Developments in the Treatment of Locally Advanced and Metastatic Squamous Cell Carcinoma of the Skin: A Rising Unmet Need

Abstract

Squamous cell carcinoma of the skin (SCCS) is a common malignancy with potentially devastating consequences in patients with locally advanced or metastatic disease. Its rising incidence, primarily a result of an aging population and increased ultraviolet (UV) radiation exposure, characterize an emerging unmet need. A firm understanding of the biology of this disease, likely distinct from that of other squamous malignancies because of the influence of UV radiation, is necessary in the evaluation of treatment paradigms. Careful recognition of high-risk features pertaining to tumor and host characteristics is paramount to proper management. However, a lack of standardization in guidelines in this regard creates a challenge for physicians. Questions persist regarding additional evaluation and treatment for advanced disease such as the roles for sentinel lymph node biopsy and the adjuvant use of radiation and chemotherapy. With respect to advanced disease, multiple combinations of chemotherapy have been tested with variable success, but no rigorous randomized studies have been conducted. In addition, EGFR inhibitors such as cetuximab and erlotinib have displayed antitumor activity and as such, warrant further investigation. In sum, the treatment of locally advanced and metastatic SCCS is a ripe area for clinical investigation. This article summarizes the current understanding of disease biology and emerging questions in the management of this disease.KEY POINTSGiven the increasing incidence of SCCS worldwide, there is a rising unmet need for new and effective treatments of locally advanced and metastatic disease.The disease biology of SCCS is likely distinct from other squamous malignancies and as such, trials specific for this tumor type are warranted to evaluate best clinical practices.Guidelines to aid the evaluation, surgical staging, and adjuvant treatment of high-risk disease need to be solidified with data from prospective trials.Studies conducted in the locally advanced and metastatic settings have been small, heterogeneous, and nonrandomized. As such, the opportunity exists to conduct rigorous studies to develop standards of care in this disease.Early reports of success with cetuximab and other EGFR inhibitors represent an exciting new opportunity for clinical trials, which are currently underway. Strategies for patient selection to optimize treatment response remain to be identified and are the subject of current and future studies.