Transoral Robotic Surgery

Abstract

Transoral robotic surgery (TORS) became a valuable new head and neck surgery approach from the past decade since its approval. TORS was initially conceived for oropharyngeal squamous cell carcinoma (OPSCC); now, the indications are gradually extrapolated into other subsites. There have been numerous studies comparing the outcomes following surgical and non-surgical treatment, especially for oropharyngeal cancers. TORS for laryngeal cancers is in its infancy, and only a few reports are describing it. Many report suggestive of better functional outcomes following TORS, but level 1 evidence is still lacking. With the further development of novel, flexible, miniaturized robots, it is highly likely to expand TORS indications further. This article provides an overview of TORS in head and neck cancers.

Background

Traditional open approaches to resect oropharyngeal and laryngeal tumors have been the standard. The location of these tumors precludes a transoral route of resection. The open approaches afford a broad exposure to the surgical field, allowing ease of resection with adequate oncologic surgical margins. However, these open approaches are often associated with long-term sequelae of poor functional outcomes such as swallowing and speech impairment, resulting in a more inferior quality of life for these patients. The transoral approach naturally becomes the preferred route for advancing surgical techniques and care of head and neck patients. Transoral laser microsurgery (TLM) was developed in the late 1970s by Strong and Jako [1], and more recently, transoral robotic surgery (TORS) became a valuable new approach in head and neck surgery. Robotic surgery is defined as using an electromechanical machine to enable surgeons to operate with more efficiency and precision.

In 2005, Neil Hockstein from the University of Pennsylvania first introduced the da Vinci system into the head and neck [2]. The most popular robotic system in head and neck surgery is the da Vinci Xi HD (Intuitive Surgical, Sunnyvale, CA), used since 2005 to perform transoral resections of head and neck tumors. Robotic surgery got its FDA approval in 2009 for its use in head and neck surgeries. The next generation of the robotic system (FLEX Robotic System) was designed and manufactured by Medrobotics Inc. (Raynham, MA). This highly articulated platform features an endoscope made up of multiple discrete linkages, capable of rotating independently and achieving a semi-rigid or flexible state by varying the tension on the cables running through the segments. With the gradual adoption of robots in clinical practice, newer innovations to develop novel surgical systems have emerged, both within intuitive surgical and other industries producing this field.

TORS overcame several limitations inherent to TLM by offering surgeons the freedom to perform precise surgical maneuvers with exceptional (3D) endoscopic visualization, easier en bloc resection, better optics, better flexibility of instruments, and better hemostasis and hand tremor filtration with improved range of motion. This article provides an overview of the utilization of TORS for head and neck cancers.

Oropharynx

Transoral robotic surgery (TORS) was initially conceived for oropharyngeal squamous cell carcinoma (OPSCC). Traditionally OPSCC was treated with open surgery because of its difficult access and complex anatomical location. This had a significant impact on speech and swallowing with approximately 30% morbidity. A paradigm shift in treatment from the traditional open approach to concurrent chemoradiotherapy (CTRT) achieved reasonable locoregional control and comparable survival outcomes with minimum morbidity [3]. Although the initial results are promising, the late effects of the radiation therapy were of major concern because it significantly impacted patients’ quality of life. There is a rising trend of HPV-positive oropharyngeal cancer, which response well with CTRT, but the terrible long-term effects affect survivorship, especially in young patients[4].

TORS is a fascinating new tool that is useful in the modern management of selected cases of OPSCC. TORS is poised to have a more significant role in the management of OPSCC as the technology and training become more widely available to surgeons.

The principle of TORS surgery is en bloc resection with a clear margin. No universal definition of what constitutes an inadequate resection margin exists yet [5]. The guidelines from the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and the European Oncology Institute (IEO) all define a close margin as 5 mm or less without any subsite distinction. Alicandri-Ciufelli et al., in their comprehensive review on surgical margins in the head and neck, reported that most studies use a margin distance of 5 mm or greater to define margin clearance [6]. Weinstein et al. represented a margin of 2 mm or less to be considered close, and those greater than 2 mm considered a free margin [7].

TORS radical tonsillectomy is one of the first procedures surgeons undertake in the early stages of their TORS practice. The first report of TORS radical tonsillectomy was published in 2007 by Weinstein et al. [8].

Oncological Outcomes

TORS Versus Radiation

TORS appear to yield similar oncologic outcomes and better functional outcomes than primary RT (Table 1). However, patient selection favoring TORS likely biases this comparison. TORS studies tended to have a smaller proportion of advanced tumors and neck disease compared with chemoradiation series.

Table 1.

