Introduction
Current management strategies for laryngopharyngeal cancer include open surgery, transoral laser microsurgery and chemoradiotherapy. Outcomes of these treatments are comparable in terms of survival, but vary with respect to treatment-related morbidities and cost.Reference Phillips, Sader, Brown, Bullock, Wilke and Trites1–Reference Gregoire, Hamoir, Rosier, Counoy, Eeckhoudt and Neymark4 The local control rates for the treatment of glottic cancer in patients with primary T1 and T2 stage tumours have been reported to be as high as 92 per cent and 88 per cent with one treatment using transoral laser microsurgery or radiotherapy respectively.Reference Agrawal and Ha5, Reference Rigby and Taylor6 The advantages of performing transoral laser microsurgery over radiotherapy are: decreasing length of treatment and hospital stay, resulting in decreased cost;Reference Phillips, Sader, Brown, Bullock, Wilke and Trites1, Reference Rigby and Taylor6, Reference Rigby and Taylor7 and specific targeting of pathology, resulting in fewer side effects and improved surveillance due to a very short period of swelling and erythema.Reference Taylor and Rigby8
The positive oncological and functional outcomes that have been observed following transoral laser microsurgery in early glottic cancer cases (in patients with T1 and T2 stage tumours) suggest that this is an effective primary treatment.Reference Ambrosch9 However, it is less clear whether this is the best treatment option for the management of recurrent laryngopharyngeal cancers following radiotherapy failure. Open surgery has acceptable survival outcomes but is associated with a long hospital stay, functional outcome deficits, and morbidity associated with long-term tracheostomy and gastrostomy requirements.
This article aimed to review the outcomes of patients with recurrent laryngopharyngeal cancer who underwent surgical salvage with transoral laser microsurgery at our centre following radiotherapy failure.
Materials and methods
Patients
In our centre, patients who develop recurrence of laryngopharyngeal cancer following chemoradiotherapy are given the option of transoral laser microsurgery as a curative treatment. The criteria for offering curative transoral laser microsurgery include recurrent laryngeal tumours that are radiologically staged as T3 or less. Selected patients with recurrent oropharyngeal cancer are also offered salvage transoral laser microsurgery based on the lack of pericarotid involvement.
The study comprised patients for whom primary treatment for laryngeal and oropharyngeal cancer with radiotherapy or chemoradiotherapy failed, and who subsequently underwent transoral (CO2) laser microsurgery between January 2002 and January 2010. A total of 16 patients (12 males, 4 females), with a mean age of 65.2 years (range 49–82 years), were identified.
Patients with tumour–node–metastasis (TNM) staging of T1N0M0 or T2N0M0 glottic cancer received only radiation, while all other patients in this study received chemoradiation therapy. Data on these patients were prospectively collected from an electronic database. All patients for whom chemoradiotherapy failed were assessed using endoscopy and imaging techniques (computed tomography, magnetic resonance imaging and positron emission tomography) in order to determine the extent of disease, metastasis and staging. Cancer staging was based on the post-operative surgical pathology report in line with the 2002 American Joint Committee on Cancer TNM staging system.
Treatment
All operations were performed by the senior author (SMT) within the Division of Otolaryngology-Head and Neck Surgery at our institution. The surgical procedures were carried out using a Sharplan CO2 laser (Tel Aviv, Israel). Resection was performed using a CO2 laser coupled with an Acuspot micromanipulator (Sharplan, Tel Aviv, Israel) at a power setting of 2–6 watts, in a continuous super-pulse mode, with a variable spot size. A tumour splitting approach was used in all cases. All tonsil resections were taken down through the superior constrictor into the parapharyngeal fat pad.
Follow up
All patients were followed up in the head and neck oncology clinic at the Queen Elizabeth Health Science Centre, in Halifax, Canada. The standard protocol for follow up entails an initial appointment within the first month after surgery, followed by three-monthly visits for the first year, four-monthly visits for the second year, six-monthly visits up to five years and yearly thereafter. All patients received a full head and neck examination, and flexible nasopharyngoscopy on follow-up visits, in order to check for any signs of local or regional recurrence. Patients were also asked routine questions regarding functional morbidities associated with swallowing and speech, and responses were documented in charts.
Outcome measures
A descriptive analysis of outcomes was conducted. The end points analysed were: resumption of oral intake, complications, locoregional control (defined as a second recurrence occurring after the completion of the initial salvage surgery), recurrence-free survival and overall survival.
