Topical imiquimod in the treatment of extramammary Paget's disease: A 10 year retrospective analysis in an Asian tertiary centre

Liau, MeiQi May; Yang, Shiyao; Tan, Kong Bing; Aw, Chen Wee Derrick

doi:10.1111/dth.12394

Cited by 15 publications

(14 citation statements)

References 10 publications

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“…Extramammary Paget disease is associated with a high rate of local recurrence after surgery [7], which is attributed to the difficulty of determining margin status due to the EMPD’s multifocal pattern of growth, tendency to arise as an ill-defined non-mass lesion, and frequent extensive subclinical extension. Non-surgical treatment options for EMPD include topical imiquimod [33], photodynamic therapy, radiation therapy, carbon dioxide therapy, anti-androgen therapy, targeted anti-HER2/neu therapy (trastuzumab) [34,35], and cytotoxic chemotherapy [7,36]. Currently, there is no widely accepted treatment regimen for metastatic EMPD, and case studies and reports have shown that the systemic chemotherapy-based regimens used in the past had limited success.…”

Section: Discussionmentioning

confidence: 99%

Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted Therapy

Mauzo

Tetzlaff

Milton

et al. 2019

Cancers

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Extramammary Paget disease (EMPD) is a locally aggressive cutaneous malignancy that usually arises in anogenital or axillary skin. Immune checkpoint inhibitors targeting programmed cell death receptor (PD-1) and/or its ligand (PD-L1) are approved for the treatment of several types of cancer, and response to these generally correlates with increased PD-L1 expression by tumor cells. The expression of PD-L1 and composition and density of the tumor-associated immune infiltrate in EMPD have been little studied. To determine whether EMPD might be amenable to immune checkpoint blockade, we analyzed the expression of PD-1 and PD-L1 and the composition and density of the tumor-associated immune infiltrate in EMPD and evaluated associations between biomarker expression and clinicopathologic parameters. Twenty-one EMPD tumors were evaluated for tumor cell PD-L1 expression and for relative expression and distribution of CD3, CD8, PD-1, and PD-L1 in the tumor-associated immune infiltrate by using a combination of visual and image analysis (Aperio ImageScope). In addition, PD-L1 expression was assessed in 10 cases of mammary Paget disease (MPD). In EMPD cases, PD-L1 was expressed by tumor cells (3/21; 14%) and the tumor-associated immune infiltrate (15/21; 71%), and PD-1 was expressed by the tumor-associated immune infiltrate in all cases analyzed (18/18). However, PD-L1 expression by EMPD tumor cells did not correlate with the density of CD3-, CD8-, or PD-1-positive cells in the tumor-associated immune infiltrate or other clinicopathologic parameters. Furthermore, the density of CD3, CD8, PD-1, and PD-L1 in the tumor-associated immune infiltrate did not correlate with any clinicopathologic parameters evaluated with the exception that CD3 positive values were significantly higher in patients who were still alive (median, 1310 cells/mm2; range, 543–2115;) than in those who died (median, 611 cells/mm2; range, 481–908; p = 0.049). In all MPD cases, PD-L1 was absent in tumor cells but present in the tumor-associated immune infiltrate, and PD-L1 expression in lymphocytes was lower in patients with HER2/neu-positive than in those with HER2/neu-negative disease (p = 0.07). Our findings raise the possibility of therapeutic targeting of the PD-1/PD-L1 axis in EMPD.

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Section: Discussionmentioning

confidence: 99%

Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted Therapy

Mauzo

Tetzlaff

Milton

et al. 2019

Cancers

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“…Topical imiquimod has shown promise as a viable alternative to surgery. By stimulating the production of multiple cytokines, imiquimod activates the immune system to create an antitumor effect . Multiple studies have reported topical imiquimod 5% cream to be effective for EMPD, with response rates ranging from 52% to 100%, and recurrence rates up to 20% .…”

Section: Nonsurgical Interventionsmentioning

confidence: 99%

“…By stimulating the production of multiple cytokines, imiquimod activates the immune system to create an antitumor effect . Multiple studies have reported topical imiquimod 5% cream to be effective for EMPD, with response rates ranging from 52% to 100%, and recurrence rates up to 20% . In a recent prospective study by Sawada et al ., the response rate with imiquimod was 100%, with five of nine patients achieving complete response (complete clinical or histopathological remission).…”

