Investors often compare new drugs to the most effective treatments on efficacy alone. In practice, dermatologists will almost always choose a safer drug with lower efficacy first, creating a huge market for treatments that aren't "best-in-class" but have a superior safety profile.

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.

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.

Among solid organ transplant patients, who are already at high risk for skin cancer, heart transplant recipients are at the greatest risk. This is specifically due to the type and duration of immunosuppressive drugs required to prevent organ rejection, highlighting a critical sub-population for dermatologic surveillance.

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.

Nonmelanoma skin cancers' sensitivity to checkpoint inhibitors is due to high tumor mutational burden (TMB) caused by chronic UV light damage. This high TMB creates numerous neoantigens, which the immune system can effectively target once immunotherapy reverses immune suppression.

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.

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.

The high efficacy of checkpoint inhibitors in cutaneous squamous cell carcinoma is enabling a "de-escalation" strategy. Upfront systemic therapy can be so effective that it eliminates the need for subsequent morbid local treatments like extensive surgery or radiation, a major benefit for elderly patients.