The Multidisciplinary Management of Cutaneous Squamous Cell Carcinoma: A Comprehensive Review and Clinical Recommendations by a Panel of Experts
by
, , ,
Ignazio Stanganelli
1,2, 
Francesco Spagnolo
3,*, 
Giuseppe Argenziano
4
,
Paolo A. Ascierto
5,
Franco Bassetto
6, 
Paolo Bossi
7, 
Vittorio Donato
8,
Daniela Massi
9,
Cesare Massone
10, 
Roberto Patuzzo
11,
Giovanni Pellacani
12,
Pietro Quaglino
13, 
Paola Queirolo
14,
Iris Zalaudek
15,
Giuseppe Palmieri
16 and 
on behalf of Italian Melanoma Intergroup (IMI)
† 1
Skin Cancer Unit, Scientific Institute of Romagna for the Study of Cancer, IRCSS IRST, 47014 Meldola, Italy
2
Department of Dermatology, University of Parma, 43121 Parma, Italy
3
Deparment of Medical Oncology, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy
4
Dermatology Unit, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
5
Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy
6
Clinic of Plastic and Reconstructive Surgery, Padova University-Hospital, 35128 Padova, Italy
7
Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, ASST Spedali Civili of Brescia, University of Brescia, 25123 Brescia, Italy
8
Radiation Oncology Department, Azienda Ospedaliera San Camillo-Forlanini, 00152 Rome, Italy
9
Section of Anatomic Pathology, Department of Health Sciences, University of Florence, 50134 Florence, Italy
10
Dermatology Unit, Galliera Hospital, 16128 Genoa, Italy
11
Melanoma and Sarcoma Unit, Department of Surgery, IRCCS Fondazione Istituto Nazionale dei Tumori, 20133 Milan, Italy
12
Department of Dermatology, University of Modena and Reggio Emilia, 41124 Modena, Italy
13
Dermatology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
14
Division of Medical Oncology for Melanoma, Sarcoma and Rare Tumors, European Institute of Oncology IRCCS, 20141 Milan, Italy
15
Dermatology and Venereology Department, Ospedale Maggiore di Trieste, University of Trieste, 34125 Trieste, Italy
16
Unit of Cancer Genetics, Institute of Genetic and Biomedical Research (IRGB), National Research Council (CNR), 07100 Sassari, Italy
*
Author to whom correspondence should be addressed.
†
IMI includes the following additional members who participated as reviewers in this study and should be considered as coauthors: Ignazio Stanganelli (Meldola, Italy), Daniela Massi (Florence, Italy), Pietro Quaglino (Torino, Italy), Corrado Caracò (Naples, Italy), Virginia Ferraresi (Rome, Italy), Antonio M. Grimaldi (Benevento, Italy), Roberto Patuzzo (Milan, Italy), Giuseppe Palmieri (Sassari, Italy), Mario Mandalà (Perugia, Italy), Paola Queirolo (Milan, Italy).
Cancers 2022, 14(2), 377; https://doi.org/10.3390/cancers14020377
Submission received: 26 November 2021
/
Revised: 21 December 2021
/
Accepted: 29 December 2021
/
Published: 13 January 2022
(This article belongs to the Special Issue Keratinocyte Carcinomas: Biology and Evolving Non-Invasive Management Paradigms)
Simple Summary
Cutaneous squamous cell carcinoma is one of the most common forms of cancer. Although most cases are cured with surgical excision, a few tumors are associated with a high risk of local or distant relapse; therefore, it is relevant to identify high-risk lesions among all other low-risk CSCCs for the proper diagnostic and therapeutic management. Chemotherapy achieves mostly short-lived responses that do not lead to a curative effect and are associated with severe toxicities. Recently, PD-1 inhibitor cemiplimab was approved by the regulatory authorities for the treatment of advanced cutaneous squamous cell carcinoma; subsequently, the anti-PD-1 agent pembrolizumab received the approval by the FDA only in the same setting. Here, we provide a literature review and clinical recommendations by a panel of experts regarding the diagnosis, treatment, and follow-up of cutaneous squamous cell carcinoma.
Abstract
Cutaneous squamous cell carcinomas (CSCC) account for about 20% of all keratinocyte carcinomas, which are the most common form of cancer. Heterogeneity of treatments and low mortality are a challenge in obtaining accurate incidence data and consistent registration in cancer registries. Indeed, CSCC mostly presents as an indolent, low-risk lesion, with five-year cure rates greater than 90% after surgical excision, and only few tumors are associated with a high-risk of local or distant relapse; therefore, it is particularly relevant to identify high-risk lesions among all other low-risk CSCCs for the proper diagnostic and therapeutic management. Chemotherapy achieves mostly short-lived responses that do not lead to a curative effect and are associated with severe toxicities. Due to an etiopathogenesis largely relying on chronic UV radiation exposure, CSCC is among the tumors with the highest rate of somatic mutations, which are associated with increased response rates to immunotherapy. Thanks to such strong pre-clinical rationale, clinical trials led to the approval of anti-PD-1 cemiplimab by the FDA (Food and Drug Administration) and EMA (European Medicines Agency), and anti-PD-1 pembrolizumab by the FDA only. Here, we provide a literature review and clinical recommendations by a panel of experts regarding the diagnosis, treatment, and follow-up of CSCC.
