SYMPOSIUM: HEAD AND NECK
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|Year : 2012 | Volume
| Issue : 2 | Page : 236--244
Early stage squamous cell carcinoma of the pyriform sinus: A review of treatment options
Department of Head and Neck Cancer, University Clinic of Radiotherapy and Oncology, Skopje, Republic of Macedonia
Department of Head and Neck Cancer, University Clinic of Radiotherapy and Oncology, Skopje
Republic of Macedonia
The purpose of this review of the literature was to present treatment options for early stage pyriform sinus cancer. Squamous cell carcinoma of the pyriform sinus, as the most frequent cancer arising from the hypopharynx, is rarely diagnosed in its early stage. Based on evidence from retrospective studies, conservation surgery and definitive radiotherapy are considered the available treatment modalities for patients presenting with stage T1 and T2 pyriform sinus carcinomas without clinical evidence of neck lymph node metastases, offering similar results with respect to disease control and functional organ preservation. Also, the high risk of occult metastatic nodal disease even in the earliest stage of pyriform sinus cancer entails elective neck dissection or elective neck irradiation to be considered mandatory. However, for patients with early stage pyriform sinus cancer, no level 1 study exists in which conservation surgery is compared with radiotherapy alone for the evaluation of local control or survival. Randomized multicenter controlled trials evaluating efficacy of conservation surgery and definitive radiotherapy, and correctly interpreting functional outcome for each of the treatment procedures examined are necessary to obtain sufficient evidence to influence the decision in the choice of the most effective treatment for early pyriform sinus cancer.
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Krstevska V. Early stage squamous cell carcinoma of the pyriform sinus: A review of treatment options.Indian J Cancer 2012;49:236-244
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Krstevska V. Early stage squamous cell carcinoma of the pyriform sinus: A review of treatment options. Indian J Cancer [serial online] 2012 [cited 2020 Jan 28 ];49:236-244
Available from: http://www.indianjcancer.com/text.asp?2012/49/2/236/102920
The hypopharynx extends from the superior border of the epiglottis and the pharyngoepiglottic folds from the level of the hyoid bone above to the lower border of the cricoid cartilage bellow. It is divided into three primary anatomic subsites: the pyriform sinuses, the postcricoid area, and the posterior pharyngeal wall. Squamous cell carcinoma of the hypopharynx is a relatively rare neoplasm accounting for 5% of all head and neck cancers.  Hypopharyngeal cancer remains one of the most lethal malignancies of the upper aerodigestive tract, , with causes of death being locoregional recurrences, distant metastases, second primaries, and comorbidities. 
Squamous cell carcinoma of the pyriform sinus is a highly malignant disease with a generally poor prognosis, accounting for almost 70% of all hypopharyngeal cancers.  It arises from the mucosa of the anatomic subsite of the hypopharynx represented as analogous to an inverted pyramid situated lateral to the larynx, with the base located superiorly and the anterior, lateral, and medial walls narrowing inferiorly to form the apex with its tip extending slightly below the cricoid cartilage. The pyriform sinus, lying outside the glottis, is a silent area allowing tumors to grow for a substantial period of time before symptoms occur. , Thus, there is only a small percentage of patients presenting with early stage pyriform sinus carcinoma defined by the American Joint Committee of Cancer (AJCC) as a T1 or T2 tumor without nodal involvement or distant metastases (stage I and stage II). Early stage pyriform sinus cancers can produce a mild, nonspecific sore throat or vague discomfort on swallowing. According to Tsikoudas et al.  globus sensation can be the only complaint with normal clinical findings in patients with early stage pyriform sinus carcinoma. The majority of patients with pyriform sinus cancer present with a history of significant tobacco or alcohol use. ,
Pyriform sinus carcinoma may demonstrate submucosal spread medially, laterally, superiorly, or inferiorly. In the case of lateral extension, the tumor tends to infiltrate the thyroid cartilage, but cricoid cartilage and thyroid gland involvement is also possible.  Medial extension associated with invasion of the intrinsic laryngeal muscles may result in vocal cord fixation.  Superior tumor extension can involve the base of the tongue while inferior tumor extension can involve the thyroid gland. This submucosal tumor extension, frequently demonstrated in surgical specimens, can result in inaccuracy in the estimation of tumor volume and should be taken into consideration during the treatment being either surgery or radiotherapy.
