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Review
. 2022 Aug:171:203-231.
doi: 10.1016/j.ejca.2022.03.043. Epub 2022 Jun 19.

Diagnosis and treatment of Merkel cell carcinoma: European consensus-based interdisciplinary guideline - Update 2022

Marie-Léa Gauci  1 , Cynthia Aristei  2 , Jurgen C Becker  3 , Astrid Blom  4 , Veronique Bataille  5 , Brigitte Dreno  6 , Veronique Del Marmol  7 , Ana M Forsea  8 , Maria C Fargnoli  9 , Jean-Jacques Grob  10 , Fabio Gomes  11 , Axel Hauschild  12 , Christoph Hoeller  13 , Catherine Harwood  14 , Nicole Kelleners-Smeets  15 , Roland Kaufmann  16 , Aimilios Lallas  17 , Josep Malvehy  18 , David Moreno-Ramirez  19 , Ketty Peris  20 , Giovanni Pellacani  21 , Philippe Saiag  4 , Alexander J Stratigos  22 , Ricardo Vieira  23 , Iris Zalaudek  24 , Alexander C J van Akkooi  25 , Paul Lorigan  26 , Claus Garbe  27 , Céleste Lebbé  28 ; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC)
Affiliations
Free article
Review

Diagnosis and treatment of Merkel cell carcinoma: European consensus-based interdisciplinary guideline - Update 2022

Marie-Léa Gauci et al. Eur J Cancer. 2022 Aug.
Free article

Abstract

Merkel cell carcinoma (MCC) is a rare skin cancer, accounting for less than 1% of all cutaneous malignancies. It is found predominantly in white populations and risk factors include advanced age, ultraviolet exposure, male sex, immunosuppression, such as AIDS/HIV infection, haematological malignancies or solid organ transplantation, and Merkel cell polyomavirus infection. MCC is an aggressive tumour with 26% of cases presenting lymph node involvement at diagnosis and 8% with distant metastases. Five-year overall survival rates range between 48% and 63%. Two subsets of MCC have been characterised with distinct molecular pathogenetic pathways: ultraviolet-induced MCC versus virus-positive MCC, which carries a better prognosis. In both subtypes, there are alterations in the retinoblastoma protein and p53 gene structure and function. MCC typically manifests as a red nodule or plaque with fast growth, most commonly on sun exposed areas. Histopathology (small-cell neuroendocrine appearance) and immunohistochemistry (CK20 positivity and TTF-1 negativity) confirm the diagnosis. The current staging systems are the American Joint Committee on Cancer/Union for international Cancer control 8th edition. Baseline whole body imaging is encouraged to rule out regional and distant metastasis. For localised MCC, first-line treatment is surgical excision with postoperative margin assessment followed by adjuvant radiation therapy (RT). Sentinel lymph node biopsy is recommended in all patients with MCC without clinically detectable lymph nodes or distant metastasis. Adjuvant RT alone, eventually combined with complete lymph nodes dissection is proposed in case of micrometastatic nodal involvement. In case of macroscopic nodal involvement, the standard of care is complete lymph nodes dissection potentially followed by post-operative RT. Immunotherapy with anti-PD-(L)1 antibodies should be offered as first-line systemic treatment in advanced MCC. Chemotherapy can be used when patients fail to respond or are intolerant for anti-PD-(L)1 immunotherapy or clinical trials.

Keywords: Consensus; EDF; Guidelines; MCC; Merkel cell.

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Conflict of interest statement

