Extramammary Paget's disease: Updates in the workup and management

doi:10.1016/j.ajur.2022.08.001

Asian Journal of Urology, 2022, 9 (4): 451-459 doi: 10.1016/j.ajur.2022.08.001

Special Issue on Advancing the Field of Rare Genitourinary Tumors: Challenges and Opportunities: Reviews

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Extramammary Paget's disease: Updates in the workup and management

Reza Nabavizadeh^a,*(

),Khushali B. Vashi^a,Behnam Nabavizadeh^b,Vikram M. Narayan^a,Viraj A.Master^a,c

^aDepartment of Urology, Emory University School of Medicine, Atlanta, GA, USA
^bDepartment of Urology, Weill Cornell Medicine, New York, NY, USA
^cWinship Cancer Institute, Atlanta, GA, USA

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Abstract

Objective: Extramammary Paget's disease (EMPD) is a rare cutaneous malignant disease. Due to its rarity, there is a paucity of data regarding best treatment strategy. EMPD primarily affects apocrine gland-bearing skin areas such as the vulva, scrotum, and penis. Our objective was to provide a present-day rationale for diagnosis, pathogenesis, and treatment of EMPD with a focus on recent progress in workup and management of the disease.

Methods: Literature on EMPD until February 2022 was assessed through PubMed, MEDLINE databases, and Google scholar. A narrative review of the most relevant articles was provided.

Results: EMPD usually presents with indolent growth while usually being diagnosed primarily as carcinoma in situ. The foundation of EMPD treatment centers around prompt and accurate diagnosis, wide local or Mohs micrographic surgical excision with proper management towards the margin status, and careful consideration for lymphadenectomy in patients with regionally positive disease. Conventional chemotherapies are alternative treatments modality for patients with distant metastases; however, they sometimes have suboptimal efficacy. At present, there is no agreement regarding adjuvant or systemic therapies, although recent studies have shown several insights into the molecular pathogenesis, tumor biology, and genomics of the development and advancement of EMPD, which may lead to novel and targeted treatment approaches for metastatic EMPD in the future.

Conclusion: Patients with EMPD should seek care from physicians with expertise in disease management and patient counseling. These patients should be surveilled with close follow-up to evaluate them for disease recurrence or progression. Global collaborations with groups such as the Global Society for Rare Genitourinary Tumors, and especially patient support groups are crucial in designing clinical trials to help elucidate more robust data in this orphan disease.

Key words： Extramammary Paget's disease Extramammary Paget's malignancy Genitourinary Paget's disease Rare genitourinary tumors

Received: 19 March 2022 Available online: 20 October 2022

Corresponding Authors: Reza Nabavizadeh E-mail: rnabavi@emory.edu

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Cite this article:

Reza Nabavizadeh,Khushali B. Vashi,Behnam Nabavizadeh, et al. Extramammary Paget's disease: Updates in the workup and management[J]. Asian Journal of Urology, 2022, 9(4): 451-459.

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http://www.ajurology.com/EN/10.1016/j.ajur.2022.08.001 OR http://www.ajurology.com/EN/Y2022/V9/I4/451

Initial presentation of an ill-defined eczematous lesion in the apocrine gland-bearing penoscrotal area. The patient signed informed written consent to procedures and publication.

A summary of different management strategies for EMPD.

Surgical management of extramammary Paget's disease. (A) Grossly involved skin is resected first; (B) The margin is marked and resected separately for pathologic assessment. The patient signed informed written consent to procedures and publication.

Post-operative wound healing following resection and skin graft for extramammary Paget's disease. (A) Immediate; (B) 1-month; (C) 2-month; (D) 1-year. The patient signed informed written consent to procedures and publication.

Management	Modality	Study	Case, n	Outcome	Best clinical use
Non-surgical management	Imiquimod	Snast et al., 2020 [18]	110	? CR in 54% (95% CI 40%-67%) ? Clinical regression of greater than 50% in 85% of patients (95% CI 74%-90%) ? 40% of patients had recurrence
	5-FU	Molina et al., 2019 [19]	3 (recurrent refractory EMPD cases) product used: 5% 5-FU cream with 0.005% calcipotriene	? No patient was found to have a CR; however, they had minimal degree of clinical improvement
	PDT	Ishizuki and Nakamura, 2021 [5]	NA	? Multiple cases have shown antitumor response with PDT ? PDT can only be used as palliative treatment to reduce symptoms	? EMPD lesions of <4 cm
	Radiation doses ranged from 10 Gy to 64 Gy delivered in 1-57 fractions	Snast et al., 2020 [18]	67	? 97% of patients attained CR ? Patients achieved at least a 50% improvement ? 34% of patients (95% CI 23%-47%) who reached CR had disease recurrence	? Primary or adjuvant setting
	Holmium laser	Li et al., 2014 [22]	61	? Shorter operative time, less bleeding, but with longer wound healing period.	? Disease limited to the dermis and epidermis areas
	Carbon dioxide laser	Choi et al., 2001 [23] and Louis-Sylvestre et al., 2004 [24]	3	? Higher recurrence rates of 67%-100%; ? Conclusion: use of laser ablation after wide local surgical excision	? Primary or adjuvant setting
Surgical management	Wide excision (1 cm incision margins)	Murata et al., 2005 [26]	46	? Clinically determined border of well-defined lesions of EMPD corresponded well to the histopathologic border ? No local recurrence was observed in 24-115 months of follow-up	? Well-defined EMPD lesions only
	Mohs micrographic surgery	Long et al., 2017 [30]	154	? 10-fold reduction in the risk of positive margins ? Recurrence risk was 3.5 (95% CI 1.7-7.2, p<0.001) times more in those with positive pathologic margins compared to those with negative margins	? 1st line: primary excision or for recurrences from wide local excision
	Punch biopsy	Adashek et al., 2019 [27]	41	? Cases with carcinoma in situ showed nodular growth patterns and glandular formations
	Sentinel lymph node biopsy	Fujisawa et al., 2015 [31]	151	? Multivariate analysis revealed that dermal invasion (odds ratio 5.8, p=0.04) and lympho-vascular invasion (odds ratio 18.0, p=0.0023) were independent factors ? No difference in survival between patients with or without sentinel lymph node metastasis (p=0.71)	? In cases where regional metastasis is present
Systemic therapy	FECOM therapy	Oashi et al., 2014 [33]	7	? Partial response found in four patients ? Median overall survival was 9.4 (range: 7.6-17.3) months ? Median progression-free survival was 6.5 (range: 2.6-7.9) months ? 1-year survival rate was 43%	? Metastatic EMPD
	HER2	Tanaka et al., 2013 [34]	104	? HER2 protein was overexpressed in 16 cases (15%) in total	? Deep invasion and lymph-node metastasis ? Aggressive EMPD cases
	Combination chemotherapy of low-dose FP	Tokuda et al., 2015 [36]	22	? The overall survival ranges were 5-51 (median: 12) months in all 22 patients, 6-51 (median: 13) months in the 13 patients showing CR or PR, and 5-12 (median: 11) months in the 6 SD patients.	? Advanced EMPD cases
	Trastuzumab	Fukuda and Funakoshi, 2018 [37]	3	? Two cases achieved PR ? One case showed CR	? Metastatic EMPD
	Trastuzumab+paclitaxel	Fukuda and Funakoshi, 2018 [37]	3	? Three cases showed PR	? Metastatic EMPD
	Docetaxel+S-1	Fukuda and Funakoshi, 2018 [37]	4	? Three cases achieved PR; one case achieved CR.	? Metastatic EMPD

A summary of studies included in this review article.

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