Discussion

In modern head and neck surgery, low treatment-related morbidity and good oncological outcomes are the main goals.^{Reference Golusiński and Golusińska-Kardach20} In this regard, surgical morbidity, and acute and late-onset adverse effects of primary or adjuvant chemoradiotherapy, must be carefully considered when selecting the most adequate treatment. Comparison of the different treatment modalities is difficult because of the lack of randomised, controlled trials. Moreover, different stages, end points, observation periods and statistics make it even harder to compare the impact of one treatment relative to the others.

The present study attempted to compare the post-operative outcomes of the three main surgical approaches to oropharyngeal SCC. We designed it as a case-match study, with the aim of reducing bias related to tumour stage and tumour subsites, given that lateral wall or base of tongue tumours pose very different challenges for the surgeons. It is important to note that although efforts were made to match the groups closely, it was not possible to establish an exact match for age, sex and N-stage parameters (Tables 1 and 2). To our knowledge, no other previous study has directly compared the morbidity and post-operative outcome of the three surgical approaches.

Consistent with the literature, length of hospital stay was considerably longer for patients treated with transmandibular surgery, compared with lateral pharyngotomy and transoral laser microsurgery. This outcome reinforces the previous consideration regarding the higher complication rate and slower functional recovery characterising transmandibular surgery. In 2011, Diaz-Molina et al. reported a retrospective review of 155 patients surgically treated for oropharyngeal SCC. Thirty-nine per cent of the patients who underwent mandibulotomy developed significant complications such as salivary fistula, pneumonia and post-operative haemorrhage. The median duration of hospitalisation was 23 days.^{Reference Díaz-Molina, Rodrigo, Alvarez-Marcos, Llorente, Costales and Suárez6}

Duration of surgical procedure was also significantly longer for transmandibular surgery compared with lateral pharyngotomy and transoral laser microsurgery, as mandibulotomy and mandibular reconstruction are time-consuming, and almost all patients (81 per cent) required a flap reconstruction (compared with 14.3 per cent of the transoral laser microsurgery group and 4.8 per cent of the lateral pharyngotomy group). Rahmati et al. found similar rates of flap reconstruction in a cohort of patients affected by tonsil SCC, 48 per cent of whom were staged T_3–4 and treated via a mandibulotomy approach.^{Reference Rahmati, Dogan, Pyke, Palmer, Awad and Lee21}

Conversely, length of hospital stay in our transoral laser microsurgery cohort was longer in comparison with some previous reports. Williams et al. reported an average of 8 days of hospitalisation for patients treated transorally.^{Reference Williams, Kinshuck, Derbyshire, Upile, Tandon and Roland22} Holsinger et al., reported an average of 9 days to discharge.^{Reference Holsinger, McWhorter, Ménard, Garcia and Laccourreye23} By contrast, Lee et al. found similar results, with a mean of 14 days and 24.6 days for transoral laser microsurgery and transmandibular surgery, respectively.^{Reference Lee, Park, Byeon, Choi and Kim24}

The difference between our data and reports in the literature regarding length of hospital stay can be explained by the conservative attitude we decided to take towards transoral laser microsurgery patients, who are only discharged when swallowing rehabilitation is complete and the risk for post-operative haemorrhage is minimised. None of our transoral laser microsurgery patients had a nasogastric feeding tube or gastrostomy at the time of hospital discharge, and we recorded no post-operative mortality. In comparison, Williams et al.^{Reference Williams, Kinshuck, Derbyshire, Upile, Tandon and Roland22} reported that 4 per cent of patients had a gastrostomy at discharge, and Holsinger et al.^{Reference Holsinger, McWhorter, Ménard, Garcia and Laccourreye23} described a post-operative mortality rate of 2.6 per cent.

A nasogastric feeding tube was positioned in all patients treated with transmandibular surgery and lateral pharyngotomy, while it could be avoided in some cases of early-stage oropharyngeal SCC treated with transoral laser microsurgery. Time to oral feeding had a similar duration in the transoral laser microsurgery and lateral pharyngotomy approaches, while time to a functional swallowing recovery was considerably longer in patients undergoing transmandibular surgery. As stated, this result also affects length of hospital stay. The outcomes emerging from our study are in line with the literature.

