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.
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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.
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.
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).
In adjuvant bladder cancer trials, ctDNA status is both prognostic and predictive. Patients with positive ctDNA after surgery are at high risk of relapse but benefit from immune checkpoint inhibitors. Conversely, ctDNA-negative patients have a lower risk and derive no benefit, making ctDNA a critical tool to avoid unnecessary, toxic therapy.
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.
When a sentinel lymph node biopsy is skipped, radiation oncologists lack crucial staging information. This can make them hesitant to recommend less-invasive partial breast radiation, even if a patient otherwise qualifies. They may instead recommend whole breast radiation to treat any potential, unconfirmed microscopic disease in the axilla.
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.
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.
Based on 'Choosing Wisely' guidelines, surgeons can skip sentinel lymph node biopsy in women over 70 with small, hormone receptor-positive, HER2-negative breast cancer. This de-escalates treatment by avoiding an unnecessary procedure with a very low likelihood of finding cancer spread, minimizing potential complications for patients.