Neoadjuvant anti–PD-1 immunotherapy drives 54% pCR and improves 2-year EFS in resectable stage III–IV cSCC

In a single-institution retrospective series of resectable stage III/IV cutaneous squamous cell carcinoma treated 2010–2024 (n=300), neoadjuvant (NEO) anti–PD-1 immunotherapy (median 3 cycles) followed by surgery was compared with upfront surgery (US)±adjuvant therapy (NEO n=106; US n=194). In the NEO cohort, 82% proceeded to surgery and achieved pCR 54% (47/87), near-pCR 11% (10/87), and pathologic partial response 9% (8/87); 2-year EFS was 90% with NEO vs 79% with US (p=0.013), and any pathologic response correlated with markedly higher 2-year EFS vs non-response (98% vs 61%, p<0.001). Post-op RT was far less frequent with NEO vs US (26% vs 72%), but baseline imbalances (US had more stage III and more immunocompromised patients) complicate direct comparisons—still, the pCR rate aligns with prior prospective neoadjuvant PD-1 experiences in resectable cSCC (≈50% pCR), and the ongoing Phase 3 trial (NCT06568172) is the right next step.