Treatment Options for Stage III Hypopharyngeal Cancer

The combination of surgery and radiation, most often postoperative as seen in a follow-up study of preoperative versus PORT (RTOG-7303), has become the usual form of therapy for this group of patients in the United States.[1-3]

Neoadjuvant chemotherapy is commonly used to treat patients who present with advanced disease to improve locoregional control or survival, despite the lack of data from randomized prospective trials.[4]The use of neoadjuvant chemotherapy to increase organ preservation has also been advocated. In a prospective randomized trial (GORTEC-TREMPLIN [NCT00169247]), the European Organisation for the Treatment and Research of Cancer compared surgery plus PORT with induction chemotherapy (i.e., cisplatin plus fluorouracil [5-FU]) followed by radiation in responding patients.[5] Local and regional failures were similar in both groups. Although median survival was 25 months in the immediate surgery arm of the study and 44 months in the induction chemotherapy arm (P = .006), 5-year disease-free survival (DFS) and overall survival (OS) were the same. A functional larynx was preserved in 42% of patients at 3 years and 35% at 5 years in patients who received induction chemotherapy.[5][Level of evidence A1 and A3]In contrast to this, another randomized prospective trial has demonstrated a statistically significant survival advantage for patients undergoing chemotherapy (i.e., cisplatin plus 5-FU) followed by laryngopharyngectomy and PORT when compared with chemotherapy and radiation therapy.[6][Level of evidence A1 and A3] Although organ preservation was not discussed in this study, chemotherapy in combination with radiation therapy without surgery should not be considered standard treatment.

Patients with stage III hypopharyngeal cancer should consider combined postoperative, adjuvant radiation therapy and chemotherapy. In a prospective randomized trial, postoperative adjuvant radiation therapy alone was compared with postoperative adjuvant radiation therapy plus concurrent chemotherapy. Both the OS (P < .01) and the DFS (P < .02) were better in the group of patients receiving radiation therapy plus concurrent chemotherapy.[7][Level of evidence A1] In another study, primary site preservation was improved, though OS was not improved when chemotherapy was administered concomitantly with radiation therapy.[8,9]

Chemotherapy combined with radiation therapy for patients with locally advanced disease (under clinical evaluation).[10-12] Concurrent chemotherapy is a standard treatment option for patients with locally advanced (stage III and stage IV) hypopharyngeal cancer. A meta-analysis of 93 randomized prospective head and neck cancer trials published between 1965 and 2000 showed a 4.5% absolute survival advantage in the subset of patients who received chemotherapy and radiation therapy.[13][Level of evidence B4] Patients who received concurrent chemotherapy had a greater survival benefit than those who received induction chemotherapy.