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Management of the Patients with Hypopharyngeal Cancer 65

65

Tohoku J. Exp. Med., 2005, 205, 65-77

Received February 17, 2004; revision accepted for publication November 16, 2004.Address for reprints: Masaru Tateda, M.D., Department of Head and Neck Surgery, Miyagi Cancer Center

Hospital, 47-1 Nodayama, Medeshima-Shiote, Natori 981-1293, Japan.e-mail: [email protected]

Management of the Patients with Hypopharyngeal Cancer: Eight-Year Experience of Miyagi Cancer Center in Japan

MASARU TATEDA, KIYOTO SHIGA,1 HUMIAKI YOSHIDA, SHIGERU SAIJO, JYUNKICHI YOKOYAMA,2 HITOSHI NISHIKAWA, YUKINORI ASADA, KAZUTO MATSUURA and TOSHIMITU KOBAYASHI

1

Department of Head and Neck Surgery, Miyagi Cancer Center, Natori, 1Department of Otolaryngology, Head and Neck Surgery, Tohoku University School of Medicine, Sendai, and 2Department of Head and Neck Surgery, Tochigi Cancer Center, Utsunomiya, Japan

TATEDA, M., SHIGA, K., YOSHIDA, H., SAIJO, S., YOKOYAMA, J., NISHIKAWA, H., ASADA, Y., MATSUURA, K. and KOBAYASHI, T. Management of the Patients with Hypopharyngeal Cancer: Eight-Year Experience of Miyagi Cancer Center in Japan. Tohoku J. Exp. Med., 2005, 205 (1), 65-77 ── The aim of this study is to evaluate the results of treatment for hypopharyngeal cancer and indicate the future prospect of the treatment. Seventy-four pa-tients with squamous cell carcinoma of the hypopharynx admitted to Miyagi Cancer Center from 1993 through 2000 are reviewed. Sixty-four patients received radical treatment, and 10 patients received palliative treatment or no treatment. The cancer was advanced (stages III and IV) in 82% of all the patients. The overall 5-year survival rate of all the patients was 38%. The overall 5-year survival rate of 64 patients received radical treatment was 43%. The ten patients who received palliative treatment or no treatment died of cancer within 16 months. Fifty-two out of the 74 patients underwent neck dissection for the neck lymph node involvement; forty of the 52 patients underwent ipsilateral neck dissection and 12 underwent bilateral neck dissection. Four out of the 40 patients, who underwent ipsilat-eral neck dissection alone, developed late contralateral regional recurrence but were suc-cessfully treated by contralateral neck dissection at the time of recurrence. Twenty-three out of 74 patients had multiple primary cancers synchronously or metachronously (31%). Cause of the death of six patients out of 74 patients was confirmed to be primary cancers other than hypopharyngeal cancer, as judged by physicians in other department or other hospitals. Most of the patients died due to distant metastasis from hypopharyngeal cancer or other primary cancers. We therefore conclude that contralateral elective neck dissection which is frequently chosen for the treatment of hypopharyngeal cancer surgery is unneces-sary. Even if locoregional control is accomplished, distant metastasis or multiple primary cancers emerge and make prognosis poor. To improve the prognosis, we should develop some strategy against hypopharyngeal cancer for each patient. New strategies including chemoprevention and surgery against distant metasistasis are necessary. ──── hypopha-ryngeal cancer; distant metastasis; multiple primary cancers; elective neck dissection© 2005 Tohoku University Medical Press

M. Tateda et al.66 Management of the Patients with Hypopharyngeal Cancer 67

sification of the International Union Against Cancer (UICC 1997). pTN classification was based on the path-ological findings. The T classification is classified by the expanse and the invasive region of the tumor. N0 is no

