www.thelancet.com/oncology Vol 20 December 2019 e699 Policy Review Lancet Oncol 2019; 20: e699–714 *Authors contributed equally and are lead authors Department of Dermatology (J L Owen MD, B Worley MD, R C Kelm MD, J N Choi MD, K A Reynolds BA, E Poon PhD, Prof M Alam MD), Division of Hematology and Oncology, Department of Medicine (S Chandra MD), Department of Plastic Surgery (Prof J Kim MD), Department of Radiation Oncology (Prof B B Mittal MD), and Department of Otolaryngology—Head and Neck Surgery (Prof S Samant MD, Prof J R Thomas MD), Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Dermatology, Yale School of Medicine, New Haven, CT, USA (N Kibbi MD); Division of Dermatology (B Worley), Department of Pathology and Laboratory Medicine (S H Bradshaw MD), and The Ottawa Health Research Institute (T Ramsay PhD), The Ottawa Hospital, Ottawa, ON, Canada; Department of Dermatology and Cutaneous Biology (J V Wang MD) and Ocular Oncology Service, Wills Eye Hospital (Prof C L Shields MD), Thomas Jefferson University, Philadelphia, PA, USA; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA (C A Barker MD); Department of Dermatology, Saint Louis University School of Medicine, Saint Louis, MO, USA (R Behshad MD); Department of Dermatology (Prof C K Bichakjian MD) and Department of Ophthalmology and Visual Sciences, Kellogg Eye Center (H Demirci MD) University of Michigan, Sebaceous carcinoma: evidence-based clinical practice guidelines Joshua L Owen*, Nour Kibbi*, Brandon Worley*, Ryan C Kelm, Jordan V Wang, Christopher A Barker, Ramona Behshad, Christopher K Bichakjian, Diana Bolotin, Jeremy S Bordeaux, Scott H Bradshaw, Todd V Cartee, Sunandana Chandra, Nancy L Cho, Jennifer N Choi, M Laurin Council, Hakan Demirci, Daniel B Eisen, Bita Esmaeli, Nicholas Golda, Conway C Huang, Sherrif F Ibrahim, S Brian Jiang, John Kim, Timothy M Kuzel, Stephen Y Lai, Naomi Lawrence, Erica H Lee, Justin J Leitenberger, Ian A Maher, Margaret W Mann, Kira Minkis, Bharat B Mittal, Kishwer S Nehal, Isaac M Neuhaus, David M Ozog, Brian Petersen, Veronica Rotemberg, Sandeep Samant, Faramarz H Samie, Sabah Servaes, Carol L Shields, Thuzar M Shin, Joseph F Sobanko, Ally-Khan Somani, William G Stebbins, J Regan Thomas, Valencia D Thomas, David T Tse, Abigail H Waldman, Michael K Wong, Y Gloria Xu, Siegrid S Yu, Nathalie C Zeitouni, Timothy Ramsay, Kelly A Reynolds, Emily Poon, Murad Alam Sebaceous carcinoma usually occurs in adults older than 60 years, on the eyelid, head and neck, and trunk. In this Review, we present clinical care recommendations for sebaceous carcinoma, which were developed as a result of an expert panel evaluation of the fndings of a systematic review. Key conclusions were drawn and recommendations made for diagnosis, frst-line treatment, radiotherapy, and post-treatment care. For diagnosis, we concluded that deep biopsy is often required; furthermore, diferential diagnoses that mimic the condition can be excluded with special histological stains. For treatment, the recommended frst-line therapy is surgical removal, followed by margin assessment of the peripheral and deep tissue edges; conjunctival mapping biopsies can facilitate surgical planning. Radiotherapy can be considered for cases with nerve or lymph node involvement, and as the primary treatment in patients who are ineligible for surgery. Post-treatment clinical examination should occur every 6 months for at least 3 years. No specifc systemic therapies for advanced disease can be recommended, but targeted therapies and immunotherapies are being developed. Introduction Sebaceous carcinoma is an uncommon but potentially aggressive cutaneous malignancy. Periocular sebaceous carcinoma arises from the sebaceous glands, whereas extraocular sebaceous carcinoma has an indeterminate origin. Periocular and extraocular tumours behave diferently and have diferent genetic signatures. 1,2 No standardised treatment yet exists. In this Review, we present guidelines for the diagnosis and management of sporadic sebaceous carcinoma (panel 1; panel 2), based on expert assessment of data derived from a systematic review of the literature. Management of Muir-Torre syndrome—a variant of Lynch syndrome with cutaneous neoplasms—has been described elsewhere. Guideline development Experts in sebaceous carcinoma were identifed by JLO, BW, NK, and MA through relevant publication history, national clinical reputation, involvement in previous cancer guidelines, and peer nomination. Key stakeholder specialties were included. The panel was composed of people specialising in general dermatology (seven specialists), cutaneous oncology (29), ocular oncology (four), surgical oncology (three), medical oncology (three), dermatopathology (three), radiation oncology (two), general radiology (one), plastic surgery (one), statistics (one), and research methodology (three). The expert committee reviewed data tables extracted from the published literature to answer the question, “in individuals without a genetic predisposition, what are the best practices for diagnosis, risk assessment, and management of extraocular and periocular sebaceous carcinoma?” The consensus process was through teleconferences and an in-person meeting at the American Society for Dermatologic Surgery Annual Meeting in Phoenix, AZ, USA, in October, 2018. The guidelines were collaboratively revised in four rounds until consensus on key recom- mendations was achieved. All panellists reviewed the fnal manuscript. A fow diagram of the study screening process can be found in fgure 1. Grading of recommendations We graded recommendations in accordance with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group. We also reported National Comprehensive Cancer Network Evidence Grading and Consensus categories. For the purposes of these guidelines, recommendations with category 2A indicate unanimous consensus, whereas category 2B indicates at least 90% of the panel voted in favour of the recommendation. Guideline update plan These guidelines will be reviewed for revision every 5 years to ensure the recommendations refect up-to-date evidence. When new practice-changing studies emerge, an interim update might be issued. Method for calculating surgical margins Case-level data for presurgical and postsurgical margins were extracted, primarily from studies using margin- controlled techniques. Recurrent or incompletely excised cases were excluded. From the mean and standard deviation of the margin that resulted in complete tumour clearance, a Q–Q plot showed whether or not population- wide data would approximate a normal distribution.