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Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease

Educational Objective
To identify the key insights or developments described in this article
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Importance  Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms.

Objective  To develop recommendations for the care of adults with EMPD.

Evidence Review  A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD.

Findings  The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years.

Conclusions and Relevance  Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.

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Article Information

Accepted for Publication: August 31, 2021.

Published Online: January 20, 2022. doi:10.1001/jamaoncol.2021.7148

Corresponding Author: Murad Alam, MD, MSCI, MBA, Feinberg School of Medicine, Northwestern University, 676 N St Clair St, Ste 1600, Chicago, IL 60611 (m-alam@northwestern.edu).

Author Contributions: Drs Kibbi and Alam had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Kibbi, Owen, and Worley contributed equally to this manuscript and are co–first authors. Dr Alam was the Guidelines Chair. Drs Kibbi, Owen, and Worley contributed equally to the drafting and revision of the manuscript.

Concept and design: Kibbi, Owen, Worley, Aung, Barker, Cartee, Choi, Chung, Dorigo, Fujisawa, Halfdanarson, Kanitakis, Khan, Lawrence, Maher, Ross, Solomon, Tolia, Arai, Brackett, Poon, Alam.

Acquisition, analysis, or interpretation of data: Kibbi, Owen, Worley, Wang, Harikumar, Downing, Aasi, Bolotin, Bordeaux, Chandra, Cho, Cliby, Dorigo, Eisen, Fujisawa, Golda, Halfdanarson, Iavazzo, Jiang, Kim, Kuzel, Leitao, MacLean, Maher, Mittal, Nehal, Ozog, Pettaway, Ross, Rossi, Servaes, Thomas, Voelzke, Waldman, Wong, Zhou, Brackett, Ibrahim, Kang, Poon, Alam.

Drafting of the manuscript: Kibbi, Owen, Worley, Wang, Fujisawa, Halfdanarson, MacLean, Ross, Solomon, Wong, Arai, Brackett, Kang, Alam.

Critical revision of the manuscript for important intellectual content: Kibbi, Owen, Worley, Harikumar, Downing, Aasi, Aung, Barker, Bolotin, Bordeaux, Cartee, Chandra, Cho, Choi, Chung, Cliby, Dorigo, Eisen, Golda, Halfdanarson, Iavazzo, Jiang, Kanitakis, Khan, Kim, Kuzel, Lawrence, Leitao, MacLean, Maher, Mittal, Nehal, Ozog, Pettaway, Ross, Rossi, Servaes, Solomon, Thomas, Tolia, Voelzke, Waldman, Wong, Zhou, Arai, Ibrahim, Kang, Poon, Alam.

Statistical analysis: Kibbi, Owen, Worley, Harikumar, Wong.

Obtained funding: Alam.

Administrative, technical, or material support: Kibbi, Worley, Fujisawa, Iavazzo, Ozog, Pettaway, Rossi, Solomon, Wong, Brackett, Ibrahim, Kang, Poon.

Supervision: Barker, Bolotin, Bordeaux, Cartee, Cliby, Eisen, Jiang, Kim, Kuzel, Lawrence, Nehal, Pettaway, Thomas, Voelzke, Arai, Alam.

Conflict of Interest Disclosures: Dr Worley reported serving as an advisory board member for Castle Biosciences outside of the submitted work. Dr Barker reported receiving grants from the National Institutes of Health through subcontracts from Physical Sciences Incorporated, EMD Serono, Alpha Tau Medical, Merck, and Amgen; personal fees from the American Society for Radiation Oncology, the American Brachytherapy Society, and Regeneron; and nonfinancial support from Alpha Tau Medical, H. Lee Moffitt Cancer Center, and Regeneron outside the submitted work. Dr Bolotin reported serving as an investigator without compensation on clinical trials for Replimune and Pelle Pharm outside the submitted work. Dr Chandra reported serving as an advisory board member for Exicure, Novartis, Bristol Myers Squibb, Sanofi Genzyme, and Regeneron outside the submitted work. Dr Choi reported receiving personal fees from Regeneron, Parexel, OnQuality Pharmaceuticals, Bristol Myers Squibb, and Kyowa Kirin International outside the submitted work. Dr Halfdanarson reported receiving personal fees from Curium, Lexicon, Terumo, and ScioScientific; receiving research support paid to the institution from Thermo Fisher Scientific, Basilea, Turnstone Biologics, Agios, and Novartis; and serving as a consultant with fees paid to the institution for ITM, Ipsen, and Novartis outside the submitted work. Dr Leitao reported receiving funding in part through the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748; serving on the advisory board for and receiving personal fees from Ethicon/J&J and Takeda; and receiving grants to the institution from KCI/Acelity outside the submitted work. Dr Ross reported being an employee of Foundation Medicine Inc, being an equity owner in Roche Holdings, serving on the board of directors of and being an equity owner in Celsius Therapeutics Inc, and serving as a consultant to and being equity owner of Tango Therapeutics Inc. Dr Rossi reported serving as a consultant for Almirall, Merz, Dynamed, Canfield Scientific, Evolus, Biofrontera, Quantia MD, Lam Therapeutics, Regeneron, and Cutera; receiving travel support from Mavig and L’Oreal; serving on the advisory board for Allergan Inc and Skinfix; being founder of DAR Companies; receiving research grants from ASLMS: A Ward Memorial Research Grant and Skin Cancer Foundation; receiving research/study funding from Regen, LeoPharma, and Biofrontera; serving on the editorial boards of Lasers in Surgery and Medicine, Cutis, Journal of the American Academy of Dermatology, and Dermatologic Surgery; being a board member of ASDS; and being a committee member and/or chair for AAD, ASDS, and ASLMS. Dr Thomas reported serving as an advisory board committee member for Regeneron and Merck outside the submitted work. Dr Wong reported serving on the advisory board for Merck Pharmaceuticals, Bristol Myers Squibb, EMD Serona, Pfizer, Regeneron, and Castle Biosciences outside the submitted work. No other disclosures were reported.

Funding/Support: This article was partially supported by unrestricted research funding from the Section of Cutaneous Surgery in the Northwestern University Department of Dermatology. This research was funded, in part, by National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748 (to Dr Leitao).

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank Nobuo Arai, a patient representative who contributed his perspective based on personal experiences with extramammary Paget disease and helped shape the summary statements.

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AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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