Referral Barriers Persist in Advanced Cutaneous Squamous Cell Carcinoma Care

Nina Ran, MD, MPH, MSTR, recently led a Dermatology Times Evolving Paradigms event in Boston, guiding a discussion among dermatologists and medical oncologists on multidisciplinary management of advanced cutaneous squamous cell carcinoma. The group reviewed a single patient case alongside data from 3 pivotal immunotherapy trials, then discussed real-world agent selection, referral coordination, and surveillance strategy.

Weighing Mechanism of Action Among the Approved Agents

Ran, a dermatologist and Mohs surgeon at Brigham and Women’s Hospital and an instructor in dermatology at Harvard Medical School, opened by asking how differences in mechanism of action influence agent selection; cemiplimab (Libtayo; Regeneron) and pembrolizumab (Keytruda; Merck) bind PD-1, while cosibelimab (Unloxcyt; Sun Pharma) binds PD-L1 and retains Fc-mediated activity. One attendee called the antibody-dependent cellular cytotoxicity data for cosibelimab intriguing but preclinical, noting it has only been observed in Jurkat cells and has not been validated clinically in squamous cell carcinoma. Another attendee said cosibelimab shows a surprisingly low rate of immunotherapy toxicity in trial data, though the group agreed the finding needs validation in a larger population before it changes standard selection.

Discussion soon turned to raw efficacy numbers. Attendees compared response rates across CK-301-101 (NCT03212404), EMPOWER-CSCC-1 (NCT02760498), and KEYNOTE-629 (NCT03284424), noting complete response rates are consistently lower in metastatic disease than in locally advanced disease. Several speculated the gap reflects impaired host immune function once disease has spread, though one attendee also pointed to RECIST-specific factors, like residual scarring or sclerotic bone lesions, blocking a formal complete-response call even when a patient looks clinically disease-free.

Referral Coordination Remains Inconsistent Across Practice Settings

The group's single patient case, a 72-year-old man with a poorly differentiated scalp tumor who progressed with neuropathic pain and pulmonary nodules 8 months after Mohs surgery, parotidectomy and adjuvant radiation, prompted a broader conversation about how patients move between dermatology and oncology. Attendees at large academic centers described dedicated triage teams and shared electronic records streamlining referrals. Ran noted staging and surveillance imaging for CSCC are inconsistent practices among community dermatologists.

"I would say among dermatologists, staging is probably low, and surveillance imaging is even lower. It's much lower. It's just not common practice," Ran said.

One attendee in private practice described the opposite experience, contrasting CSCC referrals with the streamlined process for a melanoma diagnosis.

"It's like a black hole that you don't know who to call," the attendee said.

Even shared electronic record systems did not fully resolve the friction, as attendees described permission barriers between institutions on the same platform.

Real-World Selection Is Shifting Toward Cosibelimab

Several attendees described choosing cemiplimab historically because supporting neoadjuvant data emerged earliest, then more recently adding cosibelimab for its lower rate of immune-related toxicity, hypothesized to relate to preserved PD-L2 signaling protecting lung tissue. One attendee cautioned the hypothesis remains unproven and pointed to a design difference: the cosibelimab trial had no US investigators, as a possible confounder in adverse event reporting.

"I think efficaciously, they're equal," the attendee said, adding a confirmed safety edge for cosibelimab would be reason enough to try it in frail patients.

Front-Line Immunotherapy Is Reshaping Surgical Timing

One attendee described a shift away from routine surgery after immunotherapy response, describing a cohort of resectable patients treated with upfront immunotherapy rather than neoadjuvant intent, with imaging and exam findings driving subsequent decisions instead of a fixed surgical endpoint.

"We are just slowly letting the biology declare itself," the attendee said, describing the approach as "first" therapy rather than neoadjuvant therapy, since many patients never proceed to surgery.

A Mohs surgeon on the panel said clinically disease-free patients rarely need surgery afterward, and expressed reluctance to operate on frail, older patients whose imaging and exam findings look clean.

Adjuvant Immunotherapy Divides the Group

Attendees disputed how to interpret 2 recent adjuvant immunotherapy trials with differing statistical outcomes, one meeting significance for disease-free survival and one falling short despite a similar point estimate favoring treatment. One attendee argued the difference reflects trial design and enrollment challenges rather than a true biological difference between agents. Another said routinely treating high-risk patients for a full year of adjuvant therapy overtreats many who were already cured by surgery, given recurrence rates well under 50%.

Attendees also raised the toll low-grade immunotherapy toxicity takes on older, frail patients juggling multiple specialist visits.

"Time toxicity, financial toxicity are the words I use to patients to help them think," one attendee said.

Ran closed the evening by thanking the group for a wide-ranging exchange touching on nearly every stage of the CSCC treatment pathway, from initial referral through long-term surveillance.

This event recap has been produced independently by Dermatology Times and supported through an educational grant by Sun Pharmaceuticals.

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