European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 2. Treatment

Alexander J. Stratigos; Claus Garbe; Clio Dessinioti; Celeste Lebbe; Veronique Bataille; Lars Bastholt; Brigitte Dreno; Maria Concetta Fargnoli; Ana M. Forsea; Cecille Frenard; Catherine A. Harwood; Axel Hauschild; Christoph Hoeller; Lidija Kandolf-Sekulovic; Roland Kaufmann; Nicole W. J. Kelleners-Smeets; Josep Malvehy; Veronique del Marmol; Mark R. Middleton; David Moreno-Ramirez; Giovanni Pellecani; Ketty Peris; Philippe Saiag; Marieke H. J. van den Beuken-van Everdingen; Ricardo Vieira; Iris Zalaudek; Alexander M. M. Eggermont; Jean-Jacques Grob; European Dermatology Forum (EDF); European Association of Dermato-Oncology (EADO); European Organization for Research and Treatment of Cancer (EORTC)

doi:10.1016/j.ejca.2020.01.008

European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 2. Treatment

Alexander J. Stratigos^*, Claus Garbe, Clio Dessinioti, Celeste Lebbe, Veronique Bataille, Lars Bastholt, Brigitte Dreno, Maria Concetta Fargnoli, Ana M. Forsea, Cecille Frenard, Catherine A. Harwood, Axel Hauschild, Christoph Hoeller, Lidija Kandolf-Sekulovic, Roland Kaufmann, Nicole W. J. Kelleners-Smeets, Josep Malvehy, Veronique del Marmol, Mark R. Middleton, David Moreno-RamirezGiovanni Pellecani, Ketty Peris, Philippe Saiag, Marieke H. J. van den Beuken-van Everdingen, Ricardo Vieira, Iris Zalaudek, Alexander M. M. Eggermont, Jean-Jacques Grob, European Dermatology Forum (EDF), European Association of Dermato-Oncology (EADO), European Organization for Research and Treatment of Cancer (EORTC)

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

In order to update recommendations on treatment, supportive care, education and follow-up of patients with invasive cutaneous squamous cell carcinoma (cSCC), a multidisciplinary panel of experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer was formed. Recommendations were based on evidence-based literature review, guidelines and expert consensus. Treatment recommendations are presented for common primary cSCC (low risk, high risk), locally advanced cSCC, regional metastatic cSCC (operable or inoperable) and distant metastatic cSCC. For common primary cSCC (the most frequent cSCC type), first-line treatment is surgical excision with postoperative margin assessment or microscopically controlled sugery. Safety margins containing clinical normal-appearing tissue around the tumour during surgical excision and negative margins as reported in the pathology report are necessary to minimise the risk of local recurrence and metastasis. In case of positive margins, a re-excision shall be done, for operable cases. Lymph node dissection is recommended for cSCC with cytologically or histologically confirmed regional nodal involvement. Radiotherapy should be considered as curative treatment for inoperable cSCC, or for nonsurgical candidates. Anti-PD-1 antibodies are the first-line systemic treatment for patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or radiation, with cemiplimab being the first approved systemic agent for advanced cSCC by the Food and Drug Administration/European Medicines Agency. Second-line systemic treatments for advanced cSCC include epidermal growth factor receptor inhibitors (cetuximab) combined with chemotherapy or radiation therapy. Multidisciplinary board decisions are mandatory for all patients with advanced disease who require more than surgery. Patients should be engaged with informed decisions on management and be provided with best supportive care to optimise symptom management and improve quality of life. Frequency of follow-up visits and investigations for subsequent new cSCC depend on underlying risk characteristics. (C) 2020 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	83-102
Number of pages	20
Journal	European Journal of Cancer
Volume	128
DOIs	https://doi.org/10.1016/j.ejca.2020.01.008
Publication status	Published - Mar 2020

Keywords

Cutaneous squamous cell carcinoma
Locally advanced
Metastatic
Treatment
Surgical excision
Radiotherapy
Anti-PD-1 antibody
Cemiplimab
Chemotherapy
EGFR inhibitors
Follow-up
ORGAN TRANSPLANT RECIPIENTS
METASTATIC CUTANEOUS HEAD
ELECTIVE NECK DISSECTION
GROWTH-FACTOR RECEPTOR
IN-TRANSIT METASTASIS
CERVICAL LYMPH-NODES
PHASE-II
ADJUVANT RADIOTHERAPY
INTERFERON-ALPHA
INTRALESIONAL METHOTREXATE

