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.

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.

With highly effective neoadjuvant therapies now available, the surgeon's role in muscle-invasive bladder cancer is evolving. They are moving from being the primary decider and treater to being a key manager of a 'perioperative bundle,' where their first goal is often to get patients to medical oncology for systemic treatment.

Instead of a rigid, pre-defined treatment plan, clinicians are adopting a "response-determined" approach for cutaneous squamous cell carcinoma. A tumor initially deemed unresectable can become operable after just one or two doses of immunotherapy, requiring dynamic, ongoing collaboration between surgical and medical oncology teams to adjust the plan.

While oncologists focus on the low 4% rate of Interstitial Lung Disease (ILD) from neoadjuvant TDXD, surgeons worry this complication could prevent patients from reaching potentially curative surgery, drawing parallels to issues seen with neoadjuvant immunotherapy.

Dr. Radvanyi advocates for a paradigm shift: treating almost all cancers with neoadjuvant immunotherapy immediately after diagnosis. This "kickstarts" an immune response before standard treatments like surgery and chemotherapy, which are known to be immunosuppressive, can weaken the patient's natural defenses against the tumor.