Larynx & Hypopharynx SCC: Definitive Treatment: overview
This algorithm covers definitive treatment of squamous cell carcinoma of the larynx and hypopharynx, branching by subsite and by early versus locally advanced disease, with a final step for adjuvant therapy by pathologic risk. Early laryngeal cancer (T1-2 N0, select T3 N0) is treated with larynx-preserving endoscopic or partial laryngectomy, which is preferred, or definitive radiotherapy. For locally advanced laryngeal cancer, options are larynx preservation with concurrent cisplatin chemoradiation (RTOG 91-11), induction TPF followed by chemoradiation or radiotherapy, and total laryngectomy with neck dissection for extensive T4a disease. Early hypopharyngeal cancer is treated with definitive radiotherapy or partial laryngopharyngectomy with neck dissection, while locally advanced hypopharyngeal disease may receive induction chemotherapy, laryngopharyngectomy, or concurrent cisplatin chemoradiation.
For resectable locally advanced tumors with PD-L1 CPS 1 or higher, the chart adds neoadjuvant pembrolizumab, surgery, postoperative radiotherapy with pembrolizumab (plus cisplatin for extranodal extension or positive margin), and adjuvant pembrolizumab (KEYNOTE-689), which improved event-free survival. After surgery, extranodal extension with or without a positive margin calls for cisplatin chemoradiation, supported by RTOG 9501.
Step by step
- Early larynx (T1-2 N0, select T3 N0): endoscopic or partial laryngectomy preferred, or definitive radiotherapy.
- Locally advanced larynx: larynx preservation with concurrent cisplatin chemoradiation (RTOG 91-11), or induction TPF then chemoradiation or radiotherapy.
- Extensive T4a larynx: total laryngectomy with neck dissection.
- Early hypopharynx (most T1 N0, select T2 N0): definitive radiotherapy, or partial laryngopharyngectomy with neck dissection.
- Locally advanced hypopharynx (T2-3 N0-3, T1 N+): induction chemotherapy then chemoradiation or surgery, laryngopharyngectomy with neck dissection, or concurrent cisplatin chemoradiation.
- Resectable locally advanced disease with PD-L1 CPS 1 or higher (in hypopharynx, excluding T2 N0 and N3): neoadjuvant pembrolizumab, surgery, then radiotherapy plus pembrolizumab (with cisplatin for extranodal extension or positive margin), then adjuvant pembrolizumab (KEYNOTE-689).
- Adjuvant, lower risk: pN0 without adverse features, observe; pN1 with no other risk features, consider radiotherapy.
- Adjuvant, higher risk: extranodal extension with or without positive margin, cisplatin chemoradiation; positive margin, re-resection or radiotherapy or chemoradiation; other risk features, radiotherapy with or without concurrent chemotherapy.
Trials behind this algorithm
- RTOG 9111 Forastiere AA et al, J Clin Oncol, 2013; PMID: 23182993
- KEYNOTE-689 Uppaluri R et al, NEJM, 2025; PMID: 40532178
- MACH-NC mena-analysis Lacas B et al, J of Radiother Oncol, 2021, PMID: 33515668
- RTOG 9501 Cooper JS et al, N Engl J Med, 2004; PMID: 15128893