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10.1016/j.ejca.2020.01.008

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Cite this

Stratigos, A. J., Garbe, C., Dessinioti, C., Lebbe, C., Bataille, V., Bastholt, L., Dreno, B., Fargnoli, M. C., Forsea, A. M., Frenard, C., Harwood, C. A., Hauschild, A., Hoeller, C., Kandolf-Sekulovic, L., Kaufmann, R., Kelleners-Smeets, N. W. J., Malvehy, J., del Marmol, V., Middleton, M. R., ... European Organization for Research and Treatment of Cancer (EORTC) (2020). European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 2. Treatment. European Journal of Cancer, 128, 83-102. https://doi.org/10.1016/j.ejca.2020.01.008

@article{5c762069c17c4ff3a9a12d3f5d0f5521,

title = "European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 2. Treatment",

abstract = "In order to update recommendations on treatment, supportive care, education and follow-up of patients with invasive cutaneous squamous cell carcinoma (cSCC), a multidisciplinary panel of experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer was formed. Recommendations were based on evidence-based literature review, guidelines and expert consensus. Treatment recommendations are presented for common primary cSCC (low risk, high risk), locally advanced cSCC, regional metastatic cSCC (operable or inoperable) and distant metastatic cSCC. For common primary cSCC (the most frequent cSCC type), first-line treatment is surgical excision with postoperative margin assessment or microscopically controlled sugery. Safety margins containing clinical normal-appearing tissue around the tumour during surgical excision and negative margins as reported in the pathology report are necessary to minimise the risk of local recurrence and metastasis. In case of positive margins, a re-excision shall be done, for operable cases. Lymph node dissection is recommended for cSCC with cytologically or histologically confirmed regional nodal involvement. Radiotherapy should be considered as curative treatment for inoperable cSCC, or for nonsurgical candidates. Anti-PD-1 antibodies are the first-line systemic treatment for patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or radiation, with cemiplimab being the first approved systemic agent for advanced cSCC by the Food and Drug Administration/European Medicines Agency. Second-line systemic treatments for advanced cSCC include epidermal growth factor receptor inhibitors (cetuximab) combined with chemotherapy or radiation therapy. Multidisciplinary board decisions are mandatory for all patients with advanced disease who require more than surgery. Patients should be engaged with informed decisions on management and be provided with best supportive care to optimise symptom management and improve quality of life. Frequency of follow-up visits and investigations for subsequent new cSCC depend on underlying risk characteristics. (C) 2020 Elsevier Ltd. All rights reserved.",

keywords = "Cutaneous squamous cell carcinoma, Locally advanced, Metastatic, Treatment, Surgical excision, Radiotherapy, Anti-PD-1 antibody, Cemiplimab, Chemotherapy, EGFR inhibitors, Follow-up, ORGAN TRANSPLANT RECIPIENTS, METASTATIC CUTANEOUS HEAD, ELECTIVE NECK DISSECTION, GROWTH-FACTOR RECEPTOR, IN-TRANSIT METASTASIS, CERVICAL LYMPH-NODES, PHASE-II, ADJUVANT RADIOTHERAPY, INTERFERON-ALPHA, INTRALESIONAL METHOTREXATE",

author = "Stratigos, \{Alexander J.\} and Claus Garbe and Clio Dessinioti and Celeste Lebbe and Veronique Bataille and Lars Bastholt and Brigitte Dreno and Fargnoli, \{Maria Concetta\} and Forsea, \{Ana M.\} and Cecille Frenard and Harwood, \{Catherine A.\} and Axel Hauschild and Christoph Hoeller and Lidija Kandolf-Sekulovic and Roland Kaufmann and Kelleners-Smeets, \{Nicole W. J.\} and Josep Malvehy and \{del Marmol\}, Veronique and Middleton, \{Mark R.\} and David Moreno-Ramirez and Giovanni Pellecani and Ketty Peris and Philippe Saiag and \{van den Beuken-van Everdingen\}, \{Marieke H. J.\} and Ricardo Vieira and Iris Zalaudek and Eggermont, \{Alexander M. M.\} and Jean-Jacques Grob and \{European Dermatology Forum (EDF)\} and \{European Association of Dermato-Oncology (EADO)\} and \{European Organization for Research and Treatment of Cancer (EORTC)\}",