Due to the rich lymphatic network as one of the characteristic features of the entire area of the hypopharynx including pyriform sinuses, the presence of occult nodal disease in high percentage of patients must be considered as a striking problem even for early primary tumors.  It has been shown that bilateral occult lymph node metastases in patients with clinically negative neck are most frequently associated with cancers of the pyriform sinus (59%), with most of the metastatic lymph nodes located in levels II, III, and IV. ,, Also, occult nodal disease in ipsilateral paratracheal lymph nodes has been reported in 20% of patients with tumors arising from pyriform sinus apex presenting with clinically negative neck. 
The goals of treatment for early squamous cell carcinoma of the pyriform sinus should be directed to achievement of the highest local and regional control rate while minimizing the functional damage and optimizing patients' quality of life. Conservation surgery or definitive radiotherapy, when properly selected and performed, are considered effective treatment modalities for patients presenting with stage T1 and T2 pyriform sinus carcinomas without clinical evidence of neck lymph node metastases.  Surgical resection of the tumor with an adequate margin or delivery of external radiotherapy produces good results for favorable T1 and T2 carcinoma of the pyriform sinus originating high in the sinus without extension to the apex, obtaining satisfactory rates of local control while optimizing functional outcome. ,, It is supposed that 30-50% of patients with early stage pyriform sinus cancer have lesions that are suitable for conservation surgery or radiotherapy alone.  Comparing the results of primary radiotherapy and of primary surgery in 65 patients with early squamous cell carcinoma of the pyriform sinus, Jones et al. revealed that there was no statistical difference found in the 5-year survival rate between the two treatment groups.
However, the choice between conservation surgical procedures and radiotherapy as a primary treatment modality for early pyriform sunus lesions has been addressed and remains controversial with the existing discrepancies among different authors in the choice of larynx conserving treatment.  The selection of patients for one of these two treatment approaches must be carefully accomplished. Because of the lack of randomized trials comparing conservation surgery and radiotherapy for T1-T2 pyriform sinus carcinoma in terms of local control and functional outcome, the decision for adoption of one of these two treatment modalities should incorporate a complex assessment of the extent and volume of tumor and expected response to treatment modalities, age of the patient, patient performance status, patient pulmonary function, patient preference and compliance, and the expertise of the surgical team to effectively realize conservation surgery or the ability to deliver an adequate radiotherapy.
Conservation surgical procedures that should be considered for the early lesions of the pyriform sinuses are represented by partial pharyngectomy or partial pharyngolaryngectomy. The choice of a conservation surgical technique for T1-T2 pyriform sinus carcinomas depends on the location and the precise spread of the tumor.  Complete wide surgical resection with wide margins is critical when surgery is employed as the primary therapy. In selected patients with T1 and T2 lesions of the upper part and those of the medial wall of the pyriform sinus, a supracricoid hemilaryngopharyngectomy as a functional procedure involving the supracricoid hemilarynx and medial aspect of the pyriform sinus as well as the ipsilateral arytenoid is advocated.  Following this surgical approach, phonation is enabled with the contralateral vocal cord and there is a high possibility for swallowing rehabilitation. In patients with T1 and T2 lesions of the lateral wall of the pyriform sinus, partial pharyngectomy through a lateral approach (partial lateral pharyngectomy) is indicated.  Conservation surgery as a curative resection should be directed toward the removal of the pyriform sinus carcinoma with an adequate margin in all three dimensions and the clearance of regional lymph nodes in the neck. The subsequent free flap reconstructions restoring the continuity of the upper aerodigestive tract permit retention of swallowing and speech and breathing functions of the larynx.  However, free flap for reconstruction of partial lateral pharyngectomy is not always necessary. Taking into account that reconstruction with free flap may compromise the patency of aerodigestive track, partial lateral pharyngectomy and primary closure could be considered one of the choices in lateral pharyngectomy approach.
