While nomograms are useful for quantifying risk in primary CSCC tumors, their predictive power diminishes significantly once a patient has a regional recurrence. Clinicians should use them cautiously in the recurrent setting, as their original design and validation are based on primary tumors.
Contrary to the common assumption that metastatic disease is the primary cause of cancer-related death, a large international study on CSCC found that two-thirds of patients died from local-regional uncontrolled progression. This highlights the critical importance of effective local control strategies.
In a neoadjuvant cemiplimab trial, only 6% of patients had a complete response based on radiographic imaging (RECIST criteria), yet 50% achieved a pathologic complete response. This major discrepancy shows clinicians should not rely solely on scans to assess treatment benefit before surgery.
Patients receiving systemic immunotherapy for advanced skin cancer are still at high risk for developing new, low-risk primary skin cancers. Medical oncologists should not act as default dermatologists; ongoing co-management is crucial to identify and treat these new lesions while the patient is on systemic therapy.
In a pivotal neoadjuvant trial of cemiplimab for CSCC, none of the 40 patients who achieved a pathologic complete response (path CR) had relapsed at long-term follow-up. This suggests that path CR can be used as a powerful early indicator of long-term disease control and potential cure.
Clinical experience suggests that CSCC recurring within or at the edge of a prior radiation field tends to exhibit more aggressive biological behavior. This context is a critical factor when assessing risk and deciding on subsequent treatment, such as adjuvant systemic therapy, even if other features seem borderline.
Experts argue that radiation therapy is often wrongly perceived as a salvage or adjuvant option. For many patients with early-stage basal or squamous cell carcinomas, it offers local control rates over 95%, comparable to surgery, and should be presented as a primary alternative, especially when cosmetic outcomes are a priority.
While neoadjuvant hedgehog inhibitors can successfully downstage locally advanced basal cell carcinoma (BCC) before surgery, the three-year recurrence rate is a surprisingly high 36%. This indicates that this strategy reduces surgical complexity but does not eliminate the high underlying risk, often necessitating further treatment.
Instead of basing adjuvant radiation decisions on a patient's initial, pre-treatment tumor stage, clinicians should use the post-neoadjuvant pathological stage (ypTNM). Patients with a major pathologic response (e.g., downstaging from T3 to T1) may be able to safely avoid additional adjuvant radiation therapy.
Clinicians should not treat all immunosuppression as a monolithic high-risk factor for skin cancer. Recent data show that lymphoproliferative disorders like chronic lymphocytic leukemia (CLL) pose a much greater risk for aggressive CSCC than many modern solid organ transplant medication regimens.
Experts advise against using gene expression profiling to escalate care for CSCC (e.g., deciding to add systemic therapy). Its primary utility is in de-escalation: a low-risk profile can provide an additional data point to support a decision for observation in a borderline high-risk case, helping to avoid overtreatment.
Despite both being keratinocyte-derived skin cancers, basal cell carcinoma (BCC) responds much less robustly to immunotherapy than cutaneous squamous cell carcinoma (CSCC). The pathologic complete response rate to perioperative PD-1 inhibition in BCC is only 23%, less than half the 51% seen in CSCC, highlighting their distinct immunobiology.