It is generally accepted that the prognoses of the patients with hypopharyngeal cancer are poor. The main cause of poor prognosis has been high frequency of advanced cancer. Although radical surgery with subsequent reconstruction of the cer-vical esophagus by free jejunum transfer has be-come a relatively easy procedure for advanced cancer recently, the survival rate in such cases re-mains fairly poor. In hypopharyngeal cancer, there are various problematic issues such as the high frequency of distant metastasis, occurrence of multiple primary cancers (Schwartz et al. 1994; Ogawa et al. 1999), choice of therapy such as ra-diation and surgery for the primary lesion, therapy for retropharyngeal lymph node (Hasegawa and Matsuura 1994), and indication for contralateral elective neck dissection (Nishijima et al. 1991; Anderson et al. 1996; Lassaletta et al. 2002). We thought that these many problems are compound and make survival rate decline. At our institution, in principal, the choice of radical therapies of the primary hypopharyngeal cancer lesion is radiation with chemotherapy or surgery, including partial pharyngectomy, and neck lymph node metastasis is treated by neck dissection with no contralateral elective neck dissection. Additional therapy is conducted in patients with multiple lymph nodes metastasis. Not all patients with hypopharyngeal cancer undergo radical treatment. Although there are many reports concerning each radical treat-ment (Pingree et al. 1987; Ho et al. 1993; Frank et al. 1994; Spector et al. 1995; Axon et al. 1997; Eckel et al. 2001; Godballe et al. 2002; Barzan et al. 2002), general results of the treatment of hypo-pharyngeal cancer are unclear. Therefore we ana-lyzed the results of treatment in 74 patients with hypopharyngeal cancer retrospectively to clarify each problem, and herein discuss appropriate treatment strategies for future prospect.

SUBJECTS AND METHODS

Seventy-four patients with squamous cell carcinoma of the hypopharynx who were admitted to our hospital for the first time from March 1993 through December 2000 were reviewed. We analyzed the treatment method, results of treatment and survival rate. The TNM and stage of each patient was classified according to the clas-

TABLE 1. Patients’ profiles and tumor characteristics: clinical staging according to the UICC criteria of 1997

Characteristics n %

Sex Male 65 88 Female 9 12Location 　Right 34 46 Left 29 39 Center 11 15Histological differentiation Well 20 27 Moderate 35 47 Poor 13 18 Unknown 6 8Subsite PS 50 68 PC 14 19 PW 10 13Stage (UICC1997) I 3 4 II 10 12 III 19 12 IVA 35 64 IVB 5 5 IVC 2 3T classification T1 9 11 T2 28 39 T3 29 28 T4 8 22N classification N0 21 28 N1 15 10 N2a 5 7 N2b 20 32 N2c 8 18 N3 5 5


regional lymph node metastasis. N1 is single ipsilateral lymph node metastasis, < 3 cm in greatest dimension. N2a is single ipsilateral lymph node, > 3 cm but not > 6 cm. N2b is multiple ipsilateral lymph nodes metastasis, none > 6 cm. N2c is bilateral or contralateral lymph nodes, none > 6 cm. N3 is a lymph node > 6 cm.

Details of the patients’ characteristics are listed in Table 1. The patients consisted of 65 males and 9 fe-males, with ages ranging from 31 to 81 years and a mean age of 63 years. The primary site was located on the right side of the hypopharyx in 34 patients, on the left side in 29 patients and in the center in 11 patients. The primary subgroup was located in the pyriform sinus (PS) of the hypopharynx in 50 patients, in the postcricoid (PC) region in 14 patients and on the posterior pharyngeal wall (PW) in 10 patients. Specimens of all patients were confirmed as squamous cell carcinoma of the hypophar-ynx by histological examination. Of these, 20 were well-differentiated, 35 moderately differentiated, and 13 poor-ly differentiated; no definite confirmation of the grade of differentiation could be made in 6 patients. The numbers of patients classified as stage I, stage II, stage III, stage IVA, stage IVB and stage IVC were 3, 10, 19, 35, 5 and 2, respectively. Patients in the advanced stages, i.e., stage III and stage IV, constituted 82%. The T classification was T1 for 9 patients, T2 for 28, T3 for 29, and T4 for 8. The N classification was N0 for 21 patients, N1 for 15, N2a for 5, N2b for 20, N2c for 8 and N3 for 5.

Sixty-four patients underwent radical treatment, and 10 patients underwent palliative treatment or no treat-ment. Fifty patients underwent surgical resection of their primary tumors, 23 patients received radiation for their primary tumors, 52 patients underwent neck dissection. Patients with tumors evaluated worse than pN2 were treated by postoperative irradiation. Chemotherapy was used for laryngeal preservation or additional treatment of

advanced cancers. Details of the treatment are shown in Table 2.

