Although most cSCCs are localized and can be easily treated, approximately 5% of patients will experience local recurrence, 4% will develop nodal metastases, and up to 2% will die of the disease.

In addition to the small but significant number of deaths attributed to cSCC each year, the disease and its associated precancerous skin lesions contribute to a large financial burden of more than $4.5 billion annually in the United States.

cSCC is a type of nonmelanoma skin cancer (NMSC), the most frequently diagnosed cancer in North America.4 In 2006, the estimated number of incident cases of NMSC in the United States was 4,013,890, and approximately 62% of affected individuals were treated for &ge;1 skin cancer.

In 2012, the estimated number of NMSCs in the United States was 5,434,193, and 3,315,554 individuals were treated.

Of these patients with NMSCs, there were estimated to be 1,027,700 cases of cSCC.

Individuals with lighter skin have been diagnosed with cSCCs at a significantly higher rate than those with darker skin types.

Several causes of cSCC have been described, such as ultraviolet (UV) radiation; ionizing radiation; genodermatoses; human papillomavirus (HPV); arsenic; polycyclic aromatic hydrocarbons; immunosuppression; chronic ulcer and chronic sinus tract; scar; and preexisting chronic dermatoses.

The most common cause of cSCC is UV exposure, with the majority of risk linked to ultraviolet B (290-320 nm) and additional risk from ultraviolet A (320-400 nm).

Individuals with light skin that burns with increasing UV exposure have the highest risk for developing skin cancer.

Individuals with a history of sun exposure throughout childhood, especially those with a history of sunburn, may have the highest risk. The risk for cSCC is approximately 3 times higher in individuals born in areas that receive high amounts of UV radiation compared with those who move to sun-exposed locales in adulthood. Additionally, the risk for cSCC is up to 5 times higher in individuals with light skin color, blue or hazel eyes, and red or blonde hair compared with those who have darker skin, eyes, and hair.10 Increased risk has also been established in individuals with freckling, solar elastosis, or facial telangiectasia.

Immunosuppression also contributes to the development of cSCC, particularly in the case of organ transplant recipients. Organ transplant recipients have approximately twice the overall risk for cancer, as compared with the general population.

In a nationwide study using Swedish registries, the risk for cSCC was increased 198-fold among heart and lung transplant recipients, 121-fold among kidney transplant recipients, and 32-fold among liver transplant recipients.

Actinic keratosis (AK) is the most common precursor of cSCC. AKs are typically 2 mm to 6 mm in diameter and are scaly lesions that are often more easily felt than seen, as they may be pink, brown, or the same color as the skin.

Individuals with multiple keratoses have a lifetime risk of 0.1% to 14% for developing cSCC.

This cumulative risk depends on both the number of lesions and the length of time that the lesions persist, as well as other high-risk factors, such as prior radiation therapy, existing degree of photodamage, personal or familial history of skin cancer, Fitzpatrick skin type, and immunosuppression associated with disease or medications.

Bowenoid papulosis and epidermodysplasia verruciformis are other precancerous lesions that may develop into cSCC.

Bowenoid papulosis is often associated with HPV types 16 and 18.

Patients often present with hyperpigmented papules that have histologic features in line with Bowen&rsquo;s disease, which is a type of squamous cell carcinoma (SCC) in situ.

Epidermodysplasia verruciformis is a condition in which flat, widespread warts may degenerate into either carcinoma in situ or invasive SCC.

If not adequately treated, SCC in situ may progress to invasive disease.

Common forms of SCC in situ include Bowen disease and Erythroplasia of Queyrat.20 Patients with Bowen disease often present with erythematous, scaly, or velvety plaques on sun-exposed areas that are well demarcated.

Occurring on the glans penis of uncircumcised men, Erythroplasia of Queyrat is less common and presents as smooth, red plaques.

The most common locations for invasive cSCCs are the head and neck, followed by the trunk.

cSCC often presents as a scaly, erythematous papule with or without ulceration and hemorrhagic crust on chronically sun-exposed skin in older patients.

Pronounced hyperkeratosis may be present, and large lesions may contain a central core of hard keratin and hemorrhagic debris. Most lesions are asymptomatic; however, some lesions may bleed or be tender to the touch. Additionally, patients may describe cSCC lesions as painful or itchy nonhealing wounds that may bleed with trauma.

