Could Immunotherapy Change How We Manage the cN0 Neck?
Journal: Int J Oral Maxillofac Surg (2025) Study Type: Review Article Authors: Bu LL, Xu ZY, Kuo ZY, Wei LY, Liu B, Jia J Institution: Wuhan University, China DOI: 10.1016/j.ijom.2025.04.1143
Why This Matters
Every head and neck surgeon faces this dilemma daily: you've got a patient with a T1 or T2 oral cavity cancer and a clinically negative neck. Do you perform an elective neck dissection — knowing that 70% of these patients don't actually have occult metastases? Or do you watch and wait, risking delayed treatment if disease is lurking?
This review from Wuhan University proposes a provocative idea: what if neoadjuvant immunotherapy could eliminate occult metastases, allowing us to spare patients from neck dissection altogether?
The Current Landscape
The case for END is strong:
The D'Cruz trial (2015) showed 12.5% improvement in overall survival with END vs. observation
Multiple meta-analyses confirm END reduces recurrence and improves survival
It's the current standard of care for cT1-T2N0 OSCC
But END comes at a cost:
Up to 70% of patients receive unnecessary surgery
Permanent shoulder dysfunction occurs in 22-39% of cases
Significant impact on quality of life
Sentinel node biopsy (SLNB) offers a middle ground with 90-98% negative predictive values, but remains technically demanding and underutilized.
The Immunotherapy Angle
Here's where it gets interesting. The authors highlight emerging evidence that:
Lymph nodes are critical for immunotherapy response — They contain progenitor T cells (TCF1+) that drive the anti-tumor immune response to checkpoint inhibitors
Intact lymph nodes respond better — Metastatic lymph nodes develop an immunosuppressive microenvironment similar to the primary tumor
Removing lymph nodes may impair immunotherapy efficacy — If we dissect healthy, uninvolved nodes, we may be removing the very tissue needed to mount an immune response
The Proposal
The authors suggest a paradigm shift for cT1-T2N0 OSCC:
Neoadjuvant immunotherapy + Watch-and-wait instead of Elective neck dissection
The rationale:
Early-stage patients have healthier lymph nodes → better immune response potential
OSCC has high mutational burden → more neoantigens for T cell activation
Oral cavity tumors are easily monitored clinically → can track response without excessive imaging
If immunotherapy can eliminate occult micrometastases, END becomes unnecessary
What's Needed to Make This Work
The authors identify three key areas for development:
1. Better lymph node diagnostics
Current imaging misses microscopic disease
Novel approaches: nanoparticle-based imaging, photoacoustic imaging, EGFR-targeted fluorescent probes
2. Risk stratification systems
Depth of invasion helps but isn't definitive
Tumor budding scores and liquid biomarkers show promise
AI-based prediction models under development
3. Targeted drug delivery to lymph nodes
Nanoparticles, extracellular vesicles, cancer vaccines
Could enhance immunotherapy response while reducing systemic toxicity
Clinical Implications
For surgeons considering this approach:
This is still theoretical — no randomized evidence yet supports skipping END after neoadjuvant immunotherapy
One trial (NCT06130332) is actively comparing neoadjuvant immunochemotherapy + watch-and-wait vs. selective neck dissection, with 2-year DFS as the primary endpoint (completion: August 2027)
For tumor board discussions:
Worth considering neoadjuvant immunotherapy for locally advanced OSCC based on current data
For early-stage cN0 disease, END remains standard — but watch this space
For patient counseling:
The future may offer less invasive approaches
Current patients should still receive standard-of-care management
Limitations
This is a narrative review, not a systematic review or meta-analysis
The "neoadjuvant immunotherapy to avoid END" concept is largely theoretical
Response rates for lymph node metastases vary widely across studies
Long-term survival data for this approach in OSCC is lacking
The Bottom Line
This review makes a compelling biological argument: if lymph nodes are essential for immunotherapy response, maybe we shouldn't be removing them prophylactically. The concept of using neoadjuvant immunotherapy to control occult disease and spare patients from neck dissection is intellectually attractive — but we need randomized trial data before changing practice.
Watch for results from NCT06130332 in 2027. Until then, END remains the standard for cT1-T2N0 oral cavity cancer.
📄 Read the full paper: https://doi.org/10.1016/j.ijom.2025.04.1143