Cancer of the hypopharynx is uncommon; approximately 2,500 new cases are diagnosed in the United States each year.[1] The peak incidence of this cancer occurs in males and females aged 50 to 60 years.[2] Excessive alcohol and tobacco use are the primary risk factors for hypopharyngeal cancer.[3,4] In the United States, hypopharyngeal cancers are more common in men than in women.[5] In Europe and Asia, high incidences of pharyngeal cancers, namely, oropharyngeal and hypopharyngeal, have been found among men in France, in the counties of Bas-Rhin and Herault; Switzerland, in the section of Vaud; Spain, in the Basque Country region; Slovakia; Slovenia; and India, in the cities of Bombay and Madras.[6] This cancer is extremely rare in children.[7]
Upper hypopharyngeal cancers appear to be associated more with heavy drinking and smoking, whereas the lower hypopharyngeal, or postcricoid, cancers are more often associated with nutritional deficiencies.[1,8] Although earlier reports from northern Europe, particularly from Sweden, indicated a link between Plummer-Vinson syndrome, which consisted of sideropenic anemia and epithelial changes of the aerodigestive tract, and other nutritional deficiencies in women, current cases of hypopharyngeal cancer among women are more likely to be associated with excessive use of alcohol and tobacco, rather than with deficiency diseases.[2,9-11]
Anatomically, the hypopharynx extends from the plane of the hyoid bone above to the plane of the inferior border of the cricoid cartilage below. The hypopharynx is composed of the following three parts and does not include the larynx:
The lymphatic drainage from the pharynx is into the jugulodigastric, jugulo-omohyoid, upper and middle deep cervical, and retropharyngeal nodes. In the United States and Canada, 65% to 85% of hypopharyngeal carcinomas involve the pyriform sinuses, 10% to 20% involve the posterior pharyngeal wall, and 5% to 15% involve the postcricoid area.[12] Pyriform sinus and postcricoid carcinomas are typically flat plaques with raised edges and superficial ulceration. In contrast, posterior hypopharyngeal wall tumors tend to be exophytic and are often large (i.e., 80% >5 cm) at presentation.[13] Hypopharyngeal carcinomas tend to spread within the mucosa, beneath intact epithelium, and are prone to skip metastasis and to resurface at various locations remote from the primary site.[1,13] Because of this fact and the abundant lymphatic network of the region, a localized hypopharyngeal tumor is the exception.[1]
Almost all hypopharyngeal cancers are mucosal squamous cell carcinomas (SCCs).[1] Multiple primary tumors are not uncommon. Approximately 25% of patients in a retrospective study of 150 cases were found to have second primary tumors.[14] Field cancerization may be responsible, in part, for the multiple, synchronous, primary malignant neoplasms that occur in patients with hypopharyngeal cancer.[1,14-16] The concept of field cancerization, originally described in 1953, proposes that tumors develop in a multifocal fashion within a field of tissue that has been chronically exposed to carcinogens.[17]
Clinically, cancers of the hypopharynx tend to be aggressive and demonstrate a natural history that is characterized by diffuse local spread, early metastasis, and a relatively high rate of distant spread. More than 50% of patients with hypopharyngeal cancer have clinically positive cervical nodes at the time of presentation. In 50% of these individuals, a neck mass is the presenting symptom.[2,18,19] In a retrospective study of 78 cases of hypopharyngeal cancer, other symptoms in addition to a neck mass (25.6%) included dysphagia (46.1%), odynophagia (44.8%), voice change (16.3%), and otalgia (14.2%).[2] A voice change resulting from pyriform sinus or postcricoid lesions is a late symptom that usually indicates invasion into the larynx or the recurrent laryngeal nerve.[1]
In a large retrospective study of patients with SCC of the larynx and hypopharynx, 87% of patients with pyriform sinus SCC were found to have stage III or stage IV disease; 82% of patients with SCC of the posterior pharyngeal wall were found to have stage III or stage IV disease.[20] As many as 17% of hypopharyngeal SCCs may be associated with distant metastases when clinically diagnosed.[20] This is quite different from the rate of distant metastasis detected at autopsy, which has been reported to be as high as 60%.[21] A relatively high incidence of delayed regional (i.e., 2 or more years after completion of primary therapy) and distant metastatic disease in hypopharyngeal SCC is related to the advanced stage of the disease at diagnosis. Almost 33% of pyriform sinus tumors may be associated with delayed regional metastases.[20]