Upon presentation of cSCC, a physical examination and complete history should be taken, including information on sun exposure beginning in childhood, occupational exposure to UV light, prior radiation treatment, and possible causes of immunosuppression.

Patients with a history of skin cancer require screening to monitor for recurrence, persistence, or new lesions, because the risk for developing a second cSCC within 5 years following treatment of a first tumor is approximately 30%.

For staging purposes, cSCC was grouped with various other cutaneous malignancies until the seventh edition of the American Joint Committee on Cancer (AJCC) staging manual was published in 2010 and cSCC was specifically addressed.

Several studies have evaluated the use of this staging system for cSCC, noting unsatisfactory prognostication in different staging groups.

Based on results from a retrospective cohort study demonstrating that the majority of poor outcomes occurred in AJCC T2 tumors, an alternative tumor staging system was developed (Brigham and Women&rsquo;s Hospital [BWH] system).

The aim of the alternative staging system was to prognostically stratify the T2 group based on strongly predictive risk factors of at least 2 endpoints of interest. These risk factors include a tumor diameter of &ge;2 cm, poorly differentiated histologic characteristics, perineural invasion, and tumor invasion beyond the subcutaneous fat.

In this system, T1 tumors have no risk factors, T2a tumors have a single risk factor, T2b tumors have 2 to 3 risk factors, and T3 tumors have all 4 risk factors or bone invasion, coinciding with AJCC T3 and T4 cases.

Compared with the AJCC staging system, the BWH system does not address metastasis, nodal classifications, or advanced stage groups; however, the BWH system may provide improved prognostication for patients with localized cSCC.

These staging systems are compared in the TABLE.

Patients with tumors classified as T2a using the alternative staging system comprised 26% of the aforementioned retrospective study cohort and experienced rare poor outcomes. Five-year cumulative incidence was 6% for local recurrence, 4% for nodal metastasis, 0% for death from cSCC, and 24% for all-cause death, which together account for 16% of all cSCCrelated events.

Patients with tumors classified as T2b using the alternative staging system comprised 19% of the cohort and experienced significantly higher incidences of poor outcomes. Five-year cumulative incidence was 18% for local recurrence, 37% for nodal metastasis, 20% for death from cSCC, and 47% for all-cause death. Together, alternative stage T2a tumors accounted for 64% of all cSCC-related events including 43% of local recurrences, 72% of nodal metastases, and 83% of deaths from cSCC.

A study comparing the BWH staging system with the AJCC staging system validated the BWH system in a larger cohort of patients with cSCC.

Specifically, investigators reported that confidence intervals overlapped for AJCC T3 and T4 at all endpoints, demonstrating that these are not distinct stages, whereas BWH stages overlapped only slightly for the endpoint of overall death, demonstrating improved distinctiveness of all stages for the endpoints of local recurrence, nodal metastasis, and disease-specific death using BWH staging.

According to the findings, 86% of poor outcomes were reported in stages T1 and T2 using AJCC staging; however, using BWH staging, 40% of poor outcomes occurred in stages T1 and T2a, demonstrating a greater degree of homogeneity.

The authors also assessed monotonicity, which occurs when higher proportions of poor outcomes occur at higher tumor stages.

In AJCC staging, 14% of poor outcomes occurred in stages T3 and T4.

In BWH staging, however, 60% of poor outcomes occurred in stages T2b and T3, including 70% of nodal metastases and 83% of disease-specific deaths, demonstrating greater monotonicity.

Additional analyses evaluating upstaged and downstaged tumors using the BWH staging system compared with AJCC staging demonstrated that tumors downstaged by the BWH system to stage T1 and T2 have a low risk for poor outcomes, indicating appropriate downstaging.

Likewise, in the 86 cases upstaged from stage T1 and T2 in the AJCC staging system to stage T2b and T3 in the BWH staging system, there were 18 local recurrences, 18 nodal metastases, and 9 disease-specific deaths, indicating appropriate upstaging of these tumors based on poor outcomes.

The National Comprehensive Cancer Network (NCCN) has also described an approach for stratifying cSCC using risk factors.

This risk stratification is intended to give healthcare providers practical clinical guidance for treating cSCC, rather than accurate prognostication. It is based on a combination of available evidence and expert opinion.

The NCCN risk stratification is based on the clinical factors of tumor location and size; border definition; recurrence status; immunosuppression; prior site of radiation or chronic inflammation; growth rate; and presence of neurologic symptoms. Pathologic factors, including degree of differentiation, histologic subtype, depth, and perineural, lymphatic, or vascular involvement, are also used to determine risk for cSCC.