note = "Funding Information: The development of the current set of guideline was supported solely by funds of the EADO which were used to mainly support the consensus meeting.Dr. Stratigos reports personal fees and/or research support from Novartis, Roche, BMS, AbbVie, Sanofi, Regeneron, Genesis Pharma, outside the submitted work. 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 Pierre Fabre, personal fees from Philogen, grants and personal fees from Roche, grants and personal fees from Sanofi, outside the submitted work. Dr. Dessinioti has nothing to disclose. Dr. Lebbe reports grants and personal fees from Bristol-Myers Squibb, personal fees from MSD, personal fees from Novartis, personal fees from Amgen, grants and personal fees from Roche, personal fees from Avantis Medical Systems, personal fees from Pierre Fabre, personal fees from Pfizer, personal fees from Incyte, outside the submitted work. Dr. Bataille reports personal fees from Novartis, personal fees from Merck MSD, outside the submitted work. Dr. Bastholt reports personal fees for advisory board activity: BMS, Roche, Novartis, Pierre Fabre, AstraZeneca, Incyte, MSD/Merck, Bayer. Dr. Dr{\'e}no reports grants and personal fees from BMS, personal fees from MSD, grants and personal fees from Roche, grants and personal fees from Fabre, grants and personal fees from Sanofi, outside the submitted work. Dr. Fargnoli reports grants and personal fees from Almirall, grants and personal fees from Leo Pharma, personal fees from Janssen, grants and personal fees from Novartis, personal fees from Lilly, grants and personal fees from Sanofi, personal fees from UCB, grants and personal fees from AbbVie, personal fees from Celgene, personal fees from Pierre Fabre, grants and personal fees from Galderma, personal fees from Mylan, personal fees from Medac Pharma, personal fees from Roche, personal fees from Sun Pharma, outside the submitted work. Dr. Forsea reports scientific consultant/speaker fee from Novartis, Leo Pharma, Solartium, Pierre Fabre, outside the submitted work. Dr. Frenard has nothing to disclose. Dr. Harwood reports institutional research grants and honoraria from Sanofi, Novartis, Merck, Pfizer, Galderma, Meda, Almirall, PellePharm, Leo Pharma, Ceries. Dr. Hauschild reports honoraria and/or research grants from Almirall, BMS, Roche, Novartis, Pierre Fabre, Sun Pharma, Merck Serono, Sanofi-Aventis, Regeneron, MSD/Merck, Philogen, OncoSec outside the submitted work. Dr. Hoeller reports grants and personal fees from Amgen, 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, personal fees from Incyte, outside the submitted work. Dr. Kandolf-Sekulovic reports speakers{\textquoteright} honoraria for Roche, Novartis, MSD, BMS, Janssen outside the submitted work. Dr. Kaufmann reports institutional research grants (clinical trials) from AbbVie, Amgen, Biontech, BMS, Celgene, Galderma, Janssen, Leo, Lilly, Merck, MSD, Novartis, Pierre Fabre, Pfizer, Regeneron, Roche, Wyeth. Advisory board and honoraria from Merz, Roche, Novartis. Dr. Kelleners-Smeets reports grants from Netherlands Organization for Health Research and Development, other from Janssen-Cilag, other from AbbVie, other from Galderma, outside the submitted work. Dr. Malvehy reports research grants from Almirall, ISDIN, Leo Pharma, Galderma, GSK, Cantabria; participation in advisory board meetings for Almirall, Sun Pharma, BMS, Roche, Novartis, Pierre Fabre. Dr. del Marmol reports personal fees from MSD, from BMS, personal fees from Sanofi, grants and personal fees from AbbVie, grants from Janssen, outside the submitted work. Dr. Middleton reports personal fees and/or grants from Amgen, Roche, AstraZeneca, GSK, Novartis, Immunocore, BMS, Eisai and Merck. Institutional funding from Millennium, Vertex, Pfizer, Regeneron, TC Biopharm, BioLineRx, Replimune, outside the submitted work. Dr. Moreno-Ram{\'i}rez has nothing to disclose. Dr. Pellecani reports grants from university of Modena and Reggio Emilia, during the conduct of the study; grants from Novartis, grants and personal fees from Almirall, grants from Leo Pharma, from null, outside the submitted work. Dr. Peris reports honoraria for advisory board and grants from AbbVie, Almirall, Biogen Celgene, Lilly, Galderma, Leo Pharma, Novartis, Roche, Sanofi, Sun Pharma, Sandoz outside the submitted work. Dr. Saiag reports honoraria for advisory board and grants from Amgen, Bristol-Myers Squibb, MSD, Merck Serono, Novartis, Pfizer, Roche-Genentech, Pierre Fabre, and Sanofi, outside the submitted work. Dr. van den Beuken-van Everdingen has nothing to disclose. Dr. Vieira has nothing to disclose. Dr. Zalaudek reports honoraria and advisory board and grants from Sanofi, Sun Pharma, Novartis, Galderma, Roche, Celgene, Almirall, Leo Pharma, Mylan, Difa Cooper, Cieffe Labs, La Roche Posay, Pierre Fabre. Dr. Eggermont reports over the last 5 years personal fees as a consultant advisor for BIOCAD, BioInvent, Bristol-Myers Squibb (BMS), CatalYm, Ellipses, GlaxoSmithKline (GSK), HalioDx, Incyte, IO Biotech, ISA Pharmaceuticals, Merck Sharpe \& Dohme (MSD), Novartis, Pfizer, Polynoma, Regeneron, Sanofi, SELLAS, SkylineDx. Dr. Grob reports personal fees for advisory board and as speaker from Amgen, Roche, GSK, Novartis, BMS, Pierre Fabre, Merck, Sanofi, Merck, Pfizer outside the submitted work. Funding Information: Dr. Stratigos reports personal fees and/or research support from Novartis, Roche, BMS, AbbVie, Sanofi, Regeneron, Genesis Pharma, outside the submitted work. 