Results
A total of 16 patients were identified, of which 10 patients had recurrent laryngeal cancer, 4 had recurrent tongue base cancer and 2 had recurrent tonsillar cancer. All of the recurrent tumour cases included in the study were radiologically staged between T1N0M0 and T3N2bM0 (Table I). At the time of the initial salvage transoral laser microsurgery, three patients underwent unilateral neck dissection and one patient underwent bilateral neck dissection. Mean follow-up time was 30.6 months (standard deviation of 29.5). Three patients in the laryngeal cohort developed locoregional recurrence and three of the six patients that had recurrent oropharynx cancer developed locoregional recurrence.
Table I Patient data
*Indicates placement for greater than four months. Pt no = patient number; y = years; ELS = European Laryngological Society classification; temp = temporary; G tube = gastrostomy tube; trach = tracheostomy; FU = follow up; mth = months; F = female; rTNM = radiologically staged tumour–node–metastasis classifications; Y = yes; N = no; M = male; ca = carcinoma; mets = metastases; COPD = chronic obstructive pulmonary disease
Although the disease process for cancers of the aerodigestive track may be different, the overall survival and disease-free survival rates for all patients in this study, at an average of 29.8 months of follow up (median of 17.5 months), were 50 per cent and 68.8 per cent respectively. The respective survival and disease-free survival rates were 60 per cent and 80 per cent for laryngeal cancer, and 33.3 per cent and 50 per cent for oropharyngeal cancer. Overall, five patients died due to disease recurrence and three died of causes unrelated to aerodigestive cancer.
Two of the six patients who had locoregional recurrence after salvage transoral laser microsurgery were treated with subsequent open surgery. One of the patients underwent total laryngectomy, and left and central neck dissection with a forearm free flap. This patient was retreated with radiotherapy, which was successful. The other patient received a partial laryngectomy, and the patient suffered local and metastatic recurrence. For all other patients who had recurrence, palliation was the only appropriate treatment.
All patients had negative margins after the salvage surgery with the exception of 1 patient who underwent successful repeat salvage transoral laser microsurgery within 30 days. No patients died as a result of treatment and the average length of stay in hospital following transoral laser microsurgery was 6.9 days (range of 1–20 days). Unfortunately, one patient was lost to follow up six months post-operatively.
With regards to functional outcomes, seven patients had a temporary tracheostomy following salvage transoral laser microsurgery (five of these were for oropharyngeal surgery), all of which were removed before discharge. Temporary nasogastric feeding tubes were placed in eight patients (50 per cent of the cohort), with three nasogastric tubes and one percutaneous endoscopic gastrostomy tube remaining in place for more than four months. Excluding the four aforementioned patients who required long-term supplemental feeding, full oral diet was restarted by post-operative day three for the remaining patients. Three of the four patients who needed supplemental feeding eventually returned to a normal oral diet. The patient who did not resume an oral diet died of recurrence. Post-operative aspiration was observed in two patients. No patients experienced any significant post-operative bleeding.
Discussion
Traditionally, the therapy of choice for recurrent laryngeal cancer following radiation treatment failure has been total laryngectomy. Total laryngectomy, although effective, is associated with significant functional morbidities which preclude the use of this technique when conservative methods are deemed appropriate. Alternatives to total laryngectomy include transoral laser microsurgery and open partial laryngectomy. The local control and survival rates of the open partial laryngectomy salvage procedure have been reported as being (approximately) 80 per centReference Nibu, Kamata, Kawabata, Nakamizo, Nigauri and Hoki10, Reference Shah, Loree and Kowalski11 and 70–89 per cent respectively.Reference Shah, Loree and Kowalski11–Reference Paleri, Thomas, Basavaiah, Drinnan, Mehanna and Jones14 This procedure is a good option for lower stage disease, especially in centres without the experience and equipment for salvage transoral laser microsurgery.Reference Paleri, Thomas, Basavaiah, Drinnan, Mehanna and Jones14 Unfortunately, there is a high risk of serious post-operative complications associated with this procedure such as fistulisation, delayed decannulation and aspiration.Reference Steiner, Vogt, Ambrosch and Kron15