Currently, no evidence-based, optimal biopsy technique exists for sampling potential cSCC lesions.

Recommended biopsy techniques include shave biopsy, punch biopsy, and excisional biopsy. The purpose of excisional biopsy is to determine and confirm a cSCC diagnosis, whereas the purpose of excision with margins is to remove the tumor. For any biopsy method, the specimen size and depth should be adequate for providing clinical information and pathology details to allow for an accurate diagnosis and therapy guidance.

The selection of a specific biopsy technique is based on clinical characteristics of the tumor, patient-specific factors, patient preference, and physician judgment.

Clinical characteristics include morphology, expected histologic subtype and depth, natural history, and anatomic location. Patient-specific factors include bleeding and wound healing diatheses. Patient and physician preferences for minimizing biopsy-associated discomfort, trauma, infection risk, scar, or loss of function counterbalance the need to obtain information gleaned through biopsy.

These considerations are especially relevant on the head, neck, and other functional, sensory, or cosmetically sensitive sites. In the case of recurrent tumors, invasive tumors, or other aggressive tumor characteristics, additional biopsies or more extensive tissue resection may be required.

A presumptive cSCC diagnosis is attained through a physician&rsquo;s interpretation of clinical information (eg, appearance and morphology), anatomic location, and patientreported history.

Prior to treatment, the clinical diagnosis is routinely confirmed with biopsy findings. Along with biopsy tissue, additional information should be provided to the pathologist including patient age and gender; anatomic location; recurrence status; size of the lesion; immunosuppression status; and history related to radiation exposure, burns, and organ transplantation. The purpose of the pathology report is to convey an accurate diagnosis of the presence or absence of cSCC. In cases in which cSCC is detected, the degree of differentiation and any high- or low-risk features should be listed, including histologic subtype, depth of invasion, and the presence of perineural or lymphovascular invasion.

A dermatologist or pathologist with experience interpreting cutaneous neoplasms should perform the pathologic evaluation of skin biopsy specimens. These clinicians can best interpret clinical findings and histologic features of tumors, thus providing the most accurate and precise biopsy diagnosis.

Patients with large lesions (ie, &ge;2 cm in diameter) have reported local recurrence rates of 15% and metastatic rates of 30%, which are 2 and 3 times the recurrence rates and metastatic rates, respectively, among those with of smaller lesions.

Patients with large tumors (ie, &ge;2 cm in diameter) have 5-year cure rates of 58.3% to 74.8%%, whereas those with smaller tumors (ie, <2 cm in diameter) have 5-year cure rates of 83.5% to 98.1%.

Other clinical features that are associated with local recurrence and metastasis include immunosuppression, poor histologic differentiation, and previous treatment.

The rates of both local recurrence and metastasis are 47% for tumors with evidence of perineural involvement. Additionally, patients who are immunosuppressed have a cSCC metastasis rate of 12.9%. cSCCs of the lip and ear are aggressive lesions, with rates of recurrence and metastasis ranging between 10% and 19%.

Histologic features can also be used to predict recurrence and metastasis in patients with cSCCs. Predictive characteristics include involvement of the reticular dermis or subcutaneous fat, a depth of >4 mm, and penetration into muscle, cartilage, bone, or fascia.

Additionally, poorly differentiated cSCCs have been reported to have a recurrence rate of 28.6% and 5-year cure rates of 46.4% to 67.4%, whereas well-differentiated lesions have been reported to have a local recurrence rate of 13.6% and 5-year cure rates of 81.0% to 97.0%.

Conclusions cSCCs are the second most common form of skin cancer and are frequently caused by UV exposure. Although many tumors are localized, some may recur or metastasize. Early detection of precursor lesions, appropriate diagnosis, and staging of cSCCs is key to providing patients with appropriate prognostic information. Risk factors can be used for staging and predicting recurrence and metastasis.

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Engels EA, Pfeiffer RM, Fraumeni JF Jr, et al. Spectrum of cancer risk among US solid organ transplant recipients.

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Krynitz B, Edgren G, Lindel&ouml;f B, et al. Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008--a Swedish populationbased study.