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 Pierre Fabre, personal fees from Philogen, grants and personal fees from Roche , grants and personal fees from Sanofi , outside the submitted work. Dr. Dessinioti has nothing to disclose. Dr. Lebbe reports grants and personal fees from Bristol-Myers Squibb , personal fees from MSD, personal fees from Novartis, personal fees from Amgen, grants and personal fees from Roche , personal fees from Avantis Medical Systems, personal fees from Pierre Fabre, personal fees from Pfizer, personal fees from Incyte, outside the submitted work. Dr. Bataille reports personal fees from Novartis, personal fees from Merck MSD, outside the submitted work. Dr. Bastholt reports personal fees for advisory board activity: BMS, Roche, Novartis, Pierre Fabre, AstraZeneca, Incyte, MSD/Merck, Bayer. Dr. Dr{\'e}no reports grants and personal fees from BMS , personal fees from MSD, grants and personal fees from Roche , grants and personal fees from Fabre , grants and personal fees from Sanofi , outside the submitted work. Dr. Fargnoli reports grants and personal fees from Almirall , grants and personal fees from Leo Pharma , personal fees from Janssen, grants and personal fees from Novartis , personal fees from Lilly, grants and personal fees from Sanofi , personal fees from UCB, grants and personal fees from AbbVie , personal fees from Celgene, personal fees from Pierre Fabre, grants and personal fees from Galderma , personal fees from Mylan, personal fees from Medac Pharma, personal fees from Roche, personal fees from Sun Pharma, outside the submitted work. Dr. Forsea reports scientific consultant/speaker fee from Novartis, Leo Pharma, Solartium, Pierre Fabre, outside the submitted work. Dr. Frenard has nothing to disclose. Dr. Harwood reports institutional research grants and honoraria from Sanofi , Novartis , Merck , Pfizer , Galderma , Meda , Almirall , PellePharm , Leo Pharma , Ceries . Dr. Hauschild reports honoraria and/or research grants from Almirall , BMS , Roche , Novartis , Pierre Fabre , Sun Pharma , Merck Serono , Sanofi-Aventis , Regeneron , MSD/Merck , Philogen , OncoSec outside the submitted work. Dr. Hoeller reports grants and personal fees from Amgen , 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, personal fees from Incyte, outside the submitted work. Dr. Kandolf-Sekulovic reports speakers{\textquoteright} honoraria for Roche, Novartis, MSD, BMS, Janssen outside the submitted work. Dr. Kaufmann reports institutional research grants (clinical trials) from AbbVie , Amgen , Biontech , BMS , Celgene , Galderma , Janssen , Leo , Lilly , Merck , MSD , Novartis , Pierre Fabre , Pfizer , Regeneron , Roche , Wyeth . Advisory board and honoraria from Merz, Roche, Novartis. Dr. Kelleners-Smeets reports grants from Netherlands Organization for Health Research and Development , other from Janssen-Cilag, other from AbbVie, other from Galderma, outside the submitted work. Dr. Malvehy reports research grants from Almirall , ISDIN , Leo Pharma , Galderma , GSK , Cantabria ; participation in advisory board meetings for Almirall, Sun Pharma, BMS, Roche, Novartis, Pierre Fabre. Dr. del Marmol reports personal fees from MSD, from BMS, personal fees from Sanofi, grants and personal fees from AbbVie, grants from Janssen , outside the submitted work. Dr. Middleton reports personal fees and/or grants from Amgen , Roche , AstraZeneca , GSK , Novartis , Immunocore , BMS , Eisai and Merck . Institutional funding from Millennium , Vertex , Pfizer , Regeneron , TC Biopharm , BioLineRx , Replimune , outside the submitted work. Dr. Moreno-Ram{\'i}rez has nothing to disclose. Dr. Pellecani reports grants from university of Modena and Reggio Emilia , during the conduct of the study; grants from Novartis , grants and personal fees from Almirall , grants from Leo Pharma , from null, outside the submitted work. Dr. Peris reports honoraria for advisory board and grants from AbbVie , Almirall , Biogen Celgene , Lilly , Galderma , Leo Pharma , Novartis , Roche , Sanofi , Sun Pharma , Sandoz outside the submitted work. Dr. Saiag reports honoraria for advisory board and grants from Amgen , Bristol-Myers Squibb , MSD , Merck Serono , Novartis , Pfizer , Roche-Genentech , Pierre Fabre , and Sanofi , outside the submitted work. Dr. van den Beuken-van Everdingen has nothing to disclose. Dr. Vieira has nothing to disclose. Dr. Zalaudek reports honoraria and advisory board and grants from Sanofi , Sun Pharma , Novartis , Galderma , Roche , Celgene , Almirall , Leo Pharma , Mylan , Difa Cooper , Cieffe Labs , La Roche Posay , Pierre Fabre . Dr. Eggermont reports over the last 5 years personal fees as a consultant advisor for BIOCAD, BioInvent, Bristol-Myers Squibb (BMS), CatalYm, Ellipses, GlaxoSmithKline (GSK), HalioDx, Incyte, IO Biotech, ISA Pharmaceuticals, Merck Sharpe \& Dohme (MSD), Novartis, Pfizer, Polynoma, Regeneron, Sanofi, SELLAS, SkylineDx. Dr. Grob reports personal fees for advisory board and as speaker from Amgen, Roche, GSK, Novartis, BMS, Pierre Fabre, Merck, Sanofi, Merck, Pfizer outside the submitted work. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",

