Who should get Adjuvant Cisplatin‐Radiation Therapy (RT) after Surgery for Head and Neck Squamous Cell Carcinoma (HNSCC)?

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • High-risk triggers (guideline-concordant):
    • Positive margin (R+) or close margin (institutional cutoffs commonly < 1 to 5 mm)
    • Extranodal extension (ENE / ECS +) in any positive node
  • Rationale:
    • These were the features driving benefit from adding concurrent cisplatin to postoperative RT in the pivotal randomized trials and follow-ups PMC+2PMC+2
  • Pivotal trials:
    • EORTC 22931 (Bernier, NEJM 2004):
      • Design: 
        • Post-op RT alone (66 Gy) vs RT + cisplatin 100 mg / m² q3wk ×3
      • 5-yr outcomes (KM estimates): 
        • OS 53% vs 40%
        • PFS 47% vs 36%:
          • Both favoring CRT
        • Reported hazard ratios (RT + Cisplatin vs RT): 
          • OS HR ≈ 0.70–0.75
          • PFS HR 0.75:
            • Benefit across most high-risk features
      • Takeaway: 
    • RTOG 9501 (Cooper, NEJM 2004; 10-yr update 2012):
      • Design: 
        • Post-op RT alone (60 Gy/6 wk) vs RT + cisplatin 100 mg / m² on days 1, 22, 43
      • Overall cohort (10-yr KM): 
        • LRF 28.8% vs 22.3% (p=0.10)
        • DFS 19.1% vs 20.1% (p=0.25)
        • OS 27.0% vs 29.1% (p=0.31)
          • No significant advantage in the unselected population
        • Key subset (pre-specified high-risk: R+ and / or ENE+):
          • LRF 33.1% (RT) vs 21.0% (CRT), p=0.02
          • DFS 12.3% vs 18.4%, p=0.05
          • OS 19.6% vs 27.1%, p=0.07 (trend)
          • KM curves:
            • Markedly diverge in this subgroup, establishing R+ / ENE+ as the clearest indication for cisplatin-RT PubMed+1
    • Cross-trial comparative / pooled insight:
      • Bernier et al., Head & Neck 2005 compared EORTC 22931 and RTOG 9501:
        • Concluded the greatest benefit from CRT accrues to patients with:
          • ENE+ and / or positive margins PubMed+1
      • Updated combined analysis (2025):
        • Again supports an OS benefit for CRT across the combined cohorts:
          • While noting competing non-cancer mortality:
            • Still, ENE and / or R+ remain the most reproducible risk features prompting CR PubMed+1
  • How to apply at tumor board:
    • Offer adjuvant cisplatin-RT when any of the following are present::
      • Positive margin:
        • R1:
          • Re-resection preferred when feasible, otherwise CRT
      • Close margin:
        • Where institutional policy treats as high risk:
          • Commonly < 1 to 5 mm, site-dependent
      • ENE / ECS+ in a lymph node (any extent) PMC
      • Intermediate-risk (e.g., PNI, LVI, pT3, pN2 without ENE, multiple nodes but ENE-negative):
        • RT alone remains standard:
    • Cisplatin fitness: 
      • If contraindicated (CrCl < 60 mL/min, grade ≥ 2 SNHL, neuropathy, poor PS):
        • Use RT alone or alternative systemic partner per site-specific guidance:
          • But the randomized survival gain post-op is with cisplatin ACS Publications
  • Quick “exam-pearl” summaries:
    • EORTC 22931: 
    • RTOG 9501 (10-yr): 
      • Whole cohort:
        • No OS benefit
        • R+ / ENE+ subset: 
          • Better LRC and DFS, OS trend with CRT:
            • This is the clinical trigger PubMed
      • Define “close” carefully:
        • Many centers treat < 5 mm (some < 3 mm or < 1 mm by subsite) as high-risk when re-resection isn’t possible PMC+1
  • Bottom line:
    • After resection of LA-HNSCC:
      • Adjuvant cisplatin-RT is indicated for ENE+ and positive (or institutionally “close”) margin:
        • The exact groups where the Kaplan–Meier curves in RTOG 9501 and EORTC 22931 show the clearest advantage for adding chemotherapy to RT
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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