In their prospective work on 57 cases of oropharyngeal SCC treated with transoral surgery or open surgery, Lee et al. found oral feeding restoration times of 1–22 days and 13–33 days, respectively.^{Reference Lee, Park, Byeon, Choi and Kim24} Ninety-three per cent of the patients operated via lateral pharyngotomy in the work by Laccourreye et al. needed nasogastric feeding tube insertion, with a median stay of 11 days.^{Reference Laccourreye, Benito, Menard, Garcia, Malinvaud and Holsinger25} Canis et al. reported a median duration for nasogastric tube feeding of 10 days in a cohort of 102 patients treated with transoral laser microsurgery for tonsil cancer.^{Reference Canis, Martin, Kron, Konstantinou, Ihler and Wolff26} In addition, Weiss et al. reported a median duration of 8.5 days (range, 1–131 days) in their study on 368 patients treated with transoral laser microsurgery.^{Reference Weiss, Ihler, Anczykowski, Bertlich, Kitz and Steiner27} In the latter study, 48 gastrostomy tubes had to be placed because of severe dysphagia and recurrent aspiration after adjuvant chemoradiotherapy. Chemoradiotherapy is a well-known detrimental factor for swallowing rehabilitation,^{Reference Gross, Townsend, Hong, Miller, Kallogjeri and Zenga28} and the low number of transoral laser microsurgery patients referred for adjuvant chemoradiotherapy may explain our good swallowing outcome.

The number of tracheostomies performed and time to decannulation were in line with the published literature,^{Reference Díaz-Molina, Rodrigo, Alvarez-Marcos, Llorente, Costales and Suárez6,Reference Bertolin, Ghirardo, Lionello, Giacomelli, Lucioni and Rizzotto14,Reference Laccourreye, Benito, Garcia, Menard, Bonfils and Holsinger17} with the transmandibular surgery group showing a doubled decannulation time compared with the transoral laser microsurgery and lateral pharyngotomy groups. We tend to perform more tracheostomies, with a slightly longer time to decannulation, for transoral resection, in comparison to those reported in some recent studies.^{Reference Holsinger, McWhorter, Ménard, Garcia and Laccourreye23,Reference Henstrom, Moore, Olsen, Kasperbauer and McGree29} Weiss et al., in the largest cohort of oropharyngeal cancer patients treated with transoral laser microsurgery, reported a 3.8 per cent rate of tracheostomies, most of which were placed when post-operative bleeding occurred, within 30 days after initial surgical treatment.^{Reference Weiss, Ihler, Anczykowski, Bertlich, Kitz and Steiner27} Post-operative haemorrhage is, in fact, the most common and life-threatening complication of transoral surgery. It can occur in 5.4–11 per cent of patients,^{Reference Weiss, Ihler, Anczykowski, Bertlich, Kitz and Steiner27,Reference Pollei, Hinni, Moore, Hayden, Olsen and Casler30} even 10–15 days after surgery, as the surgical defect usually heals by secondary intention. For that reason, we prefer to perform a primary tracheostomy, to prevent any massive bleeding that would lead to a high-risk and stressful emergency procedure.

In our experience, the highest percentage of close and positive resection margins at final histological examination was recorded in the lateral pharyngotomy group, and the lowest in the transoral laser microsurgery group. Many factors can explain these results, most of which are related to the transoral laser microsurgery technique itself. Transoral laser microsurgery is a step-by-step resection in which the surgeon can cut through the tumour to inspect the boundary between normal and diseased tissue under microscopic magnification in a more accurate way compared with conventional surgery.^{Reference Tirelli, Boscolo Nata, Gatto, Bussani, Spinato and Zacchigna31} Furthermore, the transoral laser microsurgery philosophy entails meticulous margin mapping, guided by frozen section,^{Reference Tirelli, Hinni, Fernández-Fernández, Bussani, Gatto and Bonini32} until complete (‘R0’ microscopically margin-negative) resection is attained. This can be achieved thanks to the low thermal damage of the carbon dioxide laser to tissue,^{Reference Tirelli, Gardenal, Gatto, Bonini, Tofanelli and Fernández-Fernández33} and the close co-operation between the surgeon and the pathologist, which facilitates reallocation of a positive margin for subsequent intra-operative re-resection.^{Reference Hinni, Zarka and Hoxworth34} Lastly, transoral pre- and intra-operative narrow-band imaging evaluation improves delimitation of the superficial margins.^{Reference Tirelli, Piovesana, Marcuzzo, Gatto, Biasotto and Bussani35–Reference Tirelli, Piovesana, Gatto, Tofanelli, Biasotto and Boscolo Nata37}