Transoral laser microsurgery is an alternative technique for salvage surgical treatment following chemoradiotherapy. A study by Roedel et al. investigated the outcomes of this technique for recurrent glottic cancer cases (carcinoma in situ (Tis) to T4a stage tumours) after radiotherapy. These authors found that the locoregional control rates at 3 and 5 years following the first transoral laser microsurgery procedure were 46.1 per cent and 38.8 per cent respectively, with overall survival rates of 67.5 per cent and 53.3 per cent.Reference Roedel, Matthias, Wolff and Christiansen16 In comparison, Steiner et al. reported a 71 per cent locoregional control rate (for tumours radiologically staged between T1 and T4) in those who had undergone 1–4 transoral laser microsurgery procedures.Reference Steiner, Vogt, Ambrosch and Kron15 These authors reported 3 and 5 year survival rates of 74 per cent and 53 per cent respectively. Ansarin et al. found that 35 per cent of patients developed recurrence at 44 months (median), with a 5-year actuarial survival rate of 86 per cent for Tis, T1 or T2 radiologically staged cancers.Reference Ansarin, Planicka, Rotundo, Santoro, Zurlo and Maffini17 More recently, a meta-analysis has shown that at 24 months, single salvage transoral laser microsurgery procedures for laryngeal cancer resulted in a local control rate of 58.2 per cent.Reference Ramakrishnan, Drinnan, Kwong, Grant, Mehanna and Jones18
Only a few studies have investigated the outcomes of salvage transoral laser microsurgery for oropharyngeal cancers. Recent evidence showed a 75 per cent local control rate at 2 years, with survival rates of 68 per cent and 46 per cent at 2 and 5 years respectively.Reference Grant, Salassa, Hinni, Pearson and Perry19 Compared with other salvage treatments, transoral laser microsurgery survival rates are acceptable, and the risk of complication is much lower.Reference Levendag, Meeuwis and Visser20–Reference Kasler, Fodor, Oberna, Major, Polgar and Takacsi-Nagy23 In our study, two of the four patients who underwent tongue base salvage transoral laser microsurgery suffered recurrence and died, both of whom had stage T3 cancer. Unfortunately, if the initial salvage surgery for recurrent tongue base cancer is not successful, the options for a second salvage treatment are limited; however, the possibility of open surgery with free flap reconstruction may still exist.
Salvage transoral laser microsurgery is not possible for every patient. Some patients who have undergone radiotherapy develop distorted anatomy, scarring and severe trismus, which makes an endoscopic approach impossible.Reference Quer, Leon, Orus, Venegas, Lopez and Burgues24 Other contraindications to performing salvage transoral laser microsurgery include fixation of both vocal folds, involvement of both arytenoid cartilages, or extensive infiltration of the thyroid, cricoid cartilage and soft tissue of the neck.Reference Steiner, Vogt, Ambrosch and Kron15 It is also important to bear in mind (before considering a conservative approach) that the histological analysis of recurrent tumours shows different growth patterns compared with primary tumours; recurrent tumours can have submucosal invasion and microscopic tumour foci that can be understaged by endoscopy and imaging.Reference Zbaren, Nuyens, Curschmann and Stauffer25 The risk of understaging advanced tumours should be considered when planning salvage surgical treatment. Moreover, surgeon experience becomes increasingly important when performing salvage surgery on previously irradiated tissues, and it is our belief that this is a significant contributing factor in the success of transoral laser microsurgery, particularly in a salvage situation.
• Salvage treatments for upper aerodigestive cancer following chemoradiation failure include open surgery and transoral laser microsurgery
• Success rates for salvage surgery vary considerably
• Salvage transoral laser microsurgery is associated with less morbidity than total laryngectomy
• This treatment should be offered to select patients following chemoradiation failure
Transoral laser microsurgery salvage procedures offer a number of advantages over open surgery, such as a decreased risk of fistula formation,Reference Quer, Leon, Orus, Venegas, Lopez and Burgues24, Reference Roedel, Matthias, Wolff, Schindler, Aydin and Christiansen26 and preserved voice and swallowing function. Although a number of patients in this study had tracheostomies at the time of surgery, all were decannulated before discharge. At our centre, it is now rare for tracheostomy to be performed for salvage transoral laser microsurgery; this has decreased the risk of functional complications. In addition, repeat salvage surgery is less complicated, as tissue is better preserved compared with a free flap reconstruction. Roedel et al. argue that transoral laser microsurgery is a less invasive treatment than open surgical procedures, and it offers a method of tumour resection that is comparable to open surgery.Reference Roedel, Matthias, Wolff and Christiansen16 Adjunctive treatments such as a neck dissection are not contraindicated, because poor wound healing and associated complications are less of a concern.Reference Yiotakis, Stavroulaki, Nikolopoulos, Manolopoulos, Kandiloros and Ferekidis27 Finally, salvage transoral laser microsurgery is less expensive than open surgery, it results in shorter hospital stays, and it decreases the need for tracheostomy and the associated comorbidities.Reference Bradley, Ferlito, Suarez, Werner, Genden and Shaha28
Salvage surgery following radiotherapy for aerodigestive cancers can be performed using various methods, each of which has its own benefits and morbidities. A major advantage of salvage transoral laser microsurgery is tissue preservation and the option to carry out more invasive surgery if there is persistent disease. In this small prospective study, the use of salvage transoral laser microsurgery achieved acceptable oncological outcomes, and was associated with less morbidity and better function compared with open surgery.