The indications for conservation surgery in patients with early pyriform sinus carcinoma are represented by the absence of gross tumor involvement and impaired mobility of vocal cords and arytenoids, as well as by the absence of thyroid cartilage invasion and involvement of the apex of the pyriform sinus and postcricoid area. ,, Patient age and respiratory function are very important selection criteria because these tumors are difficult to be surgically treated without inducing significant morbidity like compromised voice and increased risk of aspiration that is considerably worse when hypopharyngeal resection is combined with partial laryngectomy. Accordingly, patients with tumors involving the pyriform apex, or postcricoid area, or those with resectable tumors but having poor pulmonary function should not be considered as candidates for partial pharyngolaryngectomy.  Zbaren and Egger,  who analyzed the patterns of spread of carcinoma of the pyriform sinus, concluded that conservation surgery could be possible for lesions confined to the lateral wall, tending to extend laterally beyond the thyroid ala and rarely infiltrating the intrinsic laryngeal muscles, while for tumors presenting with extensive laryngeal involvement with spread to the contralateral side, conservation surgery is considered an inadequate procedure.
The transoral laser endoscopic resection as a new conservation surgical approach is suitable for T1 and T2 exophytic, highly differentiated squamous cell carcinomas with a minor tendency for metastases originating in the upper half of the pyriform sinus without extension to the apex or to the postcricoid area.  This surgical procedure offers several advantages over open surgical approaches because it preserves the submandibular and/or retropharyngeal lymph nodes, reduces fistula and septic complications, and does not produce functional deficits regarding speech and swallowing. ,, The advantages of this conservation surgical approach have been confirmed with the analysis of long-term results obtained by transoral CO2 laser microsurgery for early hypopharyngeal lesions arising from pyriform sinus. ,
Hypopharyngectomy by transoral robotic surgery analyzed in terms of efficacy and feasibility has been also shown to be a safe technique for the treatment of early pyriform sinus carcinoma. 
Radiotherapy as a single treatment modality for early (T1-T2) pyriform sinus carcinoma represents an effective, noninvasive approach offering local control rates similar to those achieved with conservation surgery and allowing preservation of laryngeal function.  Radiotherapy has been proved to be an effective treatment in early pyriform sinus carcinoma with quite satisfactory results obtained in terms of local control. However, success is generally correlated with the volume of the tumor, and the best results are obtained with superficial and small-volume tumors. , El Badawi et al.,  reviewing patients with cancer of the pyriform sinus treated with radiotherapy, surgery, or surgery and postoperative radiotherapy, confirmed that definitive radiotherapy is a suitable treatment approach for superficial lesions without vocal cord mobility impairment. The rates of local control decrease in bulky T2 lesions, in those larger than 2.5 cm, and in those extending to the apex of the pyriform sinus. , Better results in terms of local control are observed in patients with favorable T2 lesions characterized by exophytic tumor, good airway, normal cord mobility, and uninvolved apex. 
Conventionally fractionated radiotherapy employing total doses of 60-70 Gy in 30-35 fractions over 6-7 weeks has remained a mainstay in the treatment of patients with T1-T2 pyriform sinus carcinomas for decades. Using radiotherapy alone in patients with early stage pyriform sinus tumors and a clinically negative neck, both the primary tumor and the neck are concomitantly treated, thereby obviating the need for neck dissections and their associated morbidity and, at the same time, obtaining a high probability for cure. Additionally, definitive radiotherapy could be effectively employed in patients who are not suitable for conservation surgery because of anatomic extension of the tumor in the pyriform sinus apex, in those who refuse surgery, or who are poor surgical candidates because of underlying medical conditions. , According to Allal  who analyzed the trends toward conservative treatment in the management of early stages of pyriform sinus, definitive radiotherapy, due to the less stringent patient selection required, has been shown as a more frequently utilized treatment modality.
