Immunosuppressed patients are at increased risk of local recurrence, metastasis, and disease specific death from cutaneous squamous cell carcinoma.

It is well established that immunosuppressed patients are at increased risk for poor outcomes (PO) from cutaneous squamous cell carcinoma (cSCC), including local recurrence (LR), nodal metastasis (NM), distant metastasis (DM), and disease-specific death (DSD). Defining PO risk is challenging but may be beneficial in guiding management. We aimed to define PO risk factors and evaluated their importance in immunosuppressed versus immunocompetent patients. We conducted a 4-year single-center retrospective review of patients with cSCC. Patient and tumor characteristics were evaluated in those that experienced PO. Immunosuppressed patients were ~ 11-fold more likely than immunocompetent patients to develop PO (10/85 vs. 15/1332, p < 0.0001). Among those with PO, immunosuppressed patients had diminished relapse free (p = 0.026) and progression free (p < 0.001) survival compared to immunocompetent. Immunosuppression was significantly associated with LR (p < 0.00001). Immunosuppressed patients were also more likely to develop NM, DM and experience DSD (p = 0.027). Mohs Appropriate Use Criteria was associated with NM, DM and DSD (p = 0.029), with area H tumors more likely to result in metastasis and death. In conclusion, immunosuppressed patients are more likely to develop LR, metastasis, and DSD from cSCC compared to immunocompetent patients. Immunosuppressed status was an independent risk factor for PO in this cohort and further considered for its inclusion in prognostication schema is warranted.