We used the criteria of multiple primary cancer pro-posed by Warren and Gates (1932). 1) Each of tumors must present a definite picture of malignancy, 2) each must be distinct, and 3) the probability that one was a metastatic lesion from the other must be excluded. Multiple primary cancers were considered to be synchro-nous when found at the same time or within a six month period after diagnosis of hypopharyngeal cancer. Cancer found after six months was referred to as metachronous cancer (Gluckman and Crissman 1983). Multiple prima-ry cancers before incidence of hypopharyngeal cancer were evaluated based on anamneses and medical records. At initial treatment, except for locoregional evaluation of hypopharyngeal cancer, we routinely performed flexible gastroscopy, radiograph or CT of the chest, ultrasonogra-phy of the abdomen, and examination of occult blood in feces and urine. We performed colonoscopy, urological examination on demand. After treatment, follow-up vis-its were performed every 1-3 months. We routinely per-formed clinical examination of head and neck, including MRI or CT of head and neck, flexible nasopharyngolar-yngoscopy and radiograph of the chest. We also per-formed CT of the chest, flexible gastroscopy, and other examination on demand. When the patients died of mul-tiple primary cancers, we confirmed no recurrence of hy-popharyngeal cancer based on medical records including laboratory data, imaging, and physical examination. Survival time was measured from the initiation of treat-ment. The cause-specific survival was calculated based on the event of patient’s death of hypopharyngreal can-cer. We calculated locoregional control rate based on the event of the patient’s locoregional recurrence of hypo-pharyngeal cancer. Actual survival probabilities were calculated using the method of Kaplan-Meier, and com-

TABLE 2. Stage and treatment strategy of patients

Stage Number ofpatients

Primaryresection

Neckdissection Chemotherapy Radiation No treatment

I 3 3 2 3 1 0II 10 2 2 7 9 0III 19 17 17 10 10 0IVA 35 26 28 16 24 3IVB 5 0 1 5 5 0IVC 2 2 2 1 1 0Total 74 50 52 42 50 3


parisons of survival curves between all different sub-groups were performed using the log-rank test. Informed consents of the patients were taken before treatment, and this study was approved by the ethics committee of Miyagi Cancer Center.

RESULTS

The overall 5-year survival rate of all pa-tients was 38%, and the cause-specific survival rate was 48%. The overall 5-year survival rate and cause-specific survival rate of the patients who received radical treatment were 43% and 56%, respectively. The ten patients who received palliative treatment or no treatment died of cancer within 16 months. The overall survival rate at 5 years was 33% for patients with stage I cancer, 47% for those with stage II, 63% for those with stage III, 28% for those with stage IVA, and 0%

for those with stage IVB or IVC (Fig. 1). The survival rate of stage I patients was worse than expected. There were significant differences be-tween the survival rate of the patients evaluated as stage I and that of the patients evaluated as stage IVB. There were also significant differenc-es between the survival rate of the patients evalu-ated as II, III, or IVA and that of the patients eval-uated as IVB or IVC.

The 5-year survival rate by T classification was 22% for patients with T1 tumors, 44% for T2, 41% for T3, and 19% for T4 (Fig. 2A). The 5-year survival rate by N classification was 45% for patients with N0 tumors, 67% for patients with N1 tumors, 40% for patients with N2a tu-mors, 26% for patients with N2b tumors, 13% for patients with N2c tumors, and 0% for patients with N3 tumors (Fig. 2B). The survival rate was

Fig. 1. Survival curves of the patients by stage classification. There were significant differences between the survival rate of the patients evaluated as stage I and that of the patients evaluated as stage IVB (p = 0.03), and between that of the patients evaluated as II, III and that of the patients evaluated as IVB, IVC (p < 0.01). There were also significant differences between the survival rate of the pa-tients evaluated as stage IVA and that of the patients evaluated as IVC (p = 0.01), and between the patients evaluated as IVA and that of the patients evaluated as IVC (p < 0.01). All of the patients diagnosed as IVB and IVC died of cancer within 22 months.