Elective treatment of the neck in patients with early stage pyriform sinus carcinoma is indicated because of the high incidence of occult metastases in cervical lymph nodes. , Addressing the potential for spread of disease to the neck even for early primary tumors of the pyriform sinus, decision about neck management must be made in accordance with the treatment plan for the primary lesion. Thus, in cases when the primary tumor is to be treated with conservation surgery, the neck should be electively dissected, whereas in patients planned for definitive radiotherapy for the primary lesion, the neck should be electively irradiated. Both elective neck dissection and elective neck irradiation are considered to be equally and highly effective in managing subclinical neck disease, providing regional control of more than 90%. ,,
Neck lymph node dissection should be performed according to the definitions of the American Academy of Otolaryngology Head and Neck Surgery (AAOHNS).  The selective neck dissection procedure defined by preserving one or more of the nodal levels that are routinely removed in radical neck dissection and thereby producing less functional morbidity and esthetic defects should be considered as treatment of choice in the surgical management of patients with clinically and radiographically negative neck.  Selective neck dissection in clinically N0 patients removes the lymph node groups based on the patterns of metastases which are predictable relative to the location of pyriform sinus cancer. It represents the most accurate procedure to diagnose occult metastatic disease. Besides identifying subclinical nodal disease, elective neck dissection offers an opportunity to obtain prognostic information based on pathologic staging and to identify high-risk patients who would benefit from postoperative therapy. , Thus, following neck dissection, postoperative radiotherapy should be considered for those patients who have histopatologically proven metastatic lymph nodes in the neck, and postoperative concurrent chemoradiotherapy should be recommended in cases with revealed extracapsular extension of the nodal disease.  In patients with early pyriform sinus cancer and clinically negative neck, ipsilateral selective neck dissection for lateralized lesions or bilateral selective neck dissection for lesions approaching the midline of levels II, III, IV should be performed.
Patients with early stage pyriform sinus carcinoma and clinical N0 disease are eligible for elective irradiation of the neck up to a maximum dose of 50 Gy, encompassing bilateral lymph nodes in levels II, III, and IV. Elective treatment of level VI is indicated for patients with cancer located in the apex of the pyriform sinus. The determination of the target volume of elective radiotherapy of the neck should follow the consensus guidelines developed by the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group/Danish Head and Neck Cancer Group (EORTC/RTOG/DAHANCA). 
Studies Reporting Results of Conservation Surgery
Several studies analyzed the results obtained with partial surgery in patients with early pyriform sinus carcinoma. In a series of 22 carefully selected cases of early pyriform sinus carcinoma treated with partial pharyngolaryngectomy, Barton  found survival rate of 55% at 5 years. Iwai et al. have shown that following subtotal pharyngolaryngectomy, three out of seven patients with pyriform sinus carcinoma extending toward the larynx remained cured at the end of 5 years without remarkably affected verbal communication.
In the retrospective review of 169 patients with carcinoma of the pyriform sinus, Marks et al.  reported 5-year actuarial survival rate of 59% for 80 patients treated with partial pharyngolaryngectomy. The observed primary and/or nodal failure rate for this group of patients was 23%.
In the retrospective analysis of Ogura et al.,  85 out of 175 patients with pyriform sinus carcinoma were treated with partial pharyngolaryngectomy. The reported 3-year survival rate was 59% and voice preservation was obtained in 52% of the patients treated with conservation surgery.
The results of the retrospective study of 351 cases with squamous cell carcinoma of the pyriform sinus treated at the Institute Gustave-Roussy revealed that the reported rate of locoregional control was 89% in 18 patients with T1 and T2 cancers of the pyriform sinus treated with conservation surgery. 
Laccourreye et al. reported excellent results achieved by supracricoid hemilaryngopharyngectomy in 34 patients with early pyriform sinus carcinoma. The 5-year local control rate was 97%, and the 5-year cause-specific survival rate was 55.8%. There was also a very low 5-year actuarial local recurrence rate observed (3.4%).
In the non-randomized comparison of therapeutic modalities for patients with carcinoma of the pyriform sinus, Spector et al.  reported good results achieved in 207 patients treated with partial pharyngolaryngectomy with or without postoperative radiotherapy. The cure rates at 5 years ranged between 49% and 73%, depending on the location and the extent of the disease.
In the study of Chevalier et al. on patients with early lateral margin and pyriform sinus carcinoma treated with supraglottic hemilaryngectomy and postoperative radiotherapy, 12 patients had T1 and 19 patients had T2 pyriform sinus lesions. Authors reported survival rate at 5 years of 78% in the T1 group and 38% in the T2 group. The reported local recurrence rate was 2% and the overall neck recurrence rate was 15%.
