Cancer Health Center

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

The management of this group of patients is complex and requires multidisciplinary input to establish the optimal treatment regimen. New surgical techniques and reconstructions using the gastric pull-up operation or free jejunal transfers have greatly reduced the morbidity associated with resection of these tumors and have almost eliminated the need for multistage reconstructions. This has greatly aided the combined treatment regimens because these patients have a high likelihood of beginning postoperative radiation therapy (PORT) within 3 to 4 weeks following resection.

Details of surgical procedures and their modifications of radiation fields or dosage schedules are not specifically designated here because of legitimate variations in techniques that, according to various retrospective data, give similar survival results in different treatment centers. This group of patients should be managed by surgeons and radiation oncologists who are skilled in the multiple procedures and techniques available and who are actively and frequently involved in the care of these patients.

Standard treatment options:

1. 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.[1,2,3]
2. Neoadjuvant chemotherapy as given in clinical trials has been used to shrink tumors and render them more definitively treatable with either surgery or radiation. Chemotherapy is given prior to the other modalities, hence the designation, neoadjuvant, to distinguish it from standard adjuvant therapy, which is given after or during definitive therapy with radiation or after surgery. Many drug combinations have been used in neoadjuvant chemotherapy. 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 (NCT00169247), the European Organization for the Treatment and Research of Cancer is comparing surgery plus PORT to induction chemotherapy (i.e., cisplatin plus 5-fluorouracil [5-FU]) followed by radiation in responding patients.[5] Local and regional failures are similar in both groups. Although median survival is 25 months in the immediate surgery arm of the study and 44 months in the induction chemotherapy arm (P = .006), 5-year disease-free and overall survival (OS) are the same. A functional larynx is preserved in 42% of patients at 3 years and 35% at 5 years in patients who are receiving induction chemotherapy.[5][Level of evidence: 1iiA,1iiC] 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: 1iiA,1iiC] Although organ preservation was not discussed in this study, chemotherapy in combination with radiation therapy without surgery should not be considered standard.
3. Patients with stage III hypopharyngeal cancer should be considered for treatment with 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 disease-free survival (P < .02) were better in the group of patients receiving radiation therapy plus concurrent chemotherapy.[7][Level of evidence:1iiA] In another study, primary site preservation was improved, though OS was not improved when chemotherapy was administered concomitantly with radiation therapy.[8,9]