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Journal Information
Vol. 68. Issue 6.
Pages 328-335 (November - December 2017)
Vol. 68. Issue 6.
Pages 328-335 (November - December 2017)
Original article
DOI: 10.1016/j.otoeng.2017.10.003
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Results of Total Laryngectomy as Treatment for Locally Advanced Hypopharyngeal Cancer
Resultados de la laringectomía total en carcinomas localmente avanzados de hipofaringe
Patricia García-Cabo Herreroa, Laura Fernández-Vañesa, Fernando López Álvareza,b,c, César Álvarez Marcosa,b,c, José Luis Llorentea,b,c, Juan Pablo Rodrigoa,b,c,
Corresponding author

Corresponding author.
a Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
b Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain
c Ciberonc, Spain
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Tables (2)
Table 1. Clinical Characteristics of the Patients.
Table 2. Histopathological Characteristics of the Tumours.
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Introduction and objectives

Total laryngectomy (TL), with eventual postoperative radiotherapy, has proven to be effective in treating cases of locally advanced hypopharyngeal cancer. The aim of this study was to analyse the oncological outcomes of this procedure in patients with hypopharyngeal cancer classified T3 and T4.


We studied 59 patients (33 T3 and 26 T4a) with primary squamous cell carcinoma of the hypopharynx treated with TL from 1998 to 2012.


Mean age was 61 years with a male predominance (96.6%). All the patients were smokers and 96% consumed alcohol. Unilateral selective neck dissection (ND) was performed in 12 patients, unilateral radical ND in 11 patients, bilateral selective ND in 20 patients and radical ND plus selective ND in 14 patients. Sixty-six percentage of the patients received postoperative radiotherapy. Lymph node metastases occurred in 81% of the patients and extranodal invasion in 56% of them. Twenty-nine percentage of the patients had loco-regional recurrence, 17% developed distant metastases, and 25% a second primary tumour. The 5-year disease-specific survival was 46%.


TL extended to pharynx (with eventual postoperative radiotherapy) offers good oncological results in terms of loco-regional control and survival in locally advanced hypopharyngeal cancer, so organ preservation protocols should achieve similar oncological results to those shown by TL.

Hypopharyngeal cancer
Total laryngectomy
Organ preservation
Introducción y objetivos

La laringectomía total (LT), más eventual radioterapia, ha demostrado ser un tratamiento eficaz en los casos de cáncer de hipofaringe localmente avanzado. El objetivo de este trabajo es analizar los resultados oncológicos de este procedimiento en pacientes con cáncer de hipofaringe T3 y T4.


Se incluyeron 59 pacientes (33 pacientes con estadio T3 y 26 con estadio T4a) con carcinoma epidermoide primario de hipofaringe tratados mediante LT entre los años 1998 y 2012.


La edad media fue de 61 años, con predominio de varones (96,6%). Todos los pacientes excepto uno eran fumadores y el 96% consumía alcohol. Se realizó vaciamiento cervical funcional unilateral en 12 pacientes, radical unilateral en 11 pacientes, funcional bilateral en 20 pacientes y funcional más radical en 14. El 66% de los pacientes recibieron radioterapia postoperatoria. Un 81% de los pacientes presentaba metástasis ganglionares y de estos un 56% presentaba invasión extracapsular. Un 29% de los pacientes presentaron recidiva locorregional, un 17% desarrollaron metástasis a distancia y un 25% un segundo tumour primario. La supervivencia específica fue del 46% a los 5 años.


La LT ampliada a faringe (con eventual radioterapia complementaria) ofrece buenos resultados oncológicos en términos de control locorregional de la enfermedad y supervivencia en el cáncer de hipofaringe localmente avanzado, de modo que los protocolos de preservación de órgano deben alcanzar resultados oncológicos similares a los demostrados por la LT.

Palabras clave:
Cáncer de hipofaringe
Laringectomía total
Preservación de órgano
Full Text

Hypopharyngeal cancers are the third most common malignant tumours of the head and neck. Despite diagnostic and therapeutic advances, the general prognosis continues to be poor. The few initial clinical symptoms result in late diagnoses at advanced stages, hence the poor prognosis. Like cancers of the head and neck in general the most important risk factors for hypopharyngeal tumours are smoking and excessive alcohol consumption. These patients frequently have serious associated comorbidities and low socio-economic level.1

It is not unusual to encounter multiple primary tumours. In fact, approximately 25% of patients present second primary tumours.2 More than 50% of hypopharyngeal tumour patients have clinically positive cervical lymph nodes at the time of presentation. And up to 17% present distant metastases when a diagnosis is made.3 Furthermore there is a relatively high incidence of late distant metastases (i.e., 2 or more years after primary treatment has been completed) associated with an advanced stage of the disease at time of diagnosis.