Analyzing the results accomplished with supraglottic hemipharyngolaryngectomy in 14 patients with T1 and 73 patients with T2 pyriform sinus carcinoma, Makeieff et al.  reported 5-year actuarial survival rate of 83% for T1 and 50% for T2 tumors. The reported rates of locoregional recurrence and distant metastases development were 20%, and 28%, respectively.
The effectiveness of organ-preserving transoral laser microsurgery for the treatment of pyriform sinus carcinoma was analyzed in the retrospective study of Steiner et al. Transoral CO 2 laser surgery was realized in 129 patients, of whom only 33 patients had stage I and II pyriform sinus carcinoma. The achieved recurrence-free survival rate at 5 years in this group of patients was 95%, and the 5-year overall survival rate was 71%.
Studies Reporting Results of Definitive Radiotherapy
Several non-randomized controlled trials explored the role of definitive radiotherapy in the treatment of early pyriform sinus carcinoma.
Million and Cassisi  reported 100% local control achieved with irradiation of lesions originating from the anterior or medial aspect of the pyriform sinus. The lower rate of local control (63%) for those T1 lesions originating from the lateral aspect of the pyriform sinus was considered as a consequence of the involvement of the apex of the pyriform sinus and the high probability for early cartilaginous involvement. Local control for T2 lesions was 60%, and 2-year absolute survival for stages I and II was 83%.
In the series of 434 patients with cancer of the pyriform sinus reported by Bataini et al.,  the achieved local control rate at 2 years for 90 patients with T1 or T2 lesion treated with radiotherapy alone was 68%. Local control was achieved in only 36% for T1 and T2 tumors treated with up to 65 Gy, but improved to 65% among patients who received more than this dose.
In the study of Dubois et al. conducted to ascertain the optimal treatment for carcinoma of the pyriform sinus, radiotherapy alone was compared with radiotherapy combined with surgical resection. In the series of 363 patients with pyriform sinus carcinoma, 209 patients were treated with definitive radiotherapy and 154 patients were treated with surgery and postoperative radiotherapy. In the group treated with radiotherapy alone, there were 61 patients with T1-T2 lesions. Twenty-four of them were present without metastatic lymph nodes in the neck. In this subset of patients, local recurrence following radiotherapy was identified in 6 cases (25%). Early pyriform sinus cancers (T1-T2) were present in 54 patients treated with combined treatment approach with a conservation operation sparing at least part of the larynx. All of them had metastatic nodal disease in the neck. The actuarial survival rates at 5 years for patients with early pyriform sinus lesions and clinically negative neck treated with external irradiation alone were 60% for T1 and 47% for T2 tumors. The 5-year overall survival rate in patients with T1-T2 cancers treated with surgery and postoperative radiotherapy was 37%. Reporting the results of both the treatment strategies, authors concluded that regarding the possibility of local control achievement for patients with early stage (T1-T2) pyriform sinus carcinoma, radiotherapy was equally effective as combined with surgery.
In the study of Mendenhall et al.,  54 patients with squamous cell carcinoma of the pyriform sinus treated with radical radiotherapy at the University of Florida in a period of 20 years were reviewed. The authors reported good results achieved in 29 patients with T1 and T2 lesions. The local control rate was 89% for T1 and 75% for T2 lesions. The ultimate local control after salvage surgery was 89% and 90% for T1and T2 lesions, respectively. The determinate survival at 5 years for stages I and II was 100%.
Radiotherapy as an effective treatment in the early stages of pyriform sinus carcinomas has been also confirmed in the retrospective study of Krengli et al. Of 90 patients who underwent definitive radiotherapy, 7 had T1 and 16 had T2 lesions. Locoregional control was obtained in 86% of patients classified as stage T1 and in 56% of patients with primary tumors staged as T2 lesions.
The effectiveness of radiotherapy as an alternative to conservation surgery in the treatment of early pyriform sinus carcinoma was shown in a study conducted at the University of Florida  on 73 patients with T1 and T2 lesions of the pyriform sinus treated with radiotherapy alone or followed by neck dissection. The following at the university should be completely deleted. Of those 73 patients, only 18 (25%) had a clinically negative neck at diagnosis. Authors reported excellent 5-year local control rates and ultimate local control rates of 88% and 94% for stage T1, and 79% and 91% for stage T2 disease. The achieved control of the clinically negative neck in the subset of patients with the primary tumor continuously disease-free was 100%. The ultimate control above clavicles was 100% for stage I and stage II, and no patient with stage I or stage II disease died as a result of pyriform sinus cancer.
