Tumor depth confers the highest risk of local recurrence and metastasis of cutaneous squamous cell carcinoma (cSCC)  and tumor diameter exceeding 20 mm is associated with the highest risk for disease-specific death, a new study suggests.

The findings are published online in JAMA Dermatology.

cSCC is the second most common skin cancer, with an estimated annual incidence of 700 000 cases in the United States. Most cases portend an excellent prognosis after surgical removal, however, 3.7% to 5.2% of patients have nodal metastasis, and 1.5% to 2.1% die of cSCC, and the study authors point out.

In a review of 36 studies comprising 17, 248 patients with 23 421 cSCCs, significant risk factors for recurrence were Breslow thickness exceeding 2 mm (risk ratio [RR], 9.64; 95% CI, 1.30-71.52), invasion beyond subcutaneous fat (RR, 7.61; 95% CI, 4.17-13.88), Breslow thickness exceeding 6 mm (RR, 7.13; 95% CI, 3.04-16.72), perineural invasion (RR, 4.30; 95% CI, 2.80-6.60), diameter exceeding 20 mm (RR, 3.22; 95% CI, 1.91-5.45), location on the temple (RR, 3.20; 95% CI, 1.12-9.15), and poor differentiation (RR, 2.66; 95% CI, 1.72-4.14). Moreover, significant risk factors for metastasis were invasion beyond subcutaneous fat (RR, 11.21; 95% CI, 3.59-34.97), Breslow thickness exceeding 2 mm (RR, 10.76; 95% CI, 2.55-45.31), Breslow thickness exceeding 6 mm (RR, 6.93; 95% CI, 4.02-11.94), diameter exceeding 20 mm (RR, 6.15; 95% CI, 3.56-10.65), poor differentiation (RR, 4.98; 95% CI, 3.30-7.49), perineural invasion (RR, 2.95; 95% CI, 2.31-3.75), immunosuppression (RR, 1.59; 95% CI, 1.07-2.37), and location on the temple (RR, 2.82; 95% CI, 1.72-4.63), ear (RR, 2.33; 95% CI, 1.67-3.23), or lip (RR, 2.28; 95% CI, 1.54-3.37), the study found.

Significant risk factors for disease-specific death were diameter exceeding 20 mm (RR, 19.10; 95% CI, 5.80-62.95), poor differentiation (RR, 5.65; 95% CI, 1.76-18.20), location on the ear (RR, 4.67; 95% CI, 1.28-17.12) or lip (RR, 4.55; 95% CI, 1.41-14.69), invasion beyond subcutaneous fat (RR, 4.49; 95% CI, 2.05-9.82), and perineural invasion (RR, 4.06; 95% CI, 3.10-5.32).

Study limitations include the possibility that pertinent studies were missed due to inherent limitations in database literature searches. In addition, most data is derived from single-center experiences and retrospective analyses, with heterogeneous data reporting and study design and some included studies had variable and at times limited follow-up.

“In the short term, these results may help guide physicians in their risk assessment of patients, particularly those with only 1 identified risk factor, while keeping in mind the inherent limitations of the data,” conclude researchers who were led by Christian L. Baum, MD, a dermatologist at the Mayo Clinic in Rochester, Min. “In the long term, these results may be used to refine the evolving work on staging systems for cSCC, while providing a renewed call to action for data collection. Not only are unambiguous definitions for each risk factor needed, but also comprehensive, uniform reporting of risk factors and outcomes is necessary to provide optimal care for the increasing number of patients with cSCC in the United States and globally."