The treatment of hypopharyngeal cancer is controversial, in part due to its low incidence, and the inherent difficulty in undertaking appropriately driven and randomised clinical studies. Therefore it is difficult to define the ideal treatment for a specific stage or site of hypopharyngeal cancer. In general, both surgery and radiotherapy (RT) are the pillar for most curative efforts aimed at this cancer. In recent years chemotherapy was added to the treatment strategy for specific advanced cases. In the case of pyriform sinus cancer, the administration of neoadjuvant chemotherapy followed by RT can result in preserving the larynx without endangering survival.

The five-year survival rate presented in most studies for locally advanced tumours of the pyriform sinus is in the range of 30%–35%. The factors that principally influence the prognosis and outcome of the disease directly relate to the degree of tumour extension and especially to the extent of lymph node involvement. The prognosis also depends on the site: tumours of the posterior wall having the poorest prognosis, while the best results are obtained with tumours in the pyriform sinus.4

Surgery is not free from complications; postoperative infection (particularly pharyngocutaneous fistulas) is the most common. The incidence varies and most commonly ranges from 15% to 25%. There are many risk factors that have been described and associated with the onset of fistulas: smoking, alcohol, chronic liver disease, diabetes mellitus, malnutrition, radio/chemotherapy prior to intervention, presurgical tracheostomy, tumour stage and type of suture used, among others.5

The main objective of our paper was to analyse the outcomes in patients with advanced hypopharyngeal carcinoma treated with total laryngectomy, plus eventual postoperative RT, compared to the results of previous studies in the era of organ preservation. We set ourselves the secondary objectives of determining the specific and global survival of the disease achieved by surgical treatment, of determining and analysing the main risk factors and their influence on survival after the disease, and of determining and analysing the secondary complications after surgical treatment.

Material and Methods

We reviewed the surgical register of our hospital's ENT department between January 1998 and January 2012, gathering the data of 59 patients diagnosed with primary, locally advanced, hypopharyngeal cancer treated by total laryngectomy (TL), with complementary RT in cases where it was indicated. Patients with T1 and T2 stages, patients who required reconstruction with regional or free microvascular flaps due to spread of the disease, and patients requiring rescue surgery after the organ preservation protocol were excluded.

The indication for TL in the study period included patients in an appropriate medical condition to tolerate the treatment, with hypopharyngeal carcinomas classified as T3 and T4a, who were not candidates for organ preservation surgery. None of the patients had distant metastases at time of diagnosis. The diagnostic assessment included flexible nasofibrolarygnoscopy with biopsy and cervicothoracic computerised tomography in all cases. In the patients were it was not possible to take a biopsy in the outpatient clinic, a direct microlaryngoscopy was performed and a biopsy taken under general anaesthesia.

Selective neck dissection was performed on the cases with lymph node metastases and prophylactically (unilateral or bilateral depending on the risk of hidden metastases according to published studies) for the cases with no clinical metastases. One patient did not undergo neck dissection, 12 patients unilateral selective neck dissection (areas II–IV), 20 patients underwent bilateral selective neck dissection; 11 cases underwent radical ipsilateral neck dissection and 14 patients selective lateral and radical extirpation of the cervical lymph nodes. Only one patient underwent dissection of the central area (area VI). Complementary RT was given according to the pathological findings. In general, the patients staged as T4a and/or N2–N3 received RT.

The clinico-pathological and demographic data were obtained from the hospital medical records. Informed consent was obtained from all the patients and the study was approved by the hospital's clinical research ethics committee.

The variables analysed were age, sex, toxic habits, comorbidities (diabetes mellitus, chronic obstructive pulmonary disease, heart and liver disease), personal history of ENT and non ENT cancer, TNM staging, (according to the TNM staging of the International Union Against Cancer, 7th edition), histological grade, antibiotic prophylaxis, complications of treatment and follow-up, relapse, development of distant metastases and appearance of a second primary tumour.

IBM-SPSS version 22.0 was the statistical software used. The Chi-squared test was used for comparison between the qualitative variables. Survival was calculated using the Kaplan–Meier method, and the differences between survivals were calculated using the logarithmic ranges method. Minimum follow-up of the patients was 36 months or until their death. Cox's regression model was used for the multivariate analysis. All the tests were bivariate and the level of significance was set at P<.05.


