Many elderly patients with advanced nonmelanoma skin cancer neglect their tumors due to psychosocial or financial reasons. Integrating social workers into the multidisciplinary team is crucial for addressing these root causes and ensuring comprehensive care, not just medical treatment.
An emerging area of research is intralesional immunotherapy, where anti-PD-1 drugs are injected directly into early-stage cutaneous squamous cell carcinomas. This approach may provide effective local control for tumors in anatomically challenging locations while minimizing systemic toxicity.
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.
Though typically contraindicated, checkpoint inhibitors can be used for transplant recipients with advanced skin cancer. This requires shared decision-making, collaboration with the transplant team, and a specific protocol involving high-dose pulse steroids to mitigate the high risk of allograft rejection.
Clinicians must counsel patients that some drug toxicities are irreversible or create lifelong conditions. Alopecia from hedgehog inhibitors can be permanent, while immunotherapy-induced adrenal insufficiency or Type 1 diabetes require daily management, a significant quality-of-life burden for older patients.
Unlike in lung cancer, PD-L1 expression levels do not guide treatment for nonmelanoma skin cancers. Patients with low or even negative PD-L1 levels still show significant response to anti-PD-1 therapy, making the test an unhelpful discriminator for treatment decisions.
Hedgehog inhibitors for basal cell carcinoma cause significant side effects like dysgeusia and muscle cramps. To improve tolerability and long-term adherence, clinicians use practical strategies like scheduled treatment interruptions (e.g., weeks on, weeks off) rather than continuous daily dosing.
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.