When to Include Level IV in Elective Neck Dissections in cN0 Oral Cavity Squamous Cell Carcinoma (SCC)

The decision to extend a supraomohyoid neck dissection (levels I to III) to include level IV (extended supraomohyoid neck dissection):
- Hinges on whether pN+ disease is discovered in levels I to III, the number of positive nodes, and the pN classification
  - Below is a comprehensive review of the specific scenarios and supporting data
Scenario 1 – cN0 Neck → Intraoperative Discovery of pN+ Disease in Levels I to III:
- This is the most clinically relevant scenario
- When a patient undergoes END for a cN0 neck and positive nodes are found on frozen section or final pathology:
  - The risk of concurrent level IV to V disease rises substantially compared to the overall cN0 population
- The Haas et al. (2025) study directly addressed this question in 61 cN0 patients who were found to be pN+ in levels I to III [1]:
  - 9.8% (6/61) had metastases in levels IV to V:
    - Well above the 5% threshold generally used to justify elective dissection
    - > 1 positive node in levels I to III was the strongest predictor of level IV to V involvement (p = 0.027)
    - pN classification > pN2b significantly increased the prevalence of level IV to V metastases (p = 0.002)
    - Extracapsular spread (ECS) showed a trend toward increased IV to V involvement (p = 0.078), though not statistically significant in this cohort
    - This 9.8% rate stands in stark contrast to the 0.50% true skip metastasis rate in the overall cN0 population, underscoring that the discovery of pN+ disease in levels I to III fundamentally changes the risk calculus
Scenario 2 – cN+ Neck (Preoperatively Known Nodal Disease):
- For the clinically node-positive neck, both ASCO and NCCN guidelines explicitly recommend including level IV in the dissection [2][3]
- The ASCO guideline states:
  - An ipsilateral therapeutic selective neck dissection for a cN+ neck should include:
    - Nodal levels Ia, Ib, IIa, IIb, III, and IV with ≥ 18 lymph nodes (evidence-based, intermediate quality, moderate strength) [2]
  - The NCCN guidelines specify:
    - cN1 to cN2a–c disease warrants selective or comprehensive neck dissection [3]
- The American Head and Neck Society review provides the supporting data:
  - Occult level IV nodal metastatic disease is reported in 11.1% to 23.7% of cN+ oral tongue cancers, and 15% of all patients undergoing therapeutic neck dissection had level IV metastases [4]:
    - This rate is high enough that level IV dissection should be considered even in the absence of overt metastatic lymph node involvement at that level [4]
Scenario 3 – When to Add Level V:
- Level V dissection carries significant risk to the spinal accessory nerve and is not routinely recommended
- However, the data support its inclusion in specific circumstances [4]:
  - Clinical involvement of levels I to IV:
    - Was associated with occult metastases in level V in 27% of oral cavity SCCs in one study
  - Level V should be considered in patients with bulky, multilevel nodal disease
- The overall rate of level V metastasis:
  - In therapeutic neck dissections is only ~4%
Practical Decision Framework – When to Extend to Level IV:
- Prognostic Implications of Level IV Disease:
  - Importantly, the discovery of level IV or V disease is not merely an anatomic finding:
    - It carries significant prognostic weight
  - The NCCN guidelines list nodal disease in levels IV or V as an adverse pathologic feature:
    - Which triggers consideration of adjuvant systemic therapy / RT [3]
  - A SEER-based study of 8,281 patients:
    - Found that 5-year disease-specific survival dropped from 42.0% for level I to III disease to 30.6% for level IV [5]
  - Furthermore, level IV to V metastasis:
    - Is an independent risk factor for distant metastasis on multivariate analysis [6]
Morbidity Considerations:
- Extension to level IV is not without cost
- The American Head and Neck Society review notes that dissection of level IV:
  - Is associated with a low but possible risk of injury to the phrenic nerve or brachial plexus and increases the risk of chylous fistula [4]:
    - These risks must be weighed against the oncologic benefit, particularly in the cN0 setting where the absolute risk of level IV disease is low
Summary:
- For the cN0 neck with no intraoperative evidence of nodal disease:
  - Levels I to III remain the standard
- However, when intraoperative frozen section or final pathology reveals pN+ disease:
  - Particularly > 1 positive node or pN > pN2b:
    - The risk of level IV to V involvement rises to ~10%:
      - Justifying extension to level IV [1]
- For any preoperatively cN+ neck:
  - Level IV should be included as standard practice per ASCO and NCCN guidelines [2][3]
- Level V should be reserved for:
  - Multilevel, bulky nodal disease
References:
- 1. In Vivo Probability of Metastases in Levels IV-V in Oral Squamous Cell Carcinoma With a cN0/pN+ Situation in Levels I-Iii. Haas L, Mischkowski RA, Knape U, Król KM, Sakkas A. In Vivo (Athens, Greece). 2025 Nov-Dec;39(6):3437-3444. doi:10.21873/invivo.14141.
- 2. Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: ASCO Clinical Practice Guideline. Koyfman SA, Ismaila N, Crook D, et al. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2019;37(20):1753-1774. doi:10.1200/JCO.18.01921.
- 3. Head and Neck Cancers. National Comprehensive Cancer Network. Updated 2025-12-08.
- 4. Oral Cavity Cancer Surgical and Nodal Management: A Review From the American Head and Neck Society. Eskander A, Dziegielewski PT, Patel MR, et al. JAMA Otolaryngology– Head & Neck Surgery. 2024;150(2):172-178. doi:10.1001/jamaoto.2023.4049.
- 5. Impact of Nodal Level Distribution on Survival in Oral Cavity Squamous Cell Carcinoma: A Population-Based Study. Marchiano E, Patel TD, Eloy JA, Baredes S, Park RC. Otolaryngology–Head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery. 2016;155(1):99-105. doi:10.1177/0194599816636356.
- 6. Risk Factors for Distant Metastasis in Locoregionally Controlled Oral Squamous Cell Carcinoma: A Retrospective Study. Tomioka H, Yamagata Y, Oikawa Y, et al. Scientific Reports. 2021;11(1):5213. doi:10.1038/s41598-021-84704-w.