The success of immunotherapy in neoadjuvant and adjuvant settings has rendered the traditional, sequential referral model (dermatologist to surgeon to oncologist) obsolete. Optimal care now demands an integrated, team-based discussion among all specialists *before* the first treatment decision is made to determine the best sequence and timing.

Sentinel lymph node biopsy was historically inconsistent in CSCC because a positive finding had no approved systemic treatment path. With adjuvant cemiplimab's approval, identifying microscopic nodal disease now directly impacts treatment eligibility, potentially making the procedure a new standard of care for certain high-risk patients.

Genetic tests like DecisionDX for squamous cell carcinoma are evolving from simply predicting recurrence risk to actively informing treatment choices. Ongoing studies are exploring whether these tests can determine a patient's potential benefit from adjuvant radiation therapy, representing a critical step toward personalized medicine.

Immuno-oncology is not a one-time fix because cancer cells are described as "smart" adversaries that quickly adapt and develop resistance. The future of treatment lies in staying a step ahead, constantly switching therapeutic mechanisms to outmaneuver the cancer's ability to learn.

With 72% response rates to neoadjuvant immunotherapy, surgeons are shifting from immediate, aggressive surgery to a "wait-and-see" approach. Shrinking the tumor first can turn a morbid, disfiguring operation into a much simpler procedure, fundamentally changing the initial surgical evaluation for cutaneous squamous cell carcinoma (CSCC).

The future of medicine isn't about finding a single 'best' modality like CAR-T or gene therapy. Instead, it's about strategic convergence, choosing the right tool—be it a bispecific, ADC, or another biologic—based on the patient's specific disease stage and urgency of treatment.

The next frontier in CSCC isn't just about new drugs, but about optimizing existing ones. A key research area is determining the minimum number of immunotherapy doses required for an optimal response—potentially just one or two—to limit toxicity, reduce treatment burden, and personalize care for high-risk patients.

Standard cancer surgery often removes lymph nodes—the factories producing immune cells. Administering immunotherapy *before* this destructive process is critical. It arms the immune system while it is still intact and capable of mounting a powerful, targeted response against the tumor.

Rather than moving through distinct lines of therapy, a future strategy could involve an "ADC switch." When a patient progresses on an ADC-IO combination, the IO backbone would remain while the ADC is swapped for one with a different, non-cross-resistant mechanism, adapting the treatment in real-time.