Is elective contralateral neck dissection necessary in 53 salvage total laryngectomy patients?

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Abstract

Historically, if the risk of occult nodal disease is >20%, elective neck dissection was advised for surgical management of squamous cell carcinoma (SCC).1, 2 A recent meta-analysis in the salvage laryngectomy setting (n = 1141) reported an occult nodal positivity rate (cN0pN+) of 11%,3 which was higher in advanced local supraglottic (24%) or transglottic (17%) disease. Therefore, in high-risk patients undergoing salvage laryngectomy, neck dissection is generally recommended. The cN0pN+ disease rate in the contralateral neck in salvage total laryngectomy remains unclear and studies have shown neck dissection does not improve locoregional control or overall survivial.4-6 The primary aim of this study is to report the rate of nodal metastases in the contralateral neck for patients undergoing salvage laryngectomy and to identify predictors of occult neck disease. Data were collected with Caldicott guardian approval (ref 16111). The South East Scotland Research Ethics committee waived the need for formal ethical approval due to the retrospective nature of data collection. The methods used for this review of a prospectively maintained database undergoing salvage laryngectomy have previously been outlined in PA Asimakopoulos et al, 2019.7 Details for all patients managed between 1 January 2008 and 31 December 2018 were included. In our analysis, patients were identified as having either lateral, midline or bilateral disease based on the macroscopic pathology report. To analyse the presence of contralateral disease in this study, contralateral disease was defined as: nodal disease contralateral to the primary site. Patients were considered to have no evidence of contralateral disease if either a pathological specimen was negative (pN0), or no neck dissection was done, and there was no evidence of disease in the lateral neck with a minimum of 36 months follow-up. Clinical and pathological variables were investigated with non-parametric tests (Fisher's exact test or X2 for continuous variables). A two-tailed P value of .05) P = .0002 (P .05) P = .0114 (P < .05)* (excluding no neck dissection) Overall, 12 (23%) patients died of disease-specific causes; 10 of which were due to recurrent disease and 2 were due to fistula complications post-operatively. Four (7.5%) patients had local recurrence, at a median of 35 months (4-44 months). This occurred in the midline for all patients. Four (7.5%) patients had regional recurrence in the operated neck, of which 2 were contralateral to the primary disease. This was based on pathological and radiological reports and occurred at a median of 21 months post-operative (range 5-26 months). Two (4%) patients developed distant metastasis, one at 4 months, the other at 6 months post-operatively. Of the 10 (19%) patients who died of recurrence, 9 (90%) patients had bilateral neck dissection and one (10%) patient who had no neck dissection died of local recurrence at 8 months post-operatively. No patient who had less than bilateral neck dissection developed recurrent regional disease in the undissected neck during a minimum follow-up. Of the 10 patients who had disease recurrence, 7 (70%) had selective neck dissection, 2 (20%) patients had modified radical neck dissection and 1 (10%) patient had no neck dissection. They all died of locoregional recurrence on the ipsilateral side. No patient received post-operative radiotherapy or chemoradiotherapy. Of the 53 salvage laryngectomy cohort, 26 patients died during follow-up. The 5-year overall survival (OS) and disease-specific survival (DSS) were 49% and 71%, respectively (Figure 1). The overall rate of nodal disease was 28%. In the cN0 setting, the occult rate of nodal disease was 9.4% (Table 2). When considered on a lateralised basis, there was an occult ipsilateral nodal disease of 21% and a contralateral rate of 2% (Table 2). In summary, of the 35 patients with lateralised primary disease, and nodal staging less than cN2C, 0% of patients had contralateral nodal involvement. Only 1 patient was cN + ve (cN2b), who presented with a recurrent midline tumour of the supraglottis, underwent bilateral neck dissections and was found to be pN2c. This patient went on to have a local recurrence and died 6 months post-operatively (Table 3). Over an 11-year period, 59 patients underwent salvage laryngectomy. On analysis, occult nodal metastasis was found on pathological staging in 9.4% of patients suspected of negative neck disease (cN0). Disease in the contralateral nodal neck was found in only one patient (2%). This occurred in a patient with a midline supraglottic tumour of size T3 with ipsilateral positive nodes found in levels 2 and 3, which correlates with multiple high-risk indicators of contralateral involvement. Overall, in the cN0 setting 0/46 (0%) and in the c N1-2b setting 1/8 (13%), harboured occult contralateral neck disease, respectively. This is a single-centre UK study with a large cohort of patients from a single tertiary referral centre, over a 11-year period which helps to limit variability in clinical practice and intra-operative factors that could influence the results. Data from clinical notes were matched with pathological and radiological reports to enhance its validity. The sample size is low, limiting the ability to draw robust conclusions. Eleven of our patients did not undergo a bilateral neck dissection. Therefore, we excluded all patients with less than 36 months follow-up from the analysis of occult nodal positivity. Elective neck dissection, in the salvage laryngectomy setting, remains controversial due to its potential for post-operative complications and the variability in rates of reported occult nodal metastasis. A recent meta-analysis for occult nodal metastasis in cN0 neck suggested an overall rate of 14% for all subsites of laryngeal cancer. Supraglottic primary disease site (24%) and advanced primary recurrent (cT3/T4) tumours (21%) were associated with the highest rates.8 A Brazilian group (n = 272) who analysed the issue of contralateral neck disease in the salvage laryngectomy setting also found low rates of occult disease (3.5%), with a higher risk associated with supraglottic primary sites, mainly involving level II and level III nodes.9 Gouzos et al looked at the 3-year outcomes for salvage laryngectomy patients with no clinical or radiological evidence of cervical nodal disease and found no significant difference in survival outcomes or post-operative complications based on extent of nodal surgery.10 This has been replicated in a meta-analysis also showing no significant difference of overall survival at 5 years in patients in the salvage laryngectomy setting against patients whose necks were observed.3 This is consistent with our own findings. The decision to offer salvage laryngectomy is complex and based on the patient as well as tumour-related factors. Occult nodal disease on either side of the neck is rare, with the 20% cut off rate level accepted for elective neck dissection in the primary setting. In patients considered suitable for surgery, rates of occult contralateral nodal disease are low, in the <cN2b setting. Patients with a supraglottic recurrence, advanced primary disease or evidence of high volume ipsilateral nodal disease are at higher risk of contralateral cN0pN+ disease. Disease management teams must weigh up the low rates of occult disease with the potential for increased complications related to more extensive surgical dissection against the fact that untreated disease may later present without a curative surgical option. Our results suggest that for the vast majority of patients who present for salvage laryngectomy, elective contralateral neck dissection is not required. There are no conflicts of interest to report in this study by the authors. The data that support the findings of this study are available from the corresponding author upon reasonable request.

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