The treatment of hypopharyngeal cancer is controversial, in part because of its low incidence and the inherent difficulty in conducting adequately powered, prospective, randomized clinical studies.[22] Therefore, it is difficult to define the ideal therapy for a specific site or stage of hypopharyngeal cancer. In general, both surgery and radiation therapy are the mainstays of most curative efforts. In recent years, chemotherapy has been added to the treatment strategies for selected advanced presentations of hypopharyngeal cancer.[23] In pyriform sinus cancer, neoadjuvant chemotherapy followed by radiation therapy may achieve larynx preservation without jeopardizing survival.[24]
Chronic pulmonary and hepatic diseases related to the excessive use of tobacco and alcohol are found in patients with hypopharyngeal cancer. Recognition of these comorbidities is essential when planning appropriate treatment.[1] The primary prognostic factors for hypopharyngeal SCC are the following:[1,25,26]
Factors that contribute to an overall poor prognosis with hypopharyngeal SCC include the following:
In many patients, a poor prognosis is related to poor overall health.[13] The most common cause of failure of treatment of the primary tumor is local and/or regional recurrence. Most treatment failures occur within the first 2 years following definitive therapy. The burden of lymph node metastases may yield information of prognostic value. In a retrospective study, a total volume of metastatic disease of more than 100 cm3 indicated a particularly poor prognosis.[25]
In addition to the risk of delayed regional metastases, the risk of developing a second primary tumor in patients with tumors of the upper aerodigestive tract has been estimated to be 4% to 7% per year.[20,26-28] Because of these risks, surveillance of patients with hypopharyngeal cancer should be lifelong.
SCC of the hypopharynx has not been associated with any specific chromosomal or genetic abnormalities;[13] however, loss of chromosome 18 was observed in 57% of hypopharyngeal tumors in one study.[29] Several other studies have emphasized the importance of chromosome 11q13 amplification, which may be related to the presence of nodal metastases, greater local aggressiveness, and a higher incidence of tumor recurrence.[30-33]
Almost all hypopharyngeal cancers are epithelial in origin, predominantly squamous cell (i.e., epidermoid) carcinomas (SCCs), and may be preceded by various precancerous lesions.[1,2] Rare types of hypopharyngeal carcinomas include the following:
Nonepithelial tumors, including lymphomas, sarcomas, and melanomas, require separate consideration and are not included in the staging and treatment options discussed in this summary.[1,3-8]
Invasive SCCs are usually moderately or poorly differentiated and invariably stain positively for keratin.[1] In situ carcinoma is often seen adjacent to invasive SCC.[1,9]
The term, leukoplakia, should be used only as a clinically descriptive term meaning that the observer sees a white patch that does not rub off, the significance of which depends on the histological findings.[10] Based on this description, leukoplakia can range from hyperkeratosis to an actual early invasive carcinoma or may represent only a fungal infection, lichen planus, or other benign oral disease.
The staging systems are all clinical staging and are based on the best possible estimate of the extent of disease before treatment. The assessment of the primary tumor is based on inspection and palpation, when possible, and by both indirect mirror examination and direct endoscopy. The tumor must be confirmed histologically, and any other pathological data obtained from a biopsy may be included. Additional radiographic studies may be included. As an adjunct to clinical examination, computed tomography and/or magnetic resonance imaging are needed for an accurate staging of laryngeal and hypopharyngeal carcinomas because both cross-sectional imaging modalities are known to reliably evaluate deep tumor infiltration.[1-3] The appropriate nodal drainage areas are examined by careful palpation. If a patient relapses, complete restaging must be done to select the appropriate additional therapy.