Fifty nine patients were identified in the study period with hypopharyngeal carcinoma treated initially by TL. The clinical characteristics are shown in Table 1. The mean age was 61 years (range 44–84 years), with a clear male predominance (97%). A high percentage of the patients had a history of smoking (98%) and almost all the patients also had a history of alcohol consumption (97%); of whom 41% were moderate drinkers (from 50 to 100g/day) and 46% heavy drinkers (consumption >100g/day). Fifty-six patients presented some of the comorbidities mentioned (Table 1). Ten percent of the patients had a personal history of cancer, of whom 3 (5%) had presented head and neck cancer previously in another site: 2 patients had carcinoma of the tongue and another of the floor of the mouth.

Table 1.

Clinical Characteristics of the Patients.

Characteristic  No. of Cases (%) 
<55 years  19 (32) 
55–70 years  26 (44) 
>70 years  14 (24) 
Female  2 (3) 
Male  57 (97) 
No  1 (2) 
Yes  58 (98) 
No  2 (3) 
Light drinker  6 (10) 
Moderate drinker  24 (41) 
Heavy drinker  27 (46) 
Diabetes  8 (14) 
COPD  19 (32) 
Heart disease  18 (30) 
Liver disease  11 (19) 
Personal history of cancer
No  53 (90) 
ENT area  3 (5) 
Non ENT area  3 (5) 

With regard to the tumour characteristics (Table 2), the tumour was located in the pyriform sinus in all of the patients; there was a similar number of patients staged as T3 (56%) and T4a (44%). Eighty-one percent of the patients presented lymph node metastases after anatomopathological study, of which 12 patients were N1, 26 cases N2 and 10 N3. The predominant stage was IV (73%). Extracapsular invasion was observed in 26 (44%) of the patients with lymph node metastasis, 19 cases (32%) presented vascular invasion and 2 patients (3%) perineural invasion. In terms of histological grade, moderately differentiated epidermoid carcinoma (42%) and poorly differentiated epidermoid carcinoma (37%) predominated; 2 cases presented basaloid carcinoma histology. The surgical margins of the tumour were positive in only 5 patients (8.5%, and all of them received postoperative RT.

Table 2.

Histopathological Characteristics of the Tumours.

Characteristic  No. of Cases (%) 
pT classification
T3  33 (56) 
T4a  36 (44) 
pN classification
N0  11 (19) 
N1  12 (20) 
N2  26 (44) 
N3  10 (17) 
III  16 (27) 
IV  43 (73) 
Histological grade
Well differentiated  10 (17) 
Moderately differentiated  25 (43) 
Poorly differentiated  22 (37) 
Other (basaloid carcinoma)  2 (3) 

Of the 59 patients, 39 received postoperative RT (66%); 34 of the 43 stage IV patients (79%) and 5 patients of the 16 with stage III tumours (31%).

The most common postoperative complication was surgical wound infection, which occurred in 37 patients (63%): 31 cases (53%) had a pharyngocutaneous fistula, 3 patients (5%) a cervical abscess with purulent drainage, and 3 patients (5%) a cervical abscess and subsequent pharyngocutaneous fistula. Five patients (8.5%) presented postoperative haemorrhage. There were 3 deaths secondary to the surgical intervention, due to septic shock due to cervical infection.

Of the 31 patients with a pharyngocutaneous fistula, 27 cases (88%) were resolved with conservative treatment, and only 4 patients (13%) required surgical repair. All of the patients were able to tolerate an oral diet at the end of the treatment.

The mean postoperative hospital stay was 38 days (median of 31 days), with a range between 14 and 170 days. The duration of the mean stay depended on whether there was postoperative infection. The mean stay of the cases with no postoperative infection was 18 days, while it was 51 days for the cases with pharyngocutaneous fistula and 49 days for all the cases with infection (pharyngocutaneous fistula and cervical abscess).

During follow-up 17 patients (29%) had local and/or regional recurrence and 10 patients (17%) had distant metastases, of which 7 were lung, 2 were lung and liver metastases and one patient had inguinal metastases. Eight of the 17 patients with local and/or regional recurrences underwent rescue surgery.

Fifteen patients (25%) presented a second primary tumour; the most frequent location was the lung (8 patients), followed by the ENT area (2 patients with carcinoma of the tongue and one case of the tonsil), liver (one case), oesophagus (one case), bladder (one case) and breast (one case).