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Clark JR, Rumcheva P, Veness MJ. Analysis and comparison of the 7th edition American Joint Committee on Cancer (AJCC) nodal staging system for metastatic cutaneous squamous cell carcinoma of the head and neck.

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Articles

Clinical Articles

Cutaneous squamous cell carcinoma is the second most common form of skin cancer, with an estimated 1 million cases treated in the United States each year.&nbsp;Although most cSCCs are localized and can be easily treated, approximately 5% of patients will experience local recurrence, 4% will develop nodal metastases, and up to 2% will die of the disease.&nbsp;In addition to the small but significant number of deaths attributed to cSCC each year, the disease and its associated precancerous skin lesions contribute to a large financial burden of more than $4.5 billion annually in the United States.

A Primer on the Epidemiology and Pathophysiology of Cutaneous Squamous Cell Carcinoma

A subset of patients with high-risk tumors, such as those who experience local recurrence and nodal metastases, has driven development within the therapeutic landscape that has resulted in the recent FDA approval of the first agent for the treatment of cSCC.

Moreover, development continues on other investigational agents, which, if approved, would give patients more therapeutic options and also potentially decrease the large financial burden of this common cancer.

Standard excision using &ldquo;bread loaf&rdquo; histopathologic sectioning requires a margin of skin that appears to be clinically normal around the tumor and surrounding erythema, to ensure complete removal of the cSCC with histologically negative margins.

The National Comprehensive Cancer Network guidelines recommend standard excision, using clinical margins of 4 mm to 6 mm as a primary treatment for localized, low-risk cSCC.

An expert work group agrees with the use of standard excision with a 4 mm to 6 mm margin of uninvolved skin around the biopsy site and tumor, extending down to mid-subcutaneous adipose tissue for histologic margin assessment in patients with low-risk primary cSCC.

Although standard excision may be considered for highrisk tumors, complete margin assessment is recommended prior to selecting a treatment modality.

If standard excision is performed on high-risk tumors, clinicians should consider the use of a linear repair, skin graft, or healing by second intention.

Importantly, closure should be delayed until confirmation of negative histologic margins, especially in cases of repair that require significant tissue rearrangement.

A systematic review and pooled analysis of 12 studies reported an overall local recurrence of 5.4% during followup after surgical excision.

These studies used inconsistent surgical margins, ranging from 2 mm to >10 mm, with some decisions regarding excision margins based on clinical diagnosis and surgeon preference.

Overall, authors reported a pooled average estimate of 8.8% for the frequency of incomplete surgical excisions.

The use of chemosurgery was first described for the removal of recurrent or difficult-to-treat cutaneous tumors in the 1940s.

This method was updated approximately 30 years later to eliminate the use of zinc chloride fixative paste (which contributed to patient discomfort), and to improve conservation of tissue by mitigating fixation beyond surgical margins and decreasing the amount of time required for the procedure.

This technique, referred to as microscopically controlled excision, involved injection with 1% lidocaine with epinephrine into the area of suspected tumor, which was then curetted. An excision of tissue approximately 3 mm to 5 mm thick was taken from the tumor bed, extending an additional 1 mm to 3 mm around the periphery of the wound. The tissue was briefly fixed in formaldehyde solution, and sections were mounted and stained for examination.

This technique was successful. Of the 102 lesions treated, only 3 recurrences were reported during a follow-up of 3 to 5 years for 76 tumors, and 5 to 8 years for 26 tumors. These recurrences were reported within 12 months, retreated, and were followed without reports of additional recurrence.

Following these reports, the use of MMS expanded, and appropriate-use criteria for MMS were published in 2012.

A systematic review reported that for primary cSCC treated with MMS, the 5-year local recurrence rate was 3.1%, whereas the 5-year local recurrence rates with C&E, surgical excision, and radiation therapy were 3.7%, 8.1%, and 10.0%, respectively.

Upon consideration of high-risk characteristics, the cure rate with MMS was 74.8% for tumors &ge;2 cm and 67.4% for poorly differentiated tumors, compared with 58.3% and 46.4%, respectively, with non-Mohs modalities.

The 5-year rates for locally recurrent cSCC were reported to be 10.0% for cSCC treated with MMS and 23.3% for cSCC treated with surgical excision.

MMS has been recommended for the treatment of high-risk cSCC.

C&E is regularly used for the treatment of low-risk cSCC and can be considered for the treatment of small, low-risk, primary cSCC, as well.

