A Primer on Extramammary Paget's Disease for the Urologist

Joon Yau Leong; Paul H. Chung

Disclosures

Transl Androl Urol. 2020;9(1):93-105. 

In This Article

Non-surgical Treatment

Laser Therapy

Laser treatment for EMPD has garnered much interest as a conservative approach that may preserve anatomy and sexual function. Several reports have demonstrated the effectiveness of both the CO2 and Nd:YAG lasers to treat EMPD with the advantage of shorter operative and hospitalization times; however, the lack of histologic evidence for analysis, post-operative pain and anesthesia requirements have prompted both physicians and patients to seek alternative treatments.[48–50] Several reports have also noted high recurrence rates even up to 67–100% with this treatment modality.[51,52] This is likely due to the multifocal and extensive nature of EMPD lesions and the overly superficial ablative techniques provided by laser therapy which may not adequately treat microinvasive or invasive disease.[53]

Photodynamic Therapy (PDT)

PDT has been used to treat several neoplasms such as non-melanoma skin cancer, esophageal carcinoma and even non-small cell lung carcinoma.[54,55] It relies on the interaction between oxygen and a photosensitizer, either topical 5-aminolevulinic acid (ALA) or systemic porfimer sodium (PS), to generate reactive oxygen species that selectively destroy neoplastic tissue.[56] While topical ALA offers excellent cosmetic outcomes, its ability to treat invasive and multifocal extensions of the disease remains questionable.[57,58] While PS may alleviate this concern, systemic administration of a photosensitizer may generate a more severe local reaction which requires longer healing times. The safety and efficacy of PDT have yet to be clearly elucidated and therefore should be limited to patients who are unable to undergo surgery or with lesions in difficult anatomic locations.[59]

Radiotherapy

Use of radiation therapy in the treatment of EMPD has been reported in several case reports.[60–64] The majority of these patients presented with primary lesions on functionally delicate areas or were non-surgical candidates. Acute and chronic radiation toxicity is the major adverse effect. Initial investigations have described many different treatment techniques with a diverse range of radiation beam types, energy and dosages, all of which have yielded varying results and outcomes. Further studies evaluating the safety and efficacy of radiotherapy should be conducted before conclusions can be drawn.

Topical Chemotherapy

Topical chemotherapeutic agents have been utilized for EMPD. While these agents have reported response rates as high as 57–100% in localized disease, the side effects related to these agents including severe pain and dermatitis, moist desquamation and allergic reactions have mostly caused them to fall out of favor.[65–67] 5-fluorouracil (5-FU), mostly used as an adjunct to surgery, has been reported to be useful in clearing residual lesions which may not be excisable during surgery.[67] It may also have a role in highlighting subclinical areas of EMPD, allowing better visibility during surgery or be useful postoperatively to detect recurrence of disease.[68] Most investigators, however, recommend against the use of 5-FU as a monotherapy as it has only been shown to clear clinical but not pathological disease. Both studies by Haberman and Kawatsu described the use of 5-FU in genital EMPD and found that although the primary lesions cleared clinically, biopsy specimens still demonstrated persistent disease.[69,70] Topical bleomycin has also been considered for the treatment of EMPD. Watring et al. reported varying responses and outcomes in a series of seven patients treated for recurrent vulvar EMPD. Of these, four patients experienced complete therapeutic response with bleomycin, one of which required retreatment 30 months later and subsequently showed no evidence of recurrence.[65]

Topical 5% imiquimod cream, more commonly known for treating genital warts, has been increasingly prescribed for off-label use in localized EMPD. EMPD response rates have been reported to be as high at 52–80% with a 19% recurrence rate.[71] Imiquimod is an immune response modifier that enhances both innate and acquired immunity via the stimulation of cytokines, such as interferon-α and tumor necrosis factor-α. These cytokines in turn augment the anti-tumoral immune system to increase neoplastic cell death and destruction. Although the safety and efficacy of imiquimod for EMPD have yet to be completely exemplified, its side effect profile is better tolerated than much of the earlier chemotherapeutic agents, with mild dermatitis being the most commonly reported symptom.[2,72–74] Depigmentation is another adverse effect that has been previously described and may obscure visible margins on gross examination at the time of excision or post-operative follow-up.[75,76] Further studies thoroughly evaluating imiquimod are required before it may be considered as an adjunct to surgery, a potential alternative in non-surgical candidates or as part of a therapeutic combination with other non-invasive treatment modalities.[77]

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