Another advantage of the transoral laser microsurgery approach is that subsequent surgical revision for positive margins can be easily performed with low patient discomfort. On the contrary, where the surgical defect is covered with a flap or direct suture, adjuvant chemoradiotherapy is the most common solution.^{Reference Zuydam, Rogers, Brown, Vaughan and Magennis38} Our data on adjuvant treatment confirm this statement. Nineteen per cent of transoral laser microsurgery patients were sent for adjuvant chemoradiotherapy, compared with 47.6 per cent and 57.1 per cent of the transmandibular surgery and lateral pharyngotomy patients, respectively. Only two patients in the transoral laser microsurgery group underwent surgical re-resection for positive margins, while all the others underwent a margin enlargement in the same session of the primary tumour resection, thus confirming the reliability of frozen section analysis in our departments.^{Reference Tirelli, Hinni, Fernández-Fernández, Bussani, Gatto and Bonini32} These observations cannot be divorced from a correct selection of patients for transoral resection.

The most important drawbacks of transoral surgery are related to the difficulty in exposing some tumours, the narrow working field, the need for long unwieldy instruments and the line-of-sight issue of the laser beam from the micromanipulator, which make transoral resection challenging. That is why transoral surgical approaches tend to be centralised to academic or at least larger cancer facilities with a sufficient volume of activity and an adequate learning curve.^{Reference Gal, Slezak, Kejner, Chen and Huang39} Furthermore, tumours going through the pharyngeal constrictor muscles, affecting the mandible or the prevertebral fascia, are not eligible for transoral surgery. In this sense, a major consideration in patient selection for transoral surgery is whether the transoral approach is likely to achieve complete resection, thus reducing the need for adjuvant chemoradiotherapy and its well-known negative impact on QoL.^{Reference Blanchard, Baujat, Holostenco, Bourredjem, Baey and Bourhis10,Reference Machtay, Moughan, Trotti, Garden, Weber and Cooper40}

If these conditions cannot be met, then other treatment modalities, including open techniques, must be considered.^{Reference Golusiński and Golusińska-Kardach20} In this context, lateral pharyngotomy represents a valid and safe treatment option, as it ensures reductions in surgery time, length of hospital stay, time to oral feeding and time to decannulation, with far fewer complications than transmandibular surgery. Previous studies demonstrated excellent disease-free survival after lateral pharyngotomy, when coupled with adjuvant chemoradiotherapy, despite the number of positive margins.^{Reference Bertolin, Ghirardo, Lionello, Giacomelli, Lucioni and Rizzotto14} This trend was confirmed in the preliminary disease-free survival data of our study, even with the limitations of the small sample size and the still inadequate follow-up time. Furthermore, this technique can be combined with a transoral definition of superficial margins, with narrow-band imaging and transoral sampling of superficial margins for frozen section, without increasing the morbidity rate or impairing functional outcomes in terms of breathing, swallowing and speaking.^{Reference Laccourreye, Benito, Garcia, Menard, Bonfils and Holsinger17}

The main limitations of this study are its retrospective nature and the excessively limited sample size and follow-up period to draw adequate conclusions on survival. On the other hand, the case-matched study design was intended to eliminate strong confounding factors, such as T stage and tumour subsite, in order to gain efficiency in comparing the functional outcomes of the three surgical approaches.