Twenty-eight patients (47.5%) died as a result of the tumour or its metastases and 13 (22%) due to unrelated causes; 11 patients (19%) remained alive with no locoregional recurrence or distant metastases at the time of the last follow-up. Disease-specific survival for the total series (Fig. 1) was 55% at 3 years and 46% at 5 years. Overall survival was 45% at 3 years and 36% at 5 years.

Figure 1.

Graph of disease-specific survival (A) and of overall survival (B) of the total series according to the Kaplan–Meier method.


Disease-specific survival at 5 years for stage III patients was 68% and 38% for patients with stage IV, although the differences were not statistically significant, probably because of the few stage III patients (P=.122; Fig. 2). Overall survival for stage II at 5 years was 62%, whereas for stage IV it was 29% (P=.071; Fig. 2).

Figure 2.

Specific survival (A) and overall survival (B) for the disease according to stage.


The variables associated with lower disease-specific survival in the univariate analysis were a tumour staged as T4a (P=.191), the presence of lymph node metastases staged as N2 and N3 (P=0.003), extracapsular invasion (P<.001) and postoperative infection (P=.015) (Fig. 3). In the multivariate study (Cox's regression model), which included the abovementioned variables, only extracapsular invasion (RR=5.48; 95%CI=2.45–12.28; P<.001) and surgical infection (RR=3.88; 95%CI=1.53–9.79; P=.004) were significantly associated with lower specific survival.

Figure 3.

Disease-specific survival graphs according to the Kaplan–Meier method according to T staging in (A), N staging in (B), the presence of extracapsular invasion (C) and postoperative infection (D).


A tumour staged as T4a (P=.029), lymph node metastases staged as N2 and N3 (P=.004) extracapsular invasion (P=.08) and postoperative infection (P=.001) (Fig. 4) were also associated with lower overall survival. In the multivariate study (Cox's regression model) which included the abovementioned variables, tumours staged as T4a (RR=1.88; 95%CI=1.002–2.53; P=.04), extracapsular invasion (RR=4.9; 95%CI=2.4–9.99; P<.001) and surgical infection (RR=4.9; 95%CI=2.17–11.28; P<.001) were significantly associated with lower overall survival.

Figure 4.

Overal survival graphs according to the Kaplan–Meier method according to T staging in (A), N staging in (B), the presence of extracapsular invasion (C), and surgical infection (D).


The most appropriate treatment for advanced non-metastatic T3–T4 hypopharyngeal tumours is controversial. There are no studies that show better results than those achieved with radical surgery (extended total laryngectomy) and eventual postoperative RT and therefore, organ preservation should always be assessed from a risk–benefit perspective. It is particularly important to stress that radical surgery followed by RT is still the best method of achieving locoregional control in cases of tumours affecting the cartilage or with deep infiltration.4

At the beginning of the 1980s platinum-based chemotherapy became an additional option and, in particular, the era of clinical trials of larynx preservation was launched. Induction chemotherapy (5FU/Cisplatin chemotherapy regimen) followed by RT in the event of a reduction in primary tumour size of at least 50%, was the first approach to preserving the larynx.6,7

The concept of organ preservation has often been misinterpreted or unclear. Organ preservation means, and only means, that a complete organ is maintained in place whether or not its function is maintained. However, organ-preserving treatment must be understood as treatment where the organ's function, not its anatomy, is maintained.8,9

One of the first clinical trials performed on the treatment of hypopharyngeal cancer was by the European Organisation for Research and Treatment of Cancer, who undertook a multicentre trial on patients with tumours of the hypopharynx and the lateral epilarynx, at the level of the pyriform sinus (78%) and aryepiglottic fold (22%), who were candidates for total laryngectomy and partial pharyngectomy. Two hundred and two patients were included (only 194 were candidates for treatment), and randomised to undergo radical surgery followed by RT (94 patients) or two or three cycles of cisplatin (100mg/m2) and fluorouracil (1000mg/m2/day) followed by RT (100 patients) in those achieving complete response of the primary, or total laryngopharyngectomy if a complete response of the primary tumour was not achieved or selective neck dissection if there was no clinical response at the level of the lymph nodes. Survival at 5 years was similar in both groups (35% in the radical surgery arm and 30% in the chemoradiotherapy arm [QRT]), and 58% of the chemotherapy group survivors kept a functional larynx.10,11,13–16