A pooled analysis demonstrated a recurrence rate of 1.7% following treatment with C&E.

A study of 257 basal cell carcinomas (BCCs) revealed no major cosmetic adverse events (AEs) following C&E.

In some cases, depressed scars on the nose or tissue contraction on the lips were reported.

cSCC is often successfully treated with surgical modalities; however, if surgical therapy is not feasible, low-risk tumors may be treated with nonsurgical modalities. Radiation therapy may be considered for low-risk tumors, because the rate of cure may be diminished.

Cryosurgery is an option for low risk cSCC if other therapies are contraindicated or impractical. Topical therapies, including imiquimod, 5-fluorouracil, and photodynamic therapy (PDT), are not evidence-based recommendations. Additionally, due to lack of data, no official recommendations have been made with respect to the use of laser therapies or electronic surface brachytherapy.

Primary radiation therapy can be used for patients for whom surgery is contraindicated, not feasible, or not preferred. Different types of radiotherapy have been used to treat cSCC, including external electron beam radiation, superficial radiation therapy, and isotope-based brachytherapy. Radiation therapy has been shown to result in good tumor control and cosmesis in select patients with cSCC.

However, disease-specific survival at 4 years was shown to be only 60% in patients with cSCC, compared with 100% in patients with BCC following radiation therapy.

Following surgical treatment, patients with primary cSCC and perineural invasion or those at high risk for metastasis may be considered for adjuvant radiation therapy.

Because only case reports or small case series have been reported regarding the treatment of cSCC with topical imiquimod, it is not currently recommended for cSCC.

5-fluorouracil has been used both alone and in combination as a treatment for cSCC, but it has been associated with erythema, erosions, and crust that can last for &ge;1 month, which can lead to decreased treatment adherence and diminished effectiveness.

Imiquimod has also been shown to lead to erythema, edema, erosions, ulceration, and crust. This can vary among patients, leading to difficulties with dosing decisions. When imiquimod is used on larger surface areas, systemic symptoms may be reported, such as headache, fatigue, myalgia, and influenza-like symptoms.

The use of PDT has demonstrated benefits in high-risk patients with invasive cSCC, including solid organ transplant recipients, when used in combination with curettage or surgery; however, the specific contribution of PDT to the observed outcomes is unclear.

Patients with cSCC have been reported to have a risk for metastasis of 3.7%.

Recommendations for therapy are based on the extent of disease; the primary choices consist of surgical resection, possible lymph node dissection, and the use of adjuvant radiation therapy with or without concurrent systemic therapy.

Multidisciplinary decision-making is recommended for metastatic cSCC because of the rarity and complexity of disease. Palliative and supportive care should be offered to patients with advanced disease, to improve symptom management and quality of life.

Chemotherapy has demonstrated some activity in patients with distant metastatic cSCC. In a study of patients treated with cisplatin-based chemotherapy, 28% achieved complete remission and 40% achieved partial remission following the use of chemotherapy alone. Moreover, all patients who received surgery following cisplatin-based chemotherapy (n = 5) achieved complete remission, with only 1 patient relapsing. Additionally, 7 of 8 patients who received radiation therapy following cisplatin-based chemotherapy achieved complete remission, with no relapses reported.

A study investigating the combined effects of interferon alfa, retinoic acid, and cisplatin demonstrated response rates of 67% in patients with locally advanced disease and 17% in those with metastatic disease, yielding an overall response rate (ORR) of 34%.

EGFR inhibitors have also been investigated for the treatment of patients with advanced unresectable cSCC. In a study of 36 patients treated with cetuximab, the disease control rate was 69%; 2 patients achieved complete responses and 8 achieved partial responses.

The most frequently reported AE was a grade 1 to 2 acne-like rash in 87% of the per-protocol population.21 Grade 3 or 4 serious adverse events (SAEs) were reported in 61% of patients; only 10% of the events were related to cetuximab.

A total of 4 patients experienced an SAE and discontinued treatment, whereas other patients experiencing grade 3 or 4 SAEs continued cetuximab without a dose reduction.

Results from a phase II study of 16 patients treated with panitumumab demonstrated a best ORR of 31%, including 3 partial responses, 2 complete responses, and 6 patients achieving stable disease.

Of the patients who experienced complete responses, 1 relapsed with distant metastatic disease at 16 months after the last panitumumab dose; the other patient received 7 panitumumab infusions and exhibited no evidence of disease at 24 months following the last dose.

