Immunotherapy for early-stage cutaneous squamous cell carcinoma

Area of Science:

• Oncology
• Dermatology
• Immunotherapy

Background:

• Cutaneous squamous cell carcinoma (CSCC) is a common cancer with increasing incidence, especially in the elderly and immunosuppressed.
• While surgery cures early CSCC, high-risk or complex cases require advanced treatments.
• Immune checkpoint inhibitors (ICIs) are revolutionizing advanced CSCC care and are being explored in perioperative settings.

Purpose of the Study:

• To review the current evidence on neoadjuvant and adjuvant immunotherapy for resectable CSCC.
• To analyze the efficacy and limitations of existing treatment strategies.
• To identify future directions for precision medicine in early CSCC management.

Main Methods:

• Critical review of clinical trial data for neoadjuvant and adjuvant ICIs in resectable CSCC.
• Analysis of response rates, survival outcomes, and limitations of current staging systems.
• Evaluation of trial design, inclusion criteria, and generalizability of findings.

Main Results:

• Neoadjuvant ICIs (cemiplimab, pembrolizumab, nivolumab±ipilimumab) demonstrate high major and complete pathologic response rates (>50%), enabling potential de-escalation of surgery or radiotherapy.
• Adjuvant anti-PD-1 trials (KEYNOTE-630, C-POST) yielded conflicting results, with one negative and another showing improved disease-free survival but not overall survival.
• Current staging systems inadequately capture disease biology, immunosuppression, and surgical complexity, limiting treatment personalization.

Conclusions:

• Neoadjuvant immunotherapy offers significant benefits for resectable CSCC, facilitating organ preservation.
• Adjuvant immunotherapy's role remains uncertain due to trial discrepancies and limitations in risk stratification.
• Future CSCC management requires response-adapted, biomarker-driven strategies within a precision medicine framework, broadening inclusion criteria for diverse patient populations.