoint inhibitors have shown activity in selected patients, particularly those with a high tumor mutational burden, although predictive biomarkers remain inadequately defined. Additional emerging targets include androgen receptor signaling, TROP2, NECTIN4, FOXM1, and PIK3CA-associated pathways.

In addition to conventional surgery- and chemotherapy-based approaches, biomarker-driven precision oncology is gaining attention as a treatment strategy for EMPD. HER2-targeted therapies, antibody-drug conjugates, and rationally selected immunotherapeutic strategies are expected to play increasingly important roles in the treatment of advanced disease. Continued translational research, international collaboration, and prospective clinical trials are essential to establish evidence-based treatment algorithms and improve outcomes in patients with this rare but potentially aggressive malignancy.