Abstract

Simple SummaryCutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer, which predominantly occurs on the head and neck. Early detection and treatment of primary tumours is crucial to limit progression and local invasion of deep tissues. While high-risk markers of poor prognosis have been identified, factors predicting regional control or survival remain uncertain. Therefore, diagnosis and management of cSCC should be performed individually, considering patient’s clinicopathological profile and the best available treatment options. Surgical excision, radiotherapy, and/or systemic treatments can be selected depending on patient’s status and tumour stage. Considering that a more comprehensive assessment will be provided by a multidisciplinary team, we aimed to generate a practical document that may assist oncologists and dermatologists on the prognosis, diagnosis, management, and follow-up of patients with advanced cSCC.Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer, the incidence of which has risen over the last years. Although cSCC rarely metastasizes, early detection and treatment of primary tumours are critical to limit progression and local invasion. Several prognostic factors related to patients’ clinicopathologic profile and tumour features have been identified as high-risk markers and included in the stratification scales, but their association with regional control or survival is uncertain. Therefore, decision-making on the diagnosis and management of cSCC should be made based on each individual patient’s characteristics. Recent advances in non-invasive imaging techniques and molecular testing have enhanced clinical diagnostic accuracy. Surgical excision is the mainstay of local treatment, whereas radiotherapy (RT) is recommended for patients with inoperable disease or in specific circumstances. Novel systemic treatments including immunotherapies and targeted therapies have changed the therapeutic landscape for cSCC. The anti-PD-1 agent cemiplimab is currently the only FDA/EMA-approved first-line therapy for patients with locally advanced or metastatic cSCC who are not candidates for curative surgery or RT. Given the likelihood of recurrence and the increased risk of developing multiple cSCC, close follow-up should be performed during the first years of treatment and continued long-term surveillance is warranted.

Highlights

  • Cutaneous squamous cell carcinoma is one of the most relevant non-melanoma skin cancers (NMSC), along with basal cell carcinoma (BCC)

  • To further support the evidence addressed and its applicability in clinical practice, a questionnaire was conducted among a multidisciplinary panel of specialists with the aim of providing consensus recommendations on the prognosis, diagnosis, treatment, and follow-up of Cutaneous squamous cell carcinoma (cSCC) (References [10,11,12] are cited in the Supplementary Material)

  • Assessment of Comorbidities In NMSC patients, three comorbidity assessment tools are frequently used in clinical trials and could be considered in clinical practice: the Charlson Comorbidity Index (CCI), the American Society of Anesthesiologists (ASA) risk classification system, and the Adult Comorbidity Evaluation-27 (ACE-27) [41]

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Summary

Introduction

Cutaneous squamous cell carcinoma (cSCC) is one of the most relevant non-melanoma skin cancers (NMSC), along with basal cell carcinoma (BCC). In Spain, cSCC is the second cause of skin cancer-related mortality, with an estimated incidence of 40 cases per 100,000 person-years [3]. It predominantly occurs on the head and neck (cSCCHN). Artificial ultraviolet radiation, including PUVA therapy with a load of more than 350 sessions, has been associated with a higher incidence of cSCC [5]. A broader therapeutic arsenal beyond surgery and RT is currently available that includes novel systemic treatments, such as new chemotherapeutic agents, targeted therapies, or immunotherapies [8,9]. To further support the evidence addressed and its applicability in clinical practice, a questionnaire was conducted among a multidisciplinary panel of specialists with the aim of providing consensus recommendations on the prognosis, diagnosis, treatment, and follow-up of cSCC (References [10,11,12] are cited in the Supplementary Material)

Tumour Staging and Prognostic Factors
Assessment of Comorbidities
Risk Stratification
Locoregional Assessment and Sentinel Node Biopsy
Local Treatment
Role of Radiotherapy
Targeted Therapy
Immunotherapy
Immunosuppressed Patients
Follow-Up and Monitoring
Findings
Summary and Conclusions
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