year = "2020",

month = mar,

doi = "10.1016/j.ejca.2020.01.008",

language = "English",

volume = "128",

pages = "83--102",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Ltd",

}

Stratigos, AJ, Garbe, C, Dessinioti, C, Lebbe, C, Bataille, V, Bastholt, L, Dreno, B, Fargnoli, MC, Forsea, AM, Frenard, C, Harwood, CA, Hauschild, A, Hoeller, C, Kandolf-Sekulovic, L, Kaufmann, R, Kelleners-Smeets, NWJ, Malvehy, J, del Marmol, V, Middleton, MR, Moreno-Ramirez, D, Pellecani, G, Peris, K, Saiag, P, van den Beuken-van Everdingen, MHJ, Vieira, R, Zalaudek, I, Eggermont, AMM, Grob, J-J, European Dermatology Forum (EDF), European Association of Dermato-Oncology (EADO) & European Organization for Research and Treatment of Cancer (EORTC) 2020, 'European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 2. Treatment', European Journal of Cancer, vol. 128, pp. 83-102. https://doi.org/10.1016/j.ejca.2020.01.008

TY - JOUR

T1 - European interdisciplinary guideline on invasive squamous cell carcinoma of the skin

T2 - Part 2. Treatment

AU - Stratigos, Alexander J.

AU - Garbe, Claus

AU - Dessinioti, Clio

AU - Lebbe, Celeste

AU - Bataille, Veronique

AU - Bastholt, Lars

AU - Dreno, Brigitte

AU - Fargnoli, Maria Concetta

AU - Forsea, Ana M.

AU - Frenard, Cecille

AU - Harwood, Catherine A.

AU - Hauschild, Axel

AU - Hoeller, Christoph

AU - Kandolf-Sekulovic, Lidija

AU - Kaufmann, Roland

AU - Kelleners-Smeets, Nicole W. J.

AU - Malvehy, Josep

AU - del Marmol, Veronique

AU - Middleton, Mark R.

AU - Moreno-Ramirez, David

AU - Pellecani, Giovanni

AU - Peris, Ketty

AU - Saiag, Philippe

AU - van den Beuken-van Everdingen, Marieke H. J.

AU - Vieira, Ricardo

AU - Zalaudek, Iris

AU - Eggermont, Alexander M. M.

AU - Grob, Jean-Jacques

AU - European Dermatology Forum (EDF)

AU - European Association of Dermato-Oncology (EADO)

AU - European Organization for Research and Treatment of Cancer (EORTC)