　　 , stage I (n = 3) 5-year survival rate of 33%; , stage II (n = 10) 5-year survival rate of 47%; , stage III (n = 19) 5-year survival rate of 63%; , stage IVA (n = 35) 5-year survival rate of 28%; , stage IVB (n = 5) 5-year survival rate of 0%; , stage IVC (n = 2) 5-year survival rate of 0%.


Fig. 2. Survival curves of the patients by TN classification. A: Survival curves by T classification. There was no significant difference among these 4 groups.

　　 , T1 (n = 9) 5-year survival rate of 22%; , T2 (n = 28) 5-year survival rate of 44%; , T3 (n = 29) 5-year survival rate of 41%; , T4 (n = 8) 4-year survival rate of 19%.

　　B: Survival curves by N classification. The survival rate of the patients evaluated N0 and N1 was better than that of the patients evaluated as N2c and N3 (p < 0.01). Survival rate of the patients evaluated as N3 was worse than that of the patients evaluated as N2a and N2c (p = 0.02). The pa-tients with N3 tumors died of cancer within 22 months.

　　 , N0 (n = 21) 5-year survival rate of 45%; , N1 (n = 15) 5-year survival rate of 67%; , N2a (n = 5) 3-year survival rate of 40%; , N2b (n = 20) 5-year survival rate of 26%; , N2c (n = 8) 5-year survival rate of 13%; , N3 (n = 5) 5-year survival rate of 0%.


significantly related to N classification but not re-lated to T classification.

In the 64 patients who received radical treat-ment, disease recurred after the initial treatment in 33 patients between 3 and 70 months with a

mean onset time of 14 months (Fig. 3A). There was local recurrence in 8 patients. Of these, 6 pa-tients had only local recurrence, one suffered from both local and distant metastasis, and one experi-enced local recurrence, regional lymph node re-

Fig. 3. The patterns of recurrence and cause of death. A: The pattern and frequency of first recurrence of the patients who received radical treatment. Distant metastasis was most frequent. Local recur-rence = 8/64 (13%). Regional recurrence = 12/64 (19%). Distant metastasis = 18/64 (28%).

　　B: The pattern of causes of deaths of all patients. ( ): palliative or no treatment. The frequency of death due to distant metastasis, the most frequent cause of death, was 56% (25/45). Death due to local lesion = 11/74 (15%). Death due to regional lesion = 15/74 (20%). Death due to distant me-tastasis = 25/74 (34%).


currence and distant metastasis. Regional lymph node recurrence occurred in 11 patients, alone in 9 patients and together with distant metastasis in 1. Among 18 patients with distant metastasis, 15 pa-tients showed no evidence for local and regional lymph node recurrence between 3 and 41 months with a mean onset time of 14 months (Fig. 3A).

Forty-five patients died between 1 and 98 months with a mean survival period of 21 months after initial treatment. Thirty-seven patients died of hypopharyngeal cancer. Six patients died of multiple primary cancers. One patient died of brain infarction and one other patient died of an unknown cause. The cause of the death of 11 pa-tients was local recurrence of the disease, as judged by their clinical history. Of these, 3 pa-tients died of local lesions alone, 5 died of local and regional lymph node lesions, 2 died of local lesions and distant metastasis, and 1 died of local, regional and distant metastasis. We also con-firmed that the cause of the death was regional node recurrence of the disease. Of these, 4 pa-tients died of regional lymph node lesions alone, and 5 died of regional and distant metastasis (Fig. 3B). Distant metastasis occurred in 25 patients, and 17 of them died of distant metastasis and one is still alive despite metastasis. The metastatic le-sions of these 25 patients were found in the lung (16 patients), the bone (2), the lung and bone (6), and the lung and liver (1).