This trial was included in a specific meta-analysis, the Meta-Analysis of Chemotherapy on Head and Neck Cancer Group, with a total of 86 randomised clinical trials performed between 1965 and 2000. This meta-analysis divided the patients into four groups according to the location of the tumour: oral cavity, oropharynx, hypopharynx and larynx. The benefit of chemotherapy on overall survival for each location was studied; observing that in the hypopharyngeal tumour group the 5-year survival was 3.9% better in patients that had received concomitant chemotherapy.12

Non-randomised studies have been published, some specific to laryngeal cancers, others to hypopharyngeal cancers and others mixing both.17,18 Beauvillain et al.,13 compared the results of conservative treatment compared to radical surgery for resectable hypopharyngeal tumours. They established two groups, the first was treated with induction chemotherapy followed by radical surgery with postoperative RT and the second was treated with induction chemotherapy followed by RT. The authors found an overall survival of 37% in the first group compared to 19% in the second group treated with QRT. In terms of response to induction chemotherapy, they observed better statistically significant survival with a complete or partial response to induction chemotherapy in patients in the radical surgery group with a 40% survival compared to 20% survival in the QRT group. However, no statistically significant differences were observed in the patients who did not respond to chemotherapy, with 22% survival in the first group and 12.5% in the second.

Harris et al.,15 found greater survival in patients with hypopharyngeal tumours treated with radical surgery compared to QRT, although these results were not statistically significant.

Although QRT is the most popular option and acknowledged to be efficient in the larynx (at the expense of more toxic effects), no trial has clearly demonstrated it to be superior to neoadjuvant chemotherapy in hypopharyngeal carcinomas.12

The results of our study show better disease-specific survival and overall survival at 5 years (46% and 36% respectively) than those described in previous publications. Thus, in the study by Harris et al.,15 patients treated with total laryngectomy with RT or postoperative radiochemotherapy achieve a specific survival of 36% at stage III and 24% at stage IV at five years. We should bear in mind that this series predominantly included patients at stage III and patients with T1 and T2 tumours; in other words, they achieved a similar or poorer survival in patients with a better prognosis.

In terms of survival, these could be considered adequate results for cancers at advanced stages, however despite advances in diagnostic methods and treatment, the prognosis of advanced hypopharyngeal cancer remains poor. From all the accumulated experienced in organ preservation, we conclude that, at present, there are various options for treating moderately advanced cancers of the hypopharynx that are candidates for extended total laryngectomy or total laryngopharyngectomy: radical surgery alone, neoadjuvant chemotherapy, ART and the introduction of molecular therapies, but none have shown better results in terms of survival to surgery plus RT. We must stress that a multidisciplinary approach is essential in selecting the best possible treatment specific to each individual patient. Multidisciplinary discussion will also help to improve the design of future clinical trials.

The prognostic factors are the same as those traditionally described for these tumours: T staging, N staging, stage IV, extracapsular lymph node invasion and postoperative infection. The most important prognostic factor in other head and neck locations as with laryngeal carcinomas is the presence of lymph node metastases. However, in our study there were no differences in survival between patients classified as pN0 and those classified pN1, the prognosis was much poorer for those classified as pN2 or above.19 Extracapsular lymph node invasion was an additional poor prognosis factor among the patients with lymph node metastases, and was the main determinant of specific and overall survival.

In terms of the complications of TL (plus neck dissection), it can be considered a safe procedure. There were 3 deaths secondary to septic shock; however these were patients with associated comorbidities. The main complication found was pharyngocutaneous fistula. According to the results obtained, we observed that the incidence of fistula (57.6%) was above that described by other authors (37% in hypopharyngeal tumours), although the incidence of surgical repair (13%) is similar to that previously published.20,21

These data indicate that, despite technical advances and the use of prophylactic antibiotics, postoperative fistula is still a major problem for these patients, and is the main cause for prolonged hospital stay and postoperative morbidity.

In conclusion, TL extended to the pharynx (with eventual complementary RT) offers good oncological outcomes in terms of locoregional control of disease and survival for locally advanced hypopharyngeal cancer, and therefore organ preservation protocols should achieve similar oncological results to those demonstrated for laryngectomy for them to be considered a valid alternative.

Conflict of Interests

The authors have no conflict of interests to declare.

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Please cite this article as: García-Cabo Herrero P, Fernández-Vañes L, López Álvarez F, Álvarez Marcos C, Llorente JL, Rodrigo JP. Resultados de la laringectomía total en carcinomas localmente avanzados de hipofaringe. Acta Otorrinolaringol Esp. 2017;68:328–335.

Copyright © 2016. Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello
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