The AJCC has designated staging by TNM (tumor, node, metastasis) classification to define hypopharyngeal cancer.[4]
| T Category | T Criteria |
|---|---|
| aReprinted with permission from AJCC: Oropharynx (p16-) and Hypopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 123–35. | |
| bCentral compartment soft tissue includes prelaryngeal strap muscles and subcutaneous fat. | |
| TX | Primary tumor cannot be assessed. |
| Tis | Carcinoma in situ. |
| T1 | Tumor limited to one subsite of hypopharynx and/or ≤2 cm in greatest dimension. |
| T2 | Tumor invades more than one subsite of hypopharynx or an adjacent site, or measures >2 cm but ≤4 cm in greatest dimension without fixation of hemilarynx. |
| T3 | Tumor >4 cm in greatest dimension or with fixation of hemilarynx or extension to esophageal mucosa. |
| T4 | Moderately advanced and very advanced local disease. |
| ‒T4a | Moderately advanced local disease. Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, esophageal muscle, or central compartment soft tissue.b |
| ‒T4b | Very advanced local disease. Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures. |
| N Category | Clinical N (cN) Criteria | Pathological N (pN) Criteria |
|---|---|---|
| ENE = extranodal extension. | ||
| aReprinted with permission from AJCC: Oropharynx (p16-) and Hypopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 123–35. | ||
| Note: A designation of U or L may be used for any N category to indicate metastasis above the lower border of the cricoid (U) or below the lower border of the cricoid (L). Similarly, clinical and pathological ENE should be recorded as ENE(‒) or ENE(+). | ||
| NX | Regional lymph nodes cannot be assessed. | Regional lymph nodes cannot be assessed. |
| N0 | No regional lymph node metastasis. | No regional lymph node metastasis. |
| N1 | Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension and ENE(‒). | Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension and ENE(‒). |
| N2 | Metastasis in a single ipsilateral node >3 cm but ≤6 cm in greatest dimension and ENE(‒); or metastases in multiple ipsilateral lymph nodes, none >6 cm in greatest dimension and ENE(‒); or in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension and ENE(‒). | Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension and ENE(+); or >3 cm but ≤6 cm in greatest dimension and ENE(‒); or metastases in multiple ipsilateral lymph nodes, none >6 cm in greatest dimension and ENE(‒); or in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension and ENE(‒). |
| ‒N2a | Metastasis in a single ipsilateral node >3 cm but ≤6 cm in greatest dimension and ENE(‒). | Metastasis in single ipsilateral node ≤3 cm in greatest dimension and ENE(+); or a single ipsilateral node >3 cm but ≤6 cm in greatest dimension and ENE(‒). |
| ‒N2b | Metastases in multiple ipsilateral nodes, none >6 cm in greatest dimension and ENE(‒). | Metastases in multiple ipsilateral nodes, none >6 cm in greatest dimension and ENE(‒). |
| ‒N2c | Metastases in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension and ENE(‒). | Metastases in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension and ENE(‒). |
| N3 | Metastasis in a lymph node >6 cm in greatest dimension and ENE(‒); or metastasis in any node(s) and clinically overt ENE(+). | Metastasis in a lymph node >6 cm in greatest dimension and ENE(‒); or metastasis in a single ipsilateral node >3 cm in greatest dimension and ENE(+); or multiple ipsilateral, contralateral, or bilateral nodes, any with ENE(+); or a single contralateral node of any size and ENE(+). |
| ‒N3a | Metastasis in a lymph node >6 cm in greatest dimension and ENE(‒). | Metastasis in a lymph node >6 cm in greatest dimension and ENE(‒). |
| ‒N3b | Metastasis in any node(s) and clinically overt ENE(+). | Metastasis in a single ipsilateral node >3 cm in greatest dimension and ENE(+); or multiple ipsilateral, contralateral, or bilateral nodes, any with ENE(+); or a single contralateral node of any size and ENE(+). |
| M Category | M Criteria |
|---|---|
| aReprinted with permission from AJCC: Oropharynx (p16-) and Hypopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 123–35. | |
| M0 | No distant metastasis. |
| M1 | Distant metastasis. |
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Oropharynx (p16-) and Hypopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 123–35. | ||
| 0 | Tis, N0, M0 | Tis = Carcinoma in situ. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Oropharynx (p16-) and Hypopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 123–35. | ||
| I | T1, N0, M0 | T1 = Tumor limited to one subsite of hypopharynx and/or ≤2 cm in greatest dimension. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Oropharynx (p16-) and Hypopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 123–35. | ||
| II | T2, N0, M0 | T2 = Tumor invades more than one subsite of hypopharynx or an adjacent site, or measures >2 cm but ≤4 cm in greatest dimension without fixation of hemilarynx. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis; ENE = extranodal extension. | ||
| aReprinted with permission from AJCC: Oropharynx (p16-) and Hypopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 123–35. | ||
| III | T3, N0, M0 | T3 = Tumor >4 cm in greatest dimension or with fixation of hemilarynx or extension to esophageal mucosa. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| III | T1, T2, T3, N1, M0 | T1, T2, T3 = See Table 1. |
| N1 = Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension and ENE(‒). | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis; ENE = extranodal extension. | ||
| aReprinted with permission from AJCC: Oropharynx (p16-) and Hypopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 123–35. | ||