Twenty-three out of 74 patients had multiple primary cancers (31%). Four patients had triple primary cancer lesions and 1 patient had quadru-ple primary cancer lesions. Table 3 shows clinical course and site distribution of multiple primary cancer lesions. The most frequent site of multiple primary cancers was the stomach. This was fol-lowed by the esophagus, larynx and colon in this order. Twelve out of 74 patients had multiple pri-mary cancers before incidence of hypopharyngeal cancer (16%). Nine out of 74 patients had syn-chronous multiple primary cancer (12%). Five out of 74 patients had metachrounous multiple primary cancers after the incidentce of hypopha-ryngeal cancer (7%). Cause of the death of six patients was confirmed to be primary cancers oth-er than hypopharyngeal cancer by physicians in

other department or other hospitals.We analyzed the survival rate and the locore-

gional control rate of the method of primary treat-ment. Fifty patients underwent primary resection and 21 patients underwent radiation for their pri-mary tumors. There were no significant differ-ences of the survival rate and locoregional control rate between these two groups. Results of treat-ment are shown in Table 4. Thirty-seven patients underwent total pharyngolaryngectomy with cer-vical esophagectomy (TPLE), 6 patients under-went total laryngectomy with partial pharyngecto-my (TL), and 7 patients underwent partial pharyngectomy (PP). The survival rate and lo-coregional control rate of the patients who re-ceived PP were significantly lower than those of the patients received TPLE.

Thirty-six patients received intravenous sys-temic chemotherapy, including conventional CDDP (cisplatin), 5FU-combined therapy, and weekly low-dose CDDP therapy. Six patients un-derwent intra-arterial CDDP chemotherapy aimed at laryngeal preservation. Thirty-two patients re-ceived no chemotherapy. There was no signifi-cant difference among these three groups.

Fifty-two patients out of 74 patients under-went neck dissection (ND); forty patients under-went ipsilateral ND alone and 12 patients were evaluated as N2c and underwent bilateral ND. Four of the patients who had undergone ipsilateral ND alone experienced contralateral regional recur-rence between 6 and 18 months with a mean peri-od of 12 months. These four patients were salvaged from hypopharyngeal cancer by contra-lateral ND, but 1 of them died of distant metasta-sis of gastric carcinoma 34 months after the initial treatment. Retropharyngeal node metastasis was found in 5 out of 74 patients (7%). All patients with retropharyngeal node metastasis died be-tween 3 and 13 months with a mean period of 12 months after the initial treatment.

On initial treatment, by histological exami-nation of dissected lymph nodes, we found 2 ipsi-lateral metastatic lymph nodes (4%) in the sub-mandibular region, 32 (62%) such nodes in the upper jugular region, 18 (35%) such nodes in the mid-jugular region, 13 (25%) such nodes in the


lower jugular region, 6 (12%) such nodes in the paratracheal region, and one (2%) such node in the supraclavicular region. Metastatic lymph nodes were mainly located at levels II, III and IV. In two patients, however, metastatic nodes were found at the medial inferior site of the subman-dibular gland. Contralateral lymph node metasta-sis was found in 10 patients histologically.

We analyzed the survival rate and the locore-gional control rate based on the pN classification (Table 5). The 5-year survival rate of tumors di-

agnosed as pN0 was significantly higher than those diagnosed as pN2c. The survival rate of the patients evaluated as pN0 was higher than that of the patients who had 3 or more metastatic lymph nodes. There was no significant difference in the locoregional control rate among these groups.

DISCUSSION

This is a retrospective mono-institutional re-view of all patients diagnosed with hypopharyn-geal cancer and admitted to Miyagi Cancer

TABLE 3. Clinical course and sites of multiple primary cancers

Patient No. Beforea Intervalb Synchronousc Intervalb Metachronousd Cause of death

1 Stomach Alive 2 Stomach Alive 3 Stomach Hypopharynx 4 Esophagus Hypopharynx 5 Kidney Kidney 6 Lung Hypopharynx 7 Stomach 28 Hypopharynx 8 Stomach 36 Stomach 9 Stomach 36 Hypopharynx10 Stomach 57 Hypopharynx11 Esophagus 60 Alive12 Esophagus 70 Hypopharynx13 Larynx 72 Alive14 Urinary bladder 24 Alive15 Thyroid 300 Hypopharynx16 8 Esophagus Esophagus17 21 Esophagus Alive18 21 Colon Colon19 Esophagus 17 Mesopharynx Hypopharynx20 Stomach 228 Unknown

Gingiva 7221 Stomach 29 Esophagus Esophagus22 Esophagus, Stomach Alive23 Larynx 96 12 Colon, Pancreas Pancreas

a Multiple primary cancers before incidence of hypopharyngeal cancer.b Interval means the term of each cancer incident (months).c Multiple primary cancers were considered to be synchronous when found at the same time as or within

a six month period after the diagnosis of hypopharyngeal cancer.d Multiple primary cancers found after six months was referred to as metachronous cancer (after).Patient No. 20 was a survivor of the atomic-bombing.