N1 - Funding Information: The development of the current set of guideline was supported solely by funds of the EADO which were used to mainly support the consensus meeting.Dr. Stratigos reports personal fees and/or research support from Novartis, Roche, BMS, AbbVie, Sanofi, Regeneron, Genesis Pharma, outside the submitted work. 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 Pierre Fabre, personal fees from Philogen, grants and personal fees from Roche, grants and personal fees from Sanofi, outside the submitted work. Dr. Dessinioti has nothing to disclose. Dr. Lebbe reports grants and personal fees from Bristol-Myers Squibb, personal fees from MSD, personal fees from Novartis, personal fees from Amgen, grants and personal fees from Roche, personal fees from Avantis Medical Systems, personal fees from Pierre Fabre, personal fees from Pfizer, personal fees from Incyte, outside the submitted work. Dr. Bataille reports personal fees from Novartis, personal fees from Merck MSD, outside the submitted work. Dr. Bastholt reports personal fees for advisory board activity: BMS, Roche, Novartis, Pierre Fabre, AstraZeneca, Incyte, MSD/Merck, Bayer. Dr. Dréno reports grants and personal fees from BMS, personal fees from MSD, grants and personal fees from Roche, grants and personal fees from Fabre, grants and personal fees from Sanofi, outside the submitted work. Dr. Fargnoli reports grants and personal fees from Almirall, grants and personal fees from Leo Pharma, personal fees from Janssen, grants and personal fees from Novartis, personal fees from Lilly, grants and personal fees from Sanofi, personal fees from UCB, grants and personal fees from AbbVie, personal fees from Celgene, personal fees from Pierre Fabre, grants and personal fees from Galderma, personal fees from Mylan, personal fees from Medac Pharma, personal fees from Roche, personal fees from Sun Pharma, outside the submitted work. Dr. Forsea reports scientific consultant/speaker fee from Novartis, Leo Pharma, Solartium, Pierre Fabre, outside the submitted work. Dr. Frenard has nothing to disclose. Dr. Harwood reports institutional research grants and honoraria from Sanofi, Novartis, Merck, Pfizer, Galderma, Meda, Almirall, PellePharm, Leo Pharma, Ceries. Dr. Hauschild reports honoraria and/or research grants from Almirall, BMS, Roche, Novartis, Pierre Fabre, Sun Pharma, Merck Serono, Sanofi-Aventis, Regeneron, MSD/Merck, Philogen, OncoSec outside the submitted work. Dr. Hoeller reports grants and personal fees from Amgen, 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, personal fees from Incyte, outside the submitted work. Dr. Kandolf-Sekulovic reports speakers’ honoraria for Roche, Novartis, MSD, BMS, Janssen outside the submitted work. Dr. Kaufmann reports institutional research grants (clinical trials) from AbbVie, Amgen, Biontech, BMS, Celgene, Galderma, Janssen, Leo, Lilly, Merck, MSD, Novartis, Pierre Fabre, Pfizer, Regeneron, Roche, Wyeth. Advisory board and honoraria from Merz, Roche, Novartis. Dr. Kelleners-Smeets reports grants from Netherlands Organization for Health Research and Development, other from Janssen-Cilag, other from AbbVie, other from Galderma, outside the submitted work. Dr. Malvehy reports research grants from Almirall, ISDIN, Leo Pharma, Galderma, GSK, Cantabria; participation in advisory board meetings for Almirall, Sun Pharma, BMS, Roche, Novartis, Pierre Fabre. Dr. del Marmol reports personal fees from MSD, from BMS, personal fees from Sanofi, grants and personal fees from AbbVie, grants from Janssen, outside the submitted work. Dr. Middleton reports personal fees and/or grants from Amgen, Roche, AstraZeneca, GSK, Novartis, Immunocore, BMS, Eisai and Merck. Institutional funding from Millennium, Vertex, Pfizer, Regeneron, TC Biopharm, BioLineRx, Replimune, outside the submitted work. Dr. Moreno-Ramírez has nothing to disclose. Dr. Pellecani reports grants from university of Modena and Reggio Emilia, during the conduct of the study; grants from Novartis, grants and personal fees from Almirall, grants from Leo Pharma, from null, outside the submitted work. Dr. Peris reports honoraria for advisory board and grants from AbbVie, Almirall, Biogen Celgene, Lilly, Galderma, Leo Pharma, Novartis, Roche, Sanofi, Sun Pharma, Sandoz outside the submitted work. Dr. Saiag reports honoraria for advisory board and grants from Amgen, Bristol-Myers Squibb, MSD, Merck Serono, Novartis, Pfizer, Roche-Genentech, Pierre Fabre, and Sanofi, outside the submitted work. Dr. van den Beuken-van Everdingen has nothing to disclose. Dr. Vieira has nothing to disclose. Dr. Zalaudek reports honoraria and advisory board and grants from Sanofi, Sun Pharma, Novartis, Galderma, Roche, Celgene, Almirall, Leo Pharma, Mylan, Difa Cooper, Cieffe Labs, La Roche Posay, Pierre Fabre. Dr. Eggermont reports over the last 5 years personal fees as a consultant advisor for BIOCAD, BioInvent, Bristol-Myers Squibb (BMS), CatalYm, Ellipses, GlaxoSmithKline (GSK), HalioDx, Incyte, IO Biotech, ISA Pharmaceuticals, Merck Sharpe & Dohme (MSD), Novartis, Pfizer, Polynoma, Regeneron, Sanofi, SELLAS, SkylineDx. Dr. Grob reports personal fees for advisory board and as speaker from Amgen, Roche, GSK, Novartis, BMS, Pierre Fabre, Merck, Sanofi, Merck, Pfizer outside the submitted work. Funding Information: Dr. Stratigos reports personal fees and/or research support from Novartis, Roche, BMS, AbbVie, Sanofi, Regeneron, Genesis Pharma, outside the submitted work. 