Saeed Salman, Chief Physician at Rambam Health Care Campus, shared a post on X:
“Unpopular opinion: upfront surgery as standard of care for locally advanced cutaneous SCC of the head and neck is becoming outdated.
Here’s why the data – including our own real-world experience from Israel – demands we rethink the paradigm.
cSCC has among the highest tumor mutational burden of any solid tumor – driven by UV-induced DNA damage.
This makes it arguably THE most immunotherapy-responsive disease outside Merkel cell carcinoma. We’ve been slow to act on what the biology has been telling us for years.
The NEJM phase 2 neoadjuvant cemiplimab trial (Gross et al.) showed:
- pCR in 51% of patients
- ORR on imaging 68%
- 0/40 pCR patients had recurrence at follow-up
- 12-month DFS 92% Let that sink in. Half of patients had zero viable tumor cells at surgery. And none recurred
Here’s the part that doesn’t get enough attention:
Radiologic response UNDERESTIMATES pathologic response.
Only 6% had radiologic CR – but 51% had pCR on pathology.
We are using imaging to make surgery decisions on patients who may already have no viable disease.
Our real-world data from Israel confirm extremely high response rates to first-line IOI in HandN cSCC. The RAMPART trial (MSK-led, phase II) is now prospectively testing response-adapted definitive RT + cemiplimab – no surgery – in locally advanced unresectable cSCC.
At our center – a high-volume HandN oncology program – fewer than 5% of locally advanced cSCC patients proceeded to surgery over the past 4 years. Almost no recurrences. This isn’t anecdote. This is what happens when you treat the biology.
NCCN now allows neoadjuvant cemiplimab before surgery in very-high-risk resectable disease, and adjuvant cemiplimab post-RT. But there is still NO pathway for: IO-CR-omit surgery. This is the gap. And it’s costing patients function, cosmesis, and quality of life.
We’ve been here before. In the 1990s, the VA larynx trial and RTOG 91-11 dismantled total laryngectomy as the default for advanced laryngeal SCC. It took randomized data + institutional courage to change practice. Head and neck cSCC is at the same inflection point – right now.
What we need: A prospective surgery-omission trial in cSCC patients with CR/near-CR to neoadjuvant immunotherapy Validated non-surgical biomarkers for pCR High-volume centers, treating well publish it The data are there. The trial design is obvious. Who’s running it?
Bottom line: For locally advanced HandN cSCC in 2025, the question is no longer ‘immunotherapy before surgery?‘
It’s ‘why are we still doing surgery in complete responders?’ Happy to be challenged on this. The patients deserve the debate.”
Other articles about Skin Cancer on OncoDaily.