| bCentral compartment soft tissue includes prelaryngeal strap muscles and subcutaneous fat. | ||
| IVA | T4a, N0, N1, M0 | T4a = Moderately advanced local disease. Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, esophageal muscle, or central compartment soft tissue.b |
| N0 = No regional lymph node metastasis. | ||
| N1 = Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension and ENE(‒). | ||
| M0 = No distant metastasis. | ||
| IVA | T1, T2, T3, T4a, N2, M0 | T1, T2, T3, T4a = See Table 1. |
| N2 = See Table 2. | ||
| M0 = No distant metastasis. | ||
| IVB | Any T, N3, M0 | Any T = See Table 1. |
| N3 = See Table 2. | ||
| M0 = No distant metastasis. | ||
| IVB | T4b, Any N, M0 | T4b = Very advanced local disease. Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures. |
| Any N = See Table 2. | ||
| M0 = No distant metastasis. | ||
| IVC | Any T, Any N, M1 | Any T = See Table 1. |
| Any N = See Table 2. | ||
| M1 = Distant metastasis. | ||
Hypopharyngeal cancer usually does not cause symptoms until late in the course of the disease. Coupled with the high incidence of early metastasis, survival rates for carcinoma of the hypopharynx are perhaps the lowest of all cancer sites in the head and neck.
No single therapeutic regimen offers a superior survival advantage over other regimens. Although the literature highlights various therapeutic options, few reports present any valid comparative studies. The ultimate therapeutic choice will depend on a careful review of each individual case, paying attention to the staging of the neoplasm, the general physical condition of the patient, the emotional status of the patient, the experience of the treating team, and the available treatment facilities.[1,2]
Except for very early stage (T1) cancers of this region, treatment has primarily been surgery, usually followed with postoperative radiation therapy (PORT). Some early stage (T1 and T2), low-volume, exophytic pyriform sinus carcinomas have been successfully treated with radiation therapy alone.[3-5] Single-modality therapy of advanced-stage hypopharyngeal cancer, with either surgery or radiation therapy, has resulted in consistently poor survival.[6-8]
Combined-modality treatment should be considered for patients with stage III or stage IV disease.[4,6,9,10] When used with surgery, radiation therapy is typically administered postoperatively. In selected advanced cases, alternative strategies using neoadjuvant chemotherapy and radiation therapy may increase the chance for local control as much as resection and PORT.[4]
A review of published clinical results of radical radiation therapy for head and neck cancer suggests a significant loss of local control when radiation therapy was prolonged; therefore, lengthening of standard treatment schedules should be avoided whenever possible.[11,12]
Chronic pulmonary and hepatic diseases related to excessive tobacco and alcohol use are common in patients with head and neck cancer; recognition of these comorbidities is essential when planning appropriate treatment.[6] Patients who smoke during radiation therapy appear to have lower response rates and shorter survival durations than those who do not.[13] Consequently, patients should be counseled to stop smoking before beginning radiation therapy. Evidence has demonstrated a high incidence (i.e., >30%–40%) of hypothyroidism in patients who have received external-beam radiation therapy to the entire thyroid gland or to the pituitary gland. Thyroid function testing of patients should be considered before therapy and as part of posttreatment follow-up.[14,15]
The DPYD gene encodes an enzyme that catabolizes pyrimidines and fluoropyrimidines, like capecitabine and fluorouracil. An estimated 1% to 2% of the population has germline pathogenic variants in DPYD, which lead to reduced DPD protein function and an accumulation of pyrimidines and fluoropyrimidines in the body.[16,17] Patients with the DPYD*2A variant who receive fluoropyrimidines may experience severe, life-threatening toxicities that are sometimes fatal. Many other DPYD variants have been identified, with a range of clinical effects.[16-18] Fluoropyrimidine avoidance or a dose reduction of 50% may be recommended based on the patient's DPYD genotype and number of functioning DPYD alleles.[19-21] DPYD genetic testing costs less than $200, but insurance coverage varies due to a lack of national guidelines.[22] In addition, testing may delay therapy by 2 weeks, which would not be advisable in urgent situations. This controversial issue requires further evaluation.[23]
Except for the very early T1 cancers of this region, treatment has been primarily surgery, usually followed with postoperative radiation therapy. Because these tumors are clinically silent until they reach advanced stages, it is very unusual to diagnose them at the T1 N0 stage. In most available retrospective reviews, T1 N0 cases represent only 1% to 2% of all patients seen. In the case of exophytic T1 N0 lesions, radiation therapy alone may be considered.[1,2]
Treatment options for stage I hypopharyngeal cancer include the following:
In very selected cases of pyriform sinus cancers, that is, those arising in the upper lateral wall, a partial laryngopharyngectomy may be successfully used to preserve vocal function. All groups who use radiation therapy advocate high-dose treatment to the primary site and to both sides of the neck to include the retropharyngeal and lateral cervical nodes.[1]
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Treatment has been primarily surgery, which is usually followed with postoperative radiation therapy (PORT). Because these tumors are clinically silent until they reach advanced stages, it is very unusual to diagnose these tumors at the T2 N0 stage.