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 Pierre Fabre, personal fees from Philogen, grants and personal fees from Roche , grants and personal fees from Sanofi , outside the submitted work. Dr. Dessinioti has nothing to disclose. Dr. Lebbe reports grants and personal fees from Bristol-Myers Squibb , personal fees from MSD, personal fees from Novartis, personal fees from Amgen, grants and personal fees from Roche , personal fees from Avantis Medical Systems, personal fees from Pierre Fabre, personal fees from Pfizer, personal fees from Incyte, outside the submitted work. Dr. Bataille reports personal fees from Novartis, personal fees from Merck MSD, outside the submitted work. Dr. Bastholt reports personal fees for advisory board activity: BMS, Roche, Novartis, Pierre Fabre, AstraZeneca, Incyte, MSD/Merck, Bayer. Dr. Dréno reports grants and personal fees from BMS , personal fees from MSD, grants and personal fees from Roche , grants and personal fees from Fabre , grants and personal fees from Sanofi , outside the submitted work. Dr. Fargnoli reports grants and personal fees from Almirall , grants and personal fees from Leo Pharma , personal fees from Janssen, grants and personal fees from Novartis , personal fees from Lilly, grants and personal fees from Sanofi , personal fees from UCB, grants and personal fees from AbbVie , personal fees from Celgene, personal fees from Pierre Fabre, grants and personal fees from Galderma , personal fees from Mylan, personal fees from Medac Pharma, personal fees from Roche, personal fees from Sun Pharma, outside the submitted work. Dr. Forsea reports scientific consultant/speaker fee from Novartis, Leo Pharma, Solartium, Pierre Fabre, outside the submitted work. Dr. Frenard has nothing to disclose. Dr. Harwood reports institutional research grants and honoraria from Sanofi , Novartis , Merck , Pfizer , Galderma , Meda , Almirall , PellePharm , Leo Pharma , Ceries . Dr. Hauschild reports honoraria and/or research grants from Almirall , BMS , Roche , Novartis , Pierre Fabre , Sun Pharma , Merck Serono , Sanofi-Aventis , Regeneron , MSD/Merck , Philogen , OncoSec outside the submitted work. Dr. Hoeller reports grants and personal fees from Amgen , 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, personal fees from Incyte, outside the submitted work. Dr. Kandolf-Sekulovic reports speakers’ honoraria for Roche, Novartis, MSD, BMS, Janssen outside the submitted work. Dr. Kaufmann reports institutional research grants (clinical trials) from AbbVie , Amgen , Biontech , BMS , Celgene , Galderma , Janssen , Leo , Lilly , Merck , MSD , Novartis , Pierre Fabre , Pfizer , Regeneron , Roche , Wyeth . Advisory board and honoraria from Merz, Roche, Novartis. Dr. Kelleners-Smeets reports grants from Netherlands Organization for Health Research and Development , other from Janssen-Cilag, other from AbbVie, other from Galderma, outside the submitted work. Dr. Malvehy reports research grants from Almirall , ISDIN , Leo Pharma , Galderma , GSK , Cantabria ; participation in advisory board meetings for Almirall, Sun Pharma, BMS, Roche, Novartis, Pierre Fabre. Dr. del Marmol reports personal fees from MSD, from BMS, personal fees from Sanofi, grants and personal fees from AbbVie, grants from Janssen , outside the submitted work. Dr. Middleton reports personal fees and/or grants from Amgen , Roche , AstraZeneca , GSK , Novartis , Immunocore , BMS , Eisai and Merck . Institutional funding from Millennium , Vertex , Pfizer , Regeneron , TC Biopharm , BioLineRx , Replimune , outside the submitted work. Dr. Moreno-Ramírez has nothing to disclose. Dr. Pellecani reports grants from university of Modena and Reggio Emilia , during the conduct of the study; grants from Novartis , grants and personal fees from Almirall , grants from Leo Pharma , from null, outside the submitted work. Dr. Peris reports honoraria for advisory board and grants from AbbVie , Almirall , Biogen Celgene , Lilly , Galderma , Leo Pharma , Novartis , Roche , Sanofi , Sun Pharma , Sandoz outside the submitted work. Dr. Saiag reports honoraria for advisory board and grants from Amgen , Bristol-Myers Squibb , MSD , Merck Serono , Novartis , Pfizer , Roche-Genentech , Pierre Fabre , and Sanofi , outside the submitted work. Dr. van den Beuken-van Everdingen has nothing to disclose. Dr. Vieira has nothing to disclose. Dr. Zalaudek reports honoraria and advisory board and grants from Sanofi , Sun Pharma , Novartis , Galderma , Roche , Celgene , Almirall , Leo Pharma , Mylan , Difa Cooper , Cieffe Labs , La Roche Posay , Pierre Fabre . Dr. Eggermont reports over the last 5 years personal fees as a consultant advisor for BIOCAD, BioInvent, Bristol-Myers Squibb (BMS), CatalYm, Ellipses, GlaxoSmithKline (GSK), HalioDx, Incyte, IO Biotech, ISA Pharmaceuticals, Merck Sharpe & Dohme (MSD), Novartis, Pfizer, Polynoma, Regeneron, Sanofi, SELLAS, SkylineDx. Dr. Grob reports personal fees for advisory board and as speaker from Amgen, Roche, GSK, Novartis, BMS, Pierre Fabre, Merck, Sanofi, Merck, Pfizer outside the submitted work. Publisher Copyright: © 2020 Elsevier Ltd