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Celeste Lebbe reports AMGEN : Advisory Board, Advisory Role, Honoraria, Speaker’s Bureau, Bristol-Myers Squibb : Advisory Board, Advisory Role, Funding, Honoraria, Speaker’s Bureau, Travel, Accommodations, Expenses, Merck-Serono : Advisory Board, Advisory Role, MSD : Advisory Board, Advisory Role, Honoraria, Speaker’s Bureau, Travel, Accommodations, Expenses, Novartis: Advisory Board, Advisory Role, Honoraria, Speaker’s Bureau, Travel, Accommodations, Expenses, Pierre Fabre : Advisory Board, Advisory Role, Honoraria, Speaker’s Bureau, Travel, Accommodations, Expenses Roche : Advisory Board, Advisory Role, Funding, Honoraria, Speaker’s Bureau, Sanofi : Advisory Board, Advisory Role, Travel, Accommodations, Expenses Incyte : Honoraria Pfizer : Honoraria Marie-Léa Gauci – no conflicts declared. Cynthia Aristei – no conflicts declared J.C. Becker reports receiving speaker’s bureau honoraria from Amgen, Pfizer, Recordati and Sanofi, is a paid consultant/advisory board member/DSMB member for Almirall, Boehringer Ingelheim, InProTher, ICON, MerckSerono, Pfizer, 4SC, and Sanofi/Regeneron. His group receives research grants from Bristol-Myers Squibb, Merck Serono, HTG, IQVIA, and Alcedis. Speaker’s bureau honoraria from Amgen, Pfizer, Recordati and Sanofi; paid consultant/advisory/DSMB board member for Almirall, Boehringer Ingelheim, ICON, InProTher, MerckSerono, Pfizer, 4SC, and Sanofi/Regeneron. Research grants from Bristol-Myers Squibb, Merck Serono, HTG, IQVIA, and Alcedis. Astrid Blom – no conflicts declared Veronique Bataille – no conflicts declared Brigitte Dreno reports Merck Serono: board member Veronique Del marmol – no conflicts declared Ana Maria Forsea – no conflicts declared Maria Concetta Fargnoli – no conflicts declared Jean Jacques Grob reports Advisor for Merck, Pfizer, Novartis, BMS, MSD, Roche, Pierre Fabre, Amgen, Sanofi, Philogen Fabio Gomes – no conflicts declared Dr. Hauschild reports grants and personal fees from Amgen, grants and personal fees from BMS, grants and personal fees from Eisai, grants and personal fees from Immunocore, grants and personal fees from MerckPfizer, grants and personal fees from MSD/Merck, grants and personal fees from Novartis Pharma, grants and personal fees from Philogen, grants and personal fees from Pierre Fabre, grants and personal fees from Regeneron, grants and personal fees from Replimune, grants and personal fees from Roche, grants and personal fees from Sanofi-Genzyme, grants and personal fees from Seagen outside the submitted work. Christoph Hoeller reports grants and personal fees from Amgen, personal fees from Almirall, personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Pierre Fabre, personal fees from Roche, personal fees from Sanofi, outside the submitted work Catherine Harwood – no conflicts declared Dr. Kelleners-Smeets reports institutional research grants (clinical trials) from Galderma and Will Pharma, advisory board and speakers’ honoraria from Janssen-Cilag, Galderma, AbbVie, Leopharma, Sun Pharmaceutical, Novartis and MSD outside the submitted work. Roland Kaufmann – no conflicts declared Aimilios Lallas – no conflicts declared J Malvehy –reports personal fees from Amgen, personal fees from MSD, grants and personal fees from Novartis, grants and personal fees from Almirall, grants and personal fees from BMS, personal fees from Philogen, grants and personal fees from Roche, grants from Sanofi, personal fees from Sunpharma, personal fees from Pierre Fabre, outside the submitted work. David Moreno-Ramirez – no conflicts declared Ketty Peris reports: Almirall – personal fee – Advisory Board Lilly – personal fee – Advisory Board Galderma – personal fee – Advisory Board Leo Pharma – personal fee – Advisory Board, Pierre Fabre – personal fee – Advisory Board Novartis– personal fee – Advisory Board Sanofi – personal fee – Advisory Board Sun Pharma– personal fee – Advisory Board G Pellacani – no conflicts declared Philippe Saiag reports received consulting fees from Merk-Serono and MSD Dr. Stratigos reports personal fees from Sanofi, personal fees from Janssen CILAG, personal fees and non-financial support from Novartis, grants from Genesis Pharma, grants from Abbvie, grants and personal fees from BMS, personal fees from Regeneron, grants from Leo-Pharma, grants from Lilly, outside the submitted work Ricardo Vieira – no conflicts declared Iris Zalaudek reports MSD, Novartis, Sunpharma, Sanofi Genzyme, Regeneron, Philogen Alex Van Akkooi reports Advisory Board & Consultancy Honoraria: Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Sirius Medical, 4SC. All paid to institute and unrelated to current work. Research grants: Amgen & Merck-Pfizer. All paid to institute and unrelated to current work. Paul Lorigan – no conflicts declared Claus Garbe reports: Dr. Garbe reports personal fees from Amgen, personal fees from MSD, grants and personal fees from Novartis, grants and personal fees from NeraCare, grants and personal fees from BMS, personal fees from Philogen, grants and personal fees from Roche, grants and personal fees from Sanofi, outside the submitted work.

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