WEDNESDAY, March 19, 2025 -- For patients with cutaneous squamous cell carcinoma (cSCC), the number of risk factors (RFs) is associated with recurrence, metastasis, and disease-related death, according to a study published online March 19 in JAMA Dermatology.

Nina A. Ran, M.D., from Brigham and Women's Hospital in Boston, and colleagues examined how RF number is associated with the risk for recurrence, metastasis, and disease-related death in a retrospective multination cohort study of cSCCs diagnosed between Oct. 1, 1991, and July 19, 2023. A total of 16,844 cSCCs with confirmed negative margins were included.

Overall, 75.1, 17.2, 6.0, 1.3, and 0.3 percent of the tumors had zero, one, two, three, or four RFs, respectively (diameter of 2 cm or larger; poorly differentiated histology; tumor extension beyond subcutaneous fat; and large caliber nerve invasion). The researchers found that the risk for local recurrence increased as the number of RFs increased from zero to one, two, three, and four (1.7, 5.0, 8.8, 16.0, and 33.0 percent, respectively). Corresponding increases were also seen for nodal metastasis (0.6, 3.6, 11.0, 20.0, and 28.0 percent), distant metastasis (0.2, 1.1, 2.3, 7.9, and 8.4 percent), and disease-specific death (0.3, 1.9, 5.4, 11.0, and 25 percent). Higher cumulative incidences of local recurrence, nodal metastasis, distant metastasis, and disease-specific death were seen for cSCCs with three versus two RFs (1.6-, 1.9-, 4.3-, and 1.9-fold higher, respectively).

"Considering the number of RFs, not just tumor stage, may aid in clinical decision-making," the authors write. "Future studies may consider refinements of staging systems based on the number of RFs."

Several authors disclosed ties to the biopharmaceutical industry.