Chapter 9: Cutaneous Squamous Cell Carcinoma

BURDEN

An argument could be made that cutaneous squamous cell carcinoma (cSCC) is a neglected cancer globally. cSCC imposes a significant disease burden on health care systems, with an estimated 250,000 cases diagnosed annually in the United States. Yet, its true incidence is difficult to decipher as it is not generally recorded in tumor registries. Some statistics are frankly alarming.¹

The burden has shown a dramatic increase over recent decades. Metastases and deaths from cSCC are still regarded by many as black swan events. Black swan events represent extreme outliers (outside the sphere of normal to such a degree that nothing in the past suggests its possibility), result in an acute impact, and are only explainable following the event. But cSCC disease burden is increasing both in terms of incidence and mortality to such an extent that deaths from cSCC have been estimated to exceed those caused by melanoma in some populations. The increase has been attributed largely to cumulative sun exposure, the advent of new immunosuppression therapies, and organ transplantation.

Like the underappreciation of disease burden, research interest in and funding for cSCC lags behind that of other malignancies. The lack of available tumor material is a significant barrier to research. A typical patient with metastatic cSCC has innumerable possible primary tumors and deciphering which one was responsible for the metastasis can be impossible. This is not frequently discussed and, disappointingly, many studies looking into risk use pathology reports without slide review or proper consideration of which skin tumor is responsible for the metastatic disease.²

Margin control surgery (MCS) is an attractive therapeutic option. cSCC has a propensity to occur on cosmetically and functionally sensitive sun-damaged skin; it usually grows in a predictable cohesive pattern; usually has a recognizable histopathology; and complete excision is usually associated with an excellent prognosis.

EVIDENCE

To date, no comprehensive randomized control trials or prospective cohort studies have been performed which compare MCS with other treatment modalities. In a systematic review of the literature since 1940, Rowe et al. reported a five-year local recurrence rate of 3.1% (n = 2065) for primary cSCC treated with MCS and a rate of 8.1% for WLE. When high-risk factors were considered, MCS has shown even more favorable outcomes: a local recurrence rate of 25.2% versus 41.7% for tumors 2 cm or larger, 32.6% versus 53.6% for poorly differentiated cSCC, and 0% versus 47% for neurotropic cSCC. For recurrent cSCC, the meta-analysis by Rowe et al. revealed a five-year recurrence rate after MCS of 10.0% (n = 151) compared with 23.3% (n = 34) following WLE.^3-6

CLINICAL PRESENTATION

cSCC has quite a wide range of clinical presentations. Thin lesions are often erythematous scaly papules or plaques. Thicker tumors typically present as an indurated erythematous plaque, nodule, or ulcer. Invasive ...