The role of definitive external beam radiotherapy in the treatment of stage I and II pyriform sinus cancer was also evaluated in the study of Van Mierlo.  The observed loco regional relapse-free survival and overall survival at 5 years for patients with stage I and II disease treated by radiotherapy alone was 60% and 40%, respectively.
The study of Pameijer et al. was conducted to determine the role of volumetric analysis with pretreatment computed tomography and the score of the tumor based on the involvement of specific anatomic sites within the larynx and hypopharynx in prediction of local control in patients with early stage pyriform sinus carcinoma treated with definitive radiotherapy. The authors reported significantly reduced 2-year local control rates if tumor volume was greater than 6.5 mol (25%), relative to tumors with volume under 6.5 mol (89%). Revealing that tumor volume appears to be an important factor that influences patient outcome, these authors considered that stratification of patients with early pyriform sinus carcinoma into favorable and unfavorable groups for achievement of local control with definitive radiotherapy could be effectively performed by evaluation of pretreatment computed tomography.
Amdur et al. reported an update of the University of Florida experience with 101 patients with stage T1-T2, N0-N3, M0 squamous cell carcinoma of the pyriform sinus treated with radiotherapy alone. Stage I was present in 7 and stage II in 18 patients. The 5-year local control rates after definitive radiotherapy for T1 and T2 lesions were 90% and 80%, respectively. Local control with larynx preservation at 5 years was 91% for T1 cancers and 77% for T2 lesions. The ultimate local control at 5 years for T1 and T2 disease was 95% and 91%, respectively. The 5-year rate for initial locoregional control above the clavicles was 100% for stage I and 87% for stage II disease. The ultimate locoregional control above the clavicles at 5 years for both stage I and stage II was 96%. Tumor extension to the apex of the pyriform sinus detected in 14% of the patients with stage T1 was shown to significantly reduce local control for T1 lesions. Five-year overall survival rates for stage I and stage II disease were 57% and 61%, respectively.
In the multi-institutional nonrandomized retrospective study performed by Nakamura et al.,  39 patients with stage I and 76 patients with stage II hypopharyngeal cancer were treated with definitive radiotherapy. Of those, 70% (80 patients) presented with carcinoma originating in the pyriform sinus (27 with stage I and 53 with stage II). The 5-year local control rates with laryngeal voice preservation for T1 and T2 lesions were 87% and 74%, respectively. The 5-year disease-specific survival rate was 96% for patients with T1 lesion and only 70% for patients with T2 lesion. The 5-year progression-free survival rate according to T stage was 68% for patients with stage T1 and 52% for patients with stage T2.
In the study conducted by Rabbani et al.,  123 patients with T1-T2 pyriform sinus squamous cell carcinoma were treated with radiotherapy with or without neck dissection. The observed 5-year local control and overall survival rates were 85% and 35%, respectively. The achieved overall local control rate with a functional larynx was 83%. The ultimate local control rates for T1 and T2 lesions were 96% and 94%, respectively. Results of this study also confirmed the significant negative influence of tumor volume greater than 6.5 ccm on local control.
For patients with early stage pyriform sinus cancer, no level 1 study exists in which conservation surgery is compared with radiotherapy for evaluation of local control and survival. Analyzing the results of treatment of carcinoma of the hypopharynx, Hinerman et al. concluded that conservation surgical techniques sparing portions of the larynx without diminishing rates of local control and survival could be excellent treatment options for early, favorable primary lesions of the pyriform sinus. According to Robson,  laser surgery is associated with fewer complications than open partial surgery, with a shorter time to return to normal swallowing. Yet, there is some concern existing about the satisfactory functional outcome in terms of voice preservation with the use of conservation surgery or endoscopic laser resection in patients with early stages of pyriform sinus cancer. , Another concern regarding surgery as the preferred treatment modality is connected with the possible presence of histologically proven high-risk factors for development of local/regional failure following conservation surgical procedure. The recommended postoperative radiotherapy in patients with close or positive margins of resection,  and the recommended postoperative concurrent chemoradiotherapy in patients with multiple risk factors, such as close or positive resection margins, lymphatic and vascular embolism, perineural infiltration, and cartilage invasion, , performed following conservation surgery, are inevitably associated with increased morbidity.