TABLE 4. Results of treatment

n 5-year survival rate(%)

5-year locoreginalcontrol rate (%)

Treatment of primary lesiona

Primary resection 50 41 73 Radiation 21 32 48Method of primary resection PP 7 14b 43c

TL 6 33 80 TLP 37 47b 79c

Chemotherapyd

Intravenous 36 37 64 Intraarterial 6 50 50 No chemotherapy 32 37 65

a Excluding 3 patients received no treatment. There was no significant difference between two groups.b Survival rate of the patients received PP was significantly worse than those of the patients received

TLP (p = 0.02).c Locoregional control rate of the patients who received PP was significantly worse than those of the

patients who received TLP (p = 0.01).d There was no significant difference among the three groups.

TABLE 5. Results of pN classification

n 5-year survival rate(%)

5-year locoregionalcontrol rate (%)

pN classificationa

pN0 10 70b 80 pN1 5 80 80 pN2a 5 40 62 pN2b 22 35 60 pN2c 10 15b 47Pathological number of metastatic cervical lymph nodesc

0 10 70d 80 1 10 60 80 2 7 43 50 ≧3 25 24d 65

a There was no significant difference among the locoregional control rates of pN classification.b Survival rate of the patients evaluated as pN0 was better than that of the patients evaluated as pN2c

(p = 0.03).c There was no significant difference among the 5-year locoregional control rates of the 4 groups.d Survival rate of the patients evaluated the pN0 was better than that of the patients who had 3 or more

metastatic lymph nodes (p = 0.04).


Center. The overall survival rate reported in the literature is approximately 10% - 50%, with poor-er results in advanced stages (Pingree et al. 1987; Ho et al. 1993; Spector et al. 1995; Wahlberg et al. 1998; Godballe et al. 2002; Barzan et al. 2002). The overall 5-year survival rate of all pa-tients in our study was 38%, and the cause-spe-cific survival rate was 48%. The overall 5-year survival rate and cause-specific survival rate of the patients who received radical treatment in-cluding TPLE, following reconstruction by free jejunal transfer were 43% and 56%, respectively. The main failure was distant metastasis indicating that a new strategy, including chemotherapy and surgery, against distant metastasis is necessary to improve the survival rates.

Reports in the literature on multiple primary cancer of the hypopharynx are relatively few. The incidence of multiple primary cancers of the hy-popharynx has been reported to be approximately 10% - 20% in Japan (Ogawa et al. 1999), and the estimated 5-year metachronous cancer incidence rate has been found to be 34.4% (Schwartz et al. 1994). In our study, 23 out of 74 patients had multiple primary cancers (31%). Six patients died of multiple primary cancers other than hypopha-ryngeal cancer. Nine out of 74 patients had syn-chronous multiple primary cancer (12%). Five out of 74 patients had metachrounous multiple primary cancers (7%). Although the incidence of multiple primary cancers without other previous cancer was relatively low at this time, it is in-creasing (Ogawa et al. 1999), and thus long-term follow-up is needed. Regular examination includ-ing gastroscopy is important after initial treat-ment.

Treatment of primary tumors, including sur-gery and radiation, is decided based on the pa-tient’s condition and after consultation with the patient. In our results, the survival rate and lo-coregional control rate of the patients who re-ceived surgery tended to be higher than those of the patients who received radiation, but there was no significant difference between the two groups. In our results, the survival rate of the patients with stage I or T1 tumors was worse than that of the patients in other groups, as shown by the fact that

the patients who received PP had a worse survival rate than those who were treated with other meth-ods of primary resection. In 7 patients who un-derwent PP, there was local recurrence in 2 cases, regional recurrence in 2 cases, and distant metas-tasis in 1 case. Although some studies have re-ported that larynx-sparing surgical procedures do not adversely affect survival (Eckel et al. 2001; Barzan et al. 2002), another study found that pa-tients so treated had a worse prognosis (Czaja et al. 1997). In the present study, results of PP for laryngeal preservation were unsatisfactory. Indications for PP and procedures including tran-soral resection or pharyngotomy are controversial (Zeitels et al. 1994; Steiner et al. 2001). When a patient needs to undergo partial resection of a pri-mary tumor, indication for PP must be carefully evaluated and additional therapies, including post-operative radiotherapy, are thought to be neces-sary.

