Main prognostic factor tailoring the treatment for hypopharyngeal cancer (HC) is the disease stage (Table 8.1). Other factors include age (elderly poor), gender (male poor), tumor location (pyriform sinus apex, postcricoid region, and two- or three-wall tumors poor), and size and number of involved nodes (multiple and N3 poor) [1–3]. Definitive RT or partial laryngopharyngectomy (open or endoscopic) plus ipsi- or bilateral neck dissection (ND) are the equally effective treatment options for T1N0 and selected T2N0 patients. Salvage surgery and ND are indicated in patients with clinical or metabolic residual disease following definitive RT. In surgically treated patients with adverse features, re-resection or adjuvant therapy is indicated. For patients with ECE ± positive margins, CRT is the standard of care (category 1). In patients with positive margins, re-resection or adjuvant RT is indicated, and CRT must be considered for only T2 tumors. For patients with other risk factors, adjuvant RT or CRT must be considered.

Induction chemotherapy is the recommended treatment option for T1–T2 N+ and T3N0–N3 patients, and further treatment is determined by the response, namely, complete (CR), partial (PR), and less than PR (<PR). If CR is achieved at primary site with improved or stable disease in the neck, definitive RT (category 1) or CRT (category 2B) are the current recommendations.

Patients with < PR at primary disease site with improved or stable disease in neck after induction chemotherapy are treated with either CRT (category 2B) or surgery. Salvage surgery is indicated if residual disease exists after CRT. RT is indicated in patients treated with surgery and no evident adverse factors. Patients with ECE and/or positive margins should undergo CRT (category 1). If other adverse factors exist, RT or CRT should be considered.

Surgery is the recommended up-front treatment for T2N+, T3N0–N3, and T1N+ patients with < PR at primary disease site after induction chemotherapy, and further treatment is determined by the status of adverse factors. If no adverse factor exists, RT is recommended. The presence of ECE and/or positive margins is an indication for CRT (category 1). If other adverse factors exist, RT or CRT should be considered.

Patients with T4a and N0–N3 should preferentially be treated with surgery followed by RT or CRT. However, induction chemotherapy followed by RT/CRT (surgery reserved for salvage), and definitive CRT is another treatment option with category 3 evidence. Postsurgical use of RT/CRT or salvage surgery after CRT is determined by the status of adverse factors. Salvage surgery and ND are indicated in patients with clinical or metabolic residual disease following CRT. Surgically treated patients with ECE and/or positive margins should undergo CRT (category 1). If other adverse factors exist, RT or CRT should be considered. Patients with progressive disease should be treated with CRT (category 2B) or surgery depending on the choice of initial treatment modality.

As a general rule, the treatment of choice is the one that proves the highest locoregional tumor control with the highest chance for preservation of respiration, deglutition, and phonation functions. In cases with T1–T2 N0 disease, both the conservative surgery and RT have similar efficacy. Vocal cord fixation by pyriform sinus tumor via invasion of the larynx portends relatively poorer outcome with definitive RT. Large nodal mass in the neck impacts the need for combination of surgery followed by RT for higher cure chance compared to either modality alone.

Type of primary resection may vary from partial laryngopharyngectomy to extremely aggressive laryngopharyngoesophagectomy and adjacent structures if involved. In addition to primary tumor resection, surgical treatment includes at least unilateral ND which is followed by RT or CRT. Conservative surgery is contraindicated in patients with:

For small T1 and T2 lesions, 66–70 Gy RT alone may control tumor in nearly 65 % of all patients (Table 8.2).

As postoperative pharyngeal or cutaneous healing is delayed by preoperative high-dose RT (60–66 Gy), to prevent or minimize postoperative complications, a dose of 45–50 Gy is recommended if RT is used in neoadjuvant setting. High-dose RT (60–66 Gy) is better tolerated when administered postoperatively with a healing period of at least 4 weeks. However, if no contraindication exists, postoperative RT should commence between 4 and 6 weeks postoperatively for better locoregional control. For aryepiglottic fold and pyriform sinus tumors, combined surgery and postoperative RT proves higher rates of 5-year disease-free and overall survival rates compared to RT or surgery alone [3].

Results of nonrandomized series demonstrated that it was possible to the spare larynx in 40–65 % patients (with/without locoregional and survival advantage) treated with induction chemotherapy followed by high-dose RT (65–75 Gy) compared to surgery followed by RT [4–8]. Based on these promising outcomes, EORTC 24891 (the European Organization for Research and Treatment of Cancer Head and Neck Cooperative Group) conducted a phase 3 randomized trial of the larynx preservation [9, 10]. This study enrolled 202 patients with locally advanced hypopharyngeal cancer (pyriform sinus or hypopharyngeal aspect of aryepiglottic fold), whose treatment would be necessitated total laryngectomy to one of two arms: arm A, total laryngectomy and partial pharyngectomy followed by adjuvant RT (n = 99), and arm B, 2–3 cycles of induction cisplatin/5-fluorauracil followed by 70 Gy RT (7 weeks) in patients with complete response. Complete response was defined as total return of laryngeal mobility and macroscopic disappearance of gross tumor. Complete response was achieved in 54 % cases enrolled to induction chemotherapy arm. Complete response rates were observed to be significantly associated with T stage. At a median follow-up of 51 months (3–106 months), there was no statistically significant difference between arms A and B in terms of local (88 % vs. 83 %; p > 0.05) and regional (81 % vs. 77 %; p > 0.05) control rates. However, distant metastasis-free survival rates were significantly higher in arm B (64 % vs. 75 %; p = 0.04). As depicted in Table 8.3, median and 3-year survival rates were favoring induction chemotherapy arm, but this survival advantage disappeared at 5 years. Considering the larynx preservation, the larynx was maintained in 42 and 35 % patients at 3- and 5-year time points.