Extramammary Paget Disease Treatment & Management

Updated: Jul 21, 2021
  • Author: Richard Harold "Hal" Flowers, IV, MD; Chief Editor: Dirk M Elston, MD  more...
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Treatment

Approach Considerations

Owing to the rarity of extramammary Paget disease (EMPD), a wide range of optimal treatment modalities has not yet been defined. The first-line treatment has long been surgical excision. Successful treatment has been achieved with both wide local excision and Mohs micrographic surgery (MMS). Conservative treatments may be considered in patients who are poor surgical candidates. Topical therapy with chemotherapeutic agents 5-fluorouracil (5-FU), bleomycin, and imiquimod has been infrequently reported in the literature. In addition, radiation therapy and photodynamic therapy have been suggested as potential treatment options, although further studies are needed to determine the efficacy of these modalities for EMPD patients. [26] Treatment of underlying malignancy is also warranted in cases of secondary EMPD.

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Surgical Excision

Margin-controlled surgical excision of all the involved epidermis is the current criterion standard treatment. Extramammary Paget disease (EMPD) frequently extends beyond the visibly involved margins. Obviously involved skin should be examined by using transverse frozen sections or serial vertical sections (see Workup). It has been suggested that multiple scouting biopsies performed before surgery may aid in planning a more precise initial excision. [11] However, a 2018 retrospective study found no utility for mapping biopsies with well-defined EMPD or when 2-cm margins could be achieved. [27]

Multifocal disease is a challenge for any surgical method that relies on contiguous tumor spread for effective margin control—even micrographic surgery. Currently, wide local excision and Mohs micrographic surgery (MMS) are the recommended excision options. The margin size for wide local excision has been debated in the literature. Some reports suggest using a margin extending 3-5 cm beyond the circumference of the tumor, [28, 29] while other data suggest a margin of 1 cm for lesions with clinically distinct margins. [30] When operating in the anogenital region, providers must consider the aesthetic and functional consequences patients may face after radical excision.

MMS offers lower recurrence rates after excision of primary tumors, with a smaller margin of normal skin removed. [28, 31] The reported recurrence rate of primary tumors after standard surgical excision ranges from 30-60%. The rate after excision with MMS ranges from 8-26%. A 2017 study found a recurrence rate of 11% after MMS of primary EMPD, compared with a 31% recurrence rate after standard excision. [32] MMS has also been shown to result in an over 10-fold reduction in the risk of positive margins as compared with wide local excision. [33] The use of intraoperative markers such as cytokeratin 7 (CK7) and carcinoembryonic antigen (CEA) during MMS has been suggested to improve visualization of Paget cells. [34, 35]

The average time to recurrence after excision is 2.5 years; however, cases have been reported with recurrence more than 10 years later. Although long-term outcomes are improved using MMS, some patients may not be able to afford the higher treatment costs.

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Chemotherapy

Several studies have reported the topical use of chemotherapeutic agents including 5-fluorouracil (5-FU), bleomycin, and imiquimod to treat extramammary Paget disease (EMPD). 5-FU and bleomycin have shown poor response rates with toxic adverse effects, including allergic reaction, severe pain, and desquamation. A few studies have shown clinical resolution of patients treated with topical 5-FU; however, biopsy specimens were often found to reveal histologic persistence of disease. [36, 37, 38]

Imiquimod 5% cream applied 3 times weekly for 16 weeks was found to induce complete resolution in a patient with perineal EMPD. [39] Imiquimod has also been found to be effective in combination with other modalities. One case report describes two patients with recurrent and extensive EMPD achieving complete remission after 5-aminolevulinic acid (5-ALA) photodynamic therapy and topical imiquimod. [40] Lesions were treated with 20% 5-ALA photodynamic therapy every 2 weeks for a total of 6 cycles followed by topical imiquimod every other day for 3 months. Topical imiquimod is considered a possible treatment option, especially when surgery is a challenge or contraindicated. However, more studies are needed to confirm the use of topical therapies for patients with EMPD. [39] Topical treatments may also be effective when combined with photodynamic therapy, although this combination therapy needs to be studied in a larger patient population before definitive recommendations can be made.

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Photodynamic Therapy

Photodynamic therapy may be a useful therapy for extramammary Paget disease (EMPD) confined to the epidermis as an adjunct to surgical treatment or as a primary therapy in patients who are poor surgical candidates. It is less invasive and can target large areas of skin in a single session. It has been used successfully to treat other superficial epidermal neoplasms such as actinic keratoses and superficial basal cell carcinomas, but has not yet been extensively studied as a treatment for EMPD. [26]

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Radiation

Radiation therapy is a potential primary and adjuvant treatment option for extramammary Paget disease (EMPD) and has been shown to have a response rate ranging from 62-100%. [26] It can also be effective in the local control of in situ lesions in inoperable cases of EMPD. [41, 42, 43] However, there have been no randomized controlled trials comparing surgical excision and radiotherapy. Radiation also compromises the skin's ability to heal, making further treatment after recurrence in patients previously treated with radiation challenging.

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Consultations and Long-Term Monitoring

Depending on the anatomic location of extramammary Paget disease (EMPD), treatment should be coordinated with an appropriate surgical subspecialist (eg, urologist, colorectal surgeon, gynecologist). Optimally, the consultant would have some experience treating this specific condition. Further consultation with a radiologist and a gastroenterologist may also be required to order appropriate screening examinations for internal malignancy.

Patients with EMPD require follow-up examination every 3 months after surgery to assess possible recurrence. This routine should continue for at least 24 months, after which time examinations may be done annually. Other endoscopic or imaging studies can be repeated on a regular basis according to the specific recommendations of the consultants.

A 2017 study found serum cytokeratin 19 fragment 21-1 (CYFRA 21-1) levels to be useful in monitoring tumor burden and treatment response. Compared with carcinoembryonic antigen (CEA) monitoring, CYFRA 21-1 levels were more sensitive in detecting tumor reduction as well as recurrence, with a corresponding decrease and increase in serum concentration, respectively. [44]

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