PY - 2020/3

Y1 - 2020/3

N2 - In order to update recommendations on treatment, supportive care, education and follow-up of patients with invasive cutaneous squamous cell carcinoma (cSCC), a multidisciplinary panel of experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer was formed. Recommendations were based on evidence-based literature review, guidelines and expert consensus. Treatment recommendations are presented for common primary cSCC (low risk, high risk), locally advanced cSCC, regional metastatic cSCC (operable or inoperable) and distant metastatic cSCC. For common primary cSCC (the most frequent cSCC type), first-line treatment is surgical excision with postoperative margin assessment or microscopically controlled sugery. Safety margins containing clinical normal-appearing tissue around the tumour during surgical excision and negative margins as reported in the pathology report are necessary to minimise the risk of local recurrence and metastasis. In case of positive margins, a re-excision shall be done, for operable cases. Lymph node dissection is recommended for cSCC with cytologically or histologically confirmed regional nodal involvement. Radiotherapy should be considered as curative treatment for inoperable cSCC, or for nonsurgical candidates. Anti-PD-1 antibodies are the first-line systemic treatment for patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or radiation, with cemiplimab being the first approved systemic agent for advanced cSCC by the Food and Drug Administration/European Medicines Agency. Second-line systemic treatments for advanced cSCC include epidermal growth factor receptor inhibitors (cetuximab) combined with chemotherapy or radiation therapy. Multidisciplinary board decisions are mandatory for all patients with advanced disease who require more than surgery. Patients should be engaged with informed decisions on management and be provided with best supportive care to optimise symptom management and improve quality of life. Frequency of follow-up visits and investigations for subsequent new cSCC depend on underlying risk characteristics. (C) 2020 Elsevier Ltd. All rights reserved.

AB - In order to update recommendations on treatment, supportive care, education and follow-up of patients with invasive cutaneous squamous cell carcinoma (cSCC), a multidisciplinary panel of experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer was formed. Recommendations were based on evidence-based literature review, guidelines and expert consensus. Treatment recommendations are presented for common primary cSCC (low risk, high risk), locally advanced cSCC, regional metastatic cSCC (operable or inoperable) and distant metastatic cSCC. For common primary cSCC (the most frequent cSCC type), first-line treatment is surgical excision with postoperative margin assessment or microscopically controlled sugery. Safety margins containing clinical normal-appearing tissue around the tumour during surgical excision and negative margins as reported in the pathology report are necessary to minimise the risk of local recurrence and metastasis. In case of positive margins, a re-excision shall be done, for operable cases. Lymph node dissection is recommended for cSCC with cytologically or histologically confirmed regional nodal involvement. Radiotherapy should be considered as curative treatment for inoperable cSCC, or for nonsurgical candidates. Anti-PD-1 antibodies are the first-line systemic treatment for patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or radiation, with cemiplimab being the first approved systemic agent for advanced cSCC by the Food and Drug Administration/European Medicines Agency. Second-line systemic treatments for advanced cSCC include epidermal growth factor receptor inhibitors (cetuximab) combined with chemotherapy or radiation therapy. Multidisciplinary board decisions are mandatory for all patients with advanced disease who require more than surgery. Patients should be engaged with informed decisions on management and be provided with best supportive care to optimise symptom management and improve quality of life. Frequency of follow-up visits and investigations for subsequent new cSCC depend on underlying risk characteristics. (C) 2020 Elsevier Ltd. All rights reserved.

KW - Cutaneous squamous cell carcinoma

KW - Locally advanced

KW - Metastatic

KW - Treatment

KW - Surgical excision

KW - Radiotherapy

KW - Anti-PD-1 antibody

KW - Cemiplimab

KW - Chemotherapy

KW - EGFR inhibitors

KW - Follow-up

KW - ORGAN TRANSPLANT RECIPIENTS

KW - METASTATIC CUTANEOUS HEAD

KW - ELECTIVE NECK DISSECTION

KW - GROWTH-FACTOR RECEPTOR

KW - IN-TRANSIT METASTASIS

KW - CERVICAL LYMPH-NODES

KW - PHASE-II

KW - ADJUVANT RADIOTHERAPY

KW - INTERFERON-ALPHA

KW - INTRALESIONAL METHOTREXATE

U2 - 10.1016/j.ejca.2020.01.008

DO - 10.1016/j.ejca.2020.01.008

M3 - Article

C2 - 32113942

SN - 0959-8049

VL - 128

SP - 83

EP - 102

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 2. Treatment

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