Section: Nonsurgical Interventionsmentioning

confidence: 99%

Extramammary Paget's disease: a review of the literature

2018

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Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy. The disease typically affects older individuals aged 60-80 years and is seen most frequently in postmenopausal Caucasian women and Asian men. EMPD exhibits a predilection for the genital and perianal regions and may be associated with an underlying carcinoma in adjacent organs. EMPD presents a challenge in both diagnosis and management. Often treated empirically as various dermatitides, the correct diagnosis is frequently delayed by many years. Following diagnosis, an extensive search for an associated malignancy should be initiated. If invasive disease is present on biopsy, a sentinel lymph node biopsy may guide further treatment. Mohs micrographic surgery appears to be superior to wide local excision when considering tissue sparing ability and disease recurrence. Nonsurgical interventions have also been investigated with varied results. Regardless of treatment method, long-term follow-up is recommended to monitor for local disease recurrence, development of internal malignancy, regional lymphadenopathy, or distant metastasis.

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“…Imiquimod was evaluated by 13 studies (8 cohort studies, 5 case series) in 110 patients. CR was documented in 54% of patients, and 85% achieved clinical regression of 50% or more [43][44][45][46][47][48][49][50][51][52][53][54]60]. Given the propensity of EMPD for recurrence, posttreatment histological evaluation is of great importance.…”

Section: Discussionmentioning

confidence: 99%

“…Imiquimod is an immune response modifier that stimulates innate immune pathways (via induction of inflammatory cytokines, such as IFN-α, IL-6, and TNF-α) and adaptive immune pathways, resulting in an antitumor effect [59]. Eight cohort studies (3 prospective, 5 retrospective) and 5 case series (total 110 patients) investigated the effectiveness of imiquimod for EMPD at dose schedules ranging from daily to twice weekly for a duration of 2-56 weeks [43][44][45][46][47][48][49][50][51][52][53][54]60]. Overall, 54% (95% CI, 40-67%; I 2 = 37%) of patients achieved complete response (CR) and 85% (95% CI, 74-90%; I 2 = 0%) achieved clinical regression of 50% or more.…”

Section: Imiquimodmentioning

confidence: 99%

Nonsurgical Treatments for Extramammary Paget Disease: A Systematic Review and Meta-Analysis

et al. 2020

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Introduction: Surgery is commonly regarded as the mainstay of treatment of extramammary Paget disease (EMPD); however, nonsurgical approaches have gained popularity in recent years. Objectives: To review the published evidence for the efficacy and safety of nonsurgical modes of therapy for EMPD. Methods: A systematic review and meta-analysis of nonsurgical EMPD treatments was performed. The primary outcome was complete response (CR); secondary outcomes were clinical regression by ≥50%, adverse events, and recurrence rate. Results: The systematic review included 43 observational studies (341 patients; 7 prospective cohort studies, 19 retrospective cohort studies, and 17 cases series) evaluating 5 treatment modalities. Imiquimod (13 studies, 110 patients) administered at variable doses ranging from daily to twice weekly for 2-56 weeks demonstrated CR of 54% (95% CI, 40-67%; I 2 = 37%) and had a satisfactory safety profile. In 14 heterogeneous studies (122 patients) evaluating photodynamic therapy (PDT), only 36% (95% CI, 22-53%; I 2 = 52%) of patients achieved CR. Radiotherapy (12 studies, 67 patients) showed CR of 97%, but was associated with local and systemic side effects. Ablative lasers and topical fluorouracil and calcipotriene lacked adequate evidence of efficacy. Conclusions: Imiquimod and radiotherapy are the most appropriate nonsurgical modalities for EMPD treatment given their good efficacy and safety profile. PDT has limited efficacy but may be appropriate in selected clinical settings.

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Topical imiquimod in the treatment of extramammary Paget's disease: A 10 year retrospective analysis in an Asian tertiary centre

Cited by 15 publications

References 10 publications

Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted Therapy

Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted Therapy

Extramammary Paget's disease: a review of the literature

Nonsurgical Treatments for Extramammary Paget Disease: A Systematic Review and Meta-Analysis

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