Treatment options for stage II hypopharyngeal cancer include the following:
In very selected cases of pyriform sinus cancers, that is, those arising in the upper medial wall, a partial laryngopharyngectomy may be successfully used to preserve vocal function. In T2 cases, PORT has been given in combination with surgery in an effort to improve the local control rates of surgery alone. There are advocates of preoperative radiation therapy, but all groups giving radiation therapy advocate high-dose treatment to the primary site and to both sides of the neck to include the retropharyngeal and lateral cervical nodes.[1,2]
The use of neoadjuvant chemotherapy to increase organ preservation has also been advocated. In a prospective randomized trial (GORTEC-TREMPLIN trial [NCT00169247]), the European Organisation for the Research and Treatment of Cancer compared surgery plus PORT with neoadjuvant chemotherapy (i.e., cisplatin plus fluorouracil) followed by radiation therapy in responding patients. 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 and overall survival 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. These data have not been confirmed by other phase III trials but suggest that larynx preservation may be feasible without jeopardizing survival.[4][Level of evidence A1 and A3]
Most neoadjuvant chemotherapy clinical trials have included patients with stage II hypopharyngeal carcinoma because of the low survival rates for this population.[5]
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
The management of patients with stage III hypopharyngeal cancer 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 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.
Treatment options for stage III hypopharyngeal cancer include the following:
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.
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]
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.
For more information about treatment options for stage III hypopharyngeal cancer, see Treatment Options for Unresectable Stage IV Hypopharyngeal Cancer.
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
The management of patients with resectable hypopharyngeal cancer 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 within 3 to 4 weeks following resection.
Details of surgical procedures and 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.
Treatment options for resectable stage IV hypopharyngeal cancer include the following:
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 Research and Treatment of Cancer compared surgery plus PORT with induction chemotherapy (i.e., cisplatin plus fluorouracil [5-FU]) followed by radiation in responding patients.[4] 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.[4][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.[5][Level of evidence A1 and A3] Although organ preservation was not discussed, chemotherapy in combination with radiation therapy without surgery should not be considered standard treatment.
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 who received radiation therapy plus concurrent chemotherapy.[6][Level of evidence A1] In another study, primary site preservation was improved, though OS was not improved when chemotherapy was given concomitantly with radiation therapy.[7,8]
Treatment options for unresectable stage IV hypopharyngeal cancer include the following:
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.[18][Level of evidence B4] Patients who received concurrent chemotherapy had a greater survival benefit than those who received induction chemotherapy.
These patients should have a careful head and neck examination, looking for recurrence monthly for the first posttreatment year, every 2 months for the second year, every 3 months the third year, and every 6 months thereafter.
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Treatment options for metastatic and recurrent hypopharyngeal cancer include the following:
These patients should have a careful head and neck examination, looking for recurrence monthly for the first posttreatment year, every 2 months for the second year, every 3 months the third year, and every 6 months thereafter.
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Treatment Option Overview for Hypopharyngeal Cancer
Added Fluorouracil Dosing as a new subsection.
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult hypopharyngeal cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Hypopharyngeal Cancer Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”
The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Hypopharyngeal Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/head-and-neck/hp/adult/hypopharyngeal-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389199]
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.
More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s Email Us.