The standard treatment of advanced hypo-pharyngeal cancer is surgery and postoperative radiotherapy (Vandenbrouck et al. 1977; Pingree et al. 1987; Frank et al. 1994; Axon et al. 1997; Hoffman et al. 1997; Eckel et al. 2001), while chemoradiotherapy aimed at larynx-preservation has recently been reported (Kraus et al. 1994; Clayman et al. 1995; Lefebvre et al. 1996; Zelefsky et al. 1996; Samant et al. 1999). Not all patients with hypopharyngeal cancer are treated by surgery for various reasons such as unresect-able primary cancer or lymph node metastasis, patient refusal, and severe cardiopulmonary disor-der (Eckel et al. 2001). In our study, although re-sults of primary resection were better than those of radiation, there was no significant difference. If treatment results of surgery or radiotherapy are not significantly different, we need to have multi-ple strategies to treat hypopharyngeal cancer and explain general results and complications of each treatment to the patients.

In our study chemotherapy had no influence on survival and locoregional control rates. Concurrent low-dose chemotherapy and intra-arterial chemotherapy were used for laryngeal preservation. It has been reported that concomi-tant or alternating chemotherapy in addition to ra-


diotherapy results in slightly significant benefits and is useful for larynx preservation. The low significance of the resulting benefits, however, in-dicates that this procedure must be further investi-gated (Pignon et al. 2000). The efficacy of intra-arterial chemotherapy should be further elucidated by follow up and accumulation of cases in the fu-ture. At our institution, intravenous conventional chemotherapy as neoadjuvant chemotherapy or adjuvant chemotherapy in patients who receive radical resection needs to be reconsidered.

Elective contralateral neck dissection is con-troversial (Nishijima et al. 1991; Anderson et al. 1996; Lassaletta et al. 2002). Four of our patients experienced contralateral regional recurrence, but they were salvaged by ND at the time of recur-rence. Although we presently consider elective contralateral neck dissection to be unnecessary, its advisability shoud be reconsidered based on re-sults of patient follow-up. It is well documented that regional lymph node metastasis of hypopha-ryngeal cancer is usually located at levels II, III and IV (Candela et al . 1990; Wenig and Applebaum 1991). In our results, regional metas-tasis was mainly located at these levels in the pa-tients who underwent initial neck dissection. Two patients who had a metastatic submandibular lymph node (level I), however, also experienced multiple lymph node metastases in other region including the retro-space of submandibular gland and the region near the hyoid bone. The histopa-thology of the one patient with metastasis to the submandibular lymph node was basaloid squa-mous cell carcinoma with a poor prognosis. Retropharyngeal node metastasis was found in 5 patients. All patients with retropharyngeal node metastasis died of cancer. Survival of the patients with retropharyngeal node metastasis was signifi-cantly worse than that of the patients with no ret-ropharyngeal node metastasis (data not shown).

Generally, the N classification, pN classifica-tion and number of pathological metastatic lymph nodes have been shown to be important prognos-tic factors (Ono et al. 1985; Barzan et al. 2002). In our results, the 5-year survival rate was signifi-cantly related to the pN classification and the number of pathological metastatic nodes.

In conclusion, the overall 5-year survival rate of our patients was 38%. The indication for and strategy of PP were decided carefully. Contralateral elective neck dissection is unneces-sary. Regular examination to detect second pri-mary malignancy is necessary. The main failure of hypopharyngeal cancer was distant metastasis. To improve general results, we should develop some strategy against hypopharyngeal cancer. New strategies including chemoprevention and surgery against distant metasistasis are necessary.

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