No hypersensitivity reactions related to panitumumab were reported at the first infusion.

Immunocompromised patients, particularly those who are solid organ transplant recipients, have a risk for cSCC, which is increased by 198-fold among heart and lung recipients, 121-fold among kidney recipients, and 32-fold among liver recipients.

These figures suggest that immune surveillance may be critical for the prevention of cSCC in this population. A case report of patients with BCC and cSCC who were treated with an antibody directed against the PD-1 immune checkpoint receptor suggests that these cancers are sensitive to PD-1 blockade.

Cemiplimab, a human monoclonal antibody that targets PD-1, has been investigated as a treatment for patients with metastatic or locally advanced cSCC.

In expansion cohorts of a phase I study investigating cemiplimab in patients with metastatic or locally advanced cSCC, 50% of patients achieved a response.

Phase II results in the metastatic-disease cohort reported a response in 47% of patients, with the duration of response exceeding 6 months in 57% of patients, and 82% continuing to exhibit a response with cemiplimab treatment at data cutoff.

Frequently reported AEs in the phase II portion of the study included fatigue, diarrhea, nausea, constipation, and rash. Treatment discontinuation due to AEs was reported in 7% of patients.

Cemiplimab was recently approved by the FDA for patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or radiation.

This approval was based on results from the open-label R2810-ONC-1423 study, which included patients with various advanced solid tumors, and the open-label R2810-ONC-1540 study, which included patients with metastatic or locally advanced cSCC regardless of prior treatment.

Of the 108 patients with advanced disease (metastatic, n = 75; locally advanced, n = 33), the ORR was 47%.

Patients with metastatic or locally advanced disease had ORRs of 47% and 49%, respectively.

Overall, 61% of responses were durable for &ge;6 months.

The most common AEs reported in the 534 patients from both trials were rash, fatigue, and diarrhea.

Immune-mediated adverse reactions including pneumonitis, colitis, hepatitis, nephritis, adrenal insufficiency, diabetes mellitus, hypo- and hyperthyroidism, and infusion reactions were also reported.

Future Therapies Several additional therapeutic options are under investigation in clinical trials, including topical creams, chemotherapy, targeted therapy, and immunotherapy (TABLE).

A first-in-human, proof-of-concept, phase I/II study has been designed to assess the safety, tolerability, and initial efficacy of CLL442 cutaneous cream compared with placebo following &le;84 days of twice-daily application on a single cSCC lesion.

The combination of capecitabine or 5-fluorouracil with pegylated interferon alpha-2b is under investigation in a phase II study of patients with cSCC.

The primary outcome is the ORR per participant after 9 weeks, with secondary outcomes of 1-year progression-free survival, 1-year overall survival, and the occurrence of treatment-related SAEs.

A phase I study was designed to determine the maximum tolerated dose of lenvatinib when combined with cetuximab in patients with recurrent or metastatic head and neck cSCC.

The safety and efficacy of pembrolizumab is under investigation in a phase II study of adult participants with recurrent or metastatic cSCC who are not eligible for surgery, radiation, and systemic therapies.

Because of its success in human papillomavirus (HPV) associated head and neck SCC, HPV has been suggested as a promising target for the treatment of cSCC.

MicroRNAs (miRNAs) have been shown to suppress the expression of target genes and have been associated with both the onset and progression of various cancers, implicating their potential as targets in cancer therapies.30 miRNA-1, miRNA-34a, and miRNA-124/214 have been shown to be deregulated in cSCC.

These miRNAs target important molecules of cell proliferation, which are often upregulated in cancer cells; therefore, promoting the overexpression of these miRNAs may be an option for therapeutic development.

Several recommended treatment strategies are available that are effective for most patients with cSCC. However, there are fewer recommended options for patients with recurrent or metastatic disease. Cemiplimab recently received FDA approval as the first systemic treatment for patients with recurrent or metastatic disease who are not candidates for curative surgery or radiation therapy. The need remains for additional therapies in this high-risk group to improve quality of life and survival and to facilitate the reduction in the large financial burden associated with this common cancer.

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Although it is the second most common form of skin cancer in the United States, cutaneous squamous cell carcinoma can often be effectively treated with a variety of surgical modalities, such as standard excision, Mohs micrographic surgery, curettage and electrodessication, and cryosurgery.

Cutaneous Squamous Cell Carcinoma

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