On the other side, radiotherapy as a single treatment modality has long been recognized as an effective therapy for early pyriform sinus cancer, offering superior results in terms of functional preservation. , Based on evidence from retrospective studies evaluating the role of definitive radiotherapy or conservation surgery in early stage disease, Lefebvre and Lartigau  emphasized that the impressive improvement in radiotherapy techniques unequivocally enabled the acceptance of radiotherapy as an indisputable alternative to surgery. Newer radiation techniques such as three-dimensional (3D) conformal radiotherapy and intensity-modulated radiation therapy (IMRT), improving the homogeneity of dose distribution and therefore allowing delivery of higher total doses in the tumor while minimizing the dose to and volume of the surrounding normal tissues irradiated, ,, are the options guided to improve outcome results obtained with conventional radiotherapy.  The need for elective irradiation of the lymph nodes in the neck when elective dissection had not been performed during the surgical procedure and the necessity for postoperative treatment (radiotherapy with or without concurrent chemotherapy) with its related morbidity following conservation surgery for patients with high risk for local/regional failure could be also considered as arguments supporting definitive radiotherapy as a treatment of choice for early pyriform sinus tumors.
Based on the results of studies exploring the role of altered fractionation regimens in head and neck cancer, or exclusively in hypopharyngeal cancer, and the significant improvement in the rates of local control for hypopharyngeal lesions of T2 or greater, and possibly also for T1 tumors reported by several authors, ,,,, it can be presumed that besides the lack of data regarding the subsites of primary hypopharyngeal lesions treated, there would also be an expected benefit in terms of increased rates of local control for patients with early stage pyriform sinus carcinomas by the use of altered fractionation as compared to conventionally fractionated radiotherapy.
Nevertheless, definitive radiotherapy as an organ preservation treatment strategy is associated with long-term swallowing issues including xerostomia, difficulty managing solid food, and difficulty eating in social situations.  According to Mendenhall,  the high rates of local control obtained with definitive radiotherapy for low-volume T1-T2 pyriform sinus carcinomas could be accompanied by radiation-induced severe long-term swallowing dysfunction requiring long-term enteral nutrition. High rate of complications including tissue breakdown, chronic fistulae, and hemorrhage has been also recognized in patients in whom total laryngectomy was performed as surgical salvage for the treatment of local recurrence following radiotherapy alone.  This fact emerges notably out of the need for adequate stratification of patients with early stage carcinoma of the pyriform sinus into high versus low risk for local failure after definitive radiotherapy. Accordingly, it is expected that an adequate stratification would enable the selection of patients with unfavorable tumors for conservation surgical procedure, thereby reducing the number of patients requiring salvage laryngectomy due to the development of local recurrence following definitive radiotherapy. 
On the basis of the data study from the literature on the treatment of early pyriform sinus carcinoma, the conclusion can be drawn that the relatively scarce incidence of hypopharyngeal carcinoma in the total number of head and cancers and, at the same time, the low incidence of T1-T2 lesions arising from the pyriform sinus have undoubtedly influenced the absence of prospective randomized trials comparing the efficacy of conservation surgery with that of radiotherapy alone in patients presenting with early stage pyrifom sinus cancers. Thus, at present, there is insufficient evidence to guide management decisions on the most effective treatment for early pyriform sinus cancer. Nevertheless, despite the lack of level I study, cancer registry database could be utilized to answer this issue with adequate control of bias, such as a propensity score. The performance of well-designed multicenter randomized controlled trials evaluating the efficacy of open partial surgery or endoscopic laser resection carried out by acknowledged experts, and definitive radiotherapy using 3D conformal radiotherapy or IMRT in conditions of adequate equipment in patients with T1 and low-volume favorable T2 lesions of the pyriform sinus must be considered a necessity for the future. However, it should be emphasized that the conclusion regarding the optimal treatment must be accompanied by the correct interpretation of the functional outcome driven from the quality of life data analysis for each of the treatment procedures examined.
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