Oncologic outcomes of surgery and radiotherapy in early T-stage oropharyngeal squamous cell carcinoma (systematic reviews)

Study	Year	Inclusion	HPV	Treatment	Overall survival	Locoregional control
De Almeida et al	2014	T1–2, any N	NR	TORS: 67% adjuvant therapy RT: 56% RT alone, 44%CRT	TORS: 2-year OS, 82–94% RT: 2-year OS,84–96%	TORS: 2-year LRC, 94% RT: 2 year LRC, 91–96%
Kelly et al	2014	T1–2, any N	NR	TORS: adjuvant therapy NR	TORS: OS, 95%	TORS: LRC, 96%
Morisod et al	2016	T1–2, N0	NR	TOS: adjuvant NR RT: addition of chemotherapy NR	TOS: 5-year DSS, 82–97% RT: 5-year DSS, 86–95%	TOS: 5-year LRC, 79–94% RT: 5-year LRC, 71–88%

TORS, trans oral robotic surgery; RT, radiotherapy; LRC, locoregional control; OS, overall survival; NR, not reported; TOS, transoral surgery

Yeh et al. found that TORS can achieve oncologic outcomes that compare favorably to primary RT with an improved toxicity profile. TORS-based therapy OS was reported to range from 81 to 100% and DFS from 85.7 to 96%[9]. Mahmoud et al. study showed TORS’s 3-year survival rate versus nonsurgically treated patients at 93% and 83%. HPV-positive disease displayed no significant difference in 3-year survival at 95% and 91% for the TORS versus primary radiotherapy. In the HPV-negative cohort, TORS was associated with superior survival at 84% and 66% [10]. White et al. reviewed 89 patients, including 65% with T3–T4 tumors or N2–N3 disease. A total of 92% of patients underwent surgery with TORS as first-line treatment for their OPSCC, and this cohort demonstrated 89.3% overall 2-year survival [11]. The systematic review by de Almeida reported a 2-year overall survival estimate ranged from 84 to 96% for IMRT and from 82 to 94% for TORS[12].

Some authors have focused on TORS in those with HPV-negative early-stage OPSCC. Dabas et al. reviewed 57 patients who showed locoregional control in 95.8% and overall survival in 93.8% at a mean follow-up of 29 months [13]. The ORATOR trial is a phase II randomized trial for early-stage OPSCC: radiotherapy vs. TORS; Arm 1, radiotherapy ± chemotherapy; and Arm 2, TORS and neck dissection ± adjuvant radiotherapy/chemoradiotherapy based on pathological findings. Preliminary findings of this trial suggest no difference in survival between the two groups with the improved functional outcome with radiation. At the time of compiling this paper, the results were yet to be published.

TORS Versus Conventional Open Surgery

In a prospective non-randomized study by Sei Young Lee and colleagues which looked into the oncologic outcomes and functional recovery of transoral robotic surgery (TORS) or conventional surgery via a transoral or mandibulotomy approach in patients with tonsillar cancer, they found that there was no significant difference in the survival rate of the TORS group (100%), and in the conventional surgery group (96.7%), a higher rate of margin negativity was observed in the TORS group, especially in cases in which the tumor extends inferiorly. [14]

Magnuson et al. reported that robotic-assisted surgery showed better functional outcomes and low morbidity for the salvage surgery of primary or recurrent oropharyngeal tumors compared to conventional open surgery [15]. Haughey et al. treated patients diagnosed with advanced stage oropharyngeal cancer with transoral laser microsurgery (TLM) and reported a 3-year overall survival rate of 86% and a disease-free survival rate of 82% [16].

Functional Outcomes

Ideally, we would have long-term validated and homogenous data for comparison with functional outcomes associated with treatment. Unfortunately, as Roets et al. [17] highlights, interpretation of validated functional outcomes is “hampered by multiple confounding factors, including the use of different QOL questionnaires, the small inclusion, and heterogeneous populations, short follow-up with a large dropout of patients at long-term follow-up” and lack of balance in stages across treatment types. The most critical time frame for worsening swallowing, xerostomia, and speech occurred 3 months following therapy. The main advantage of TORS is an overall trend demonstrating improved swallowing outcomes and very minimal tracheotomy rates. The results of TORS in combination with adjuvant treatment are tabulated in Table 2. Chen et al. reported that the only outcome that differed between the two groups at 12-months was swallowing, with 74% of transoral patients reporting being able to swallow “as well as ever” compared to 32% in the CRT group [18]. More et al. presented dysphagia scores before treatment (baseline) and at 3, 6, and 12 months following treatment for TORS ± adjuvant and CRT patients with stage-matched OPSCC supraglottic squamous cell carcinoma and found no significant difference before treatment or at 3 month [19].

Table 2.

Functional outcomes of surgery and radiotherapy in early T-stage oropharyngeal carcinoma

Study	Year	Surgical treatment	Non-surgical treatment	Gastrostomy tube rates	Functional outcomes
Genden et al	2011	TORS 47% adjuvant CRT 36% adjuvant RT alone 17% no adjuvant	CRT 42% ICT + CRT 59% CRT alone	12 months: –TORS 0%, CRT 4%	No significant differences at 12 months
More et al	2013	TORS 60% adjuvant CRT 40% adjuvant RT alone Cisplatin for CRT group	CRT	6 months: –TORS 0%, CRT 60% 12 months: –TORS 0%, CRT 5%	Dysphagia index score (MD Anderson) higher in TORS at 12 months
Ling et al	2016	TORS 40% adjuvant CRT 16% adjuvant RT alone 43% no adjuvant	CRT	NR	Quality of life — saliva and chewing domains higher in TORS group at 12 months
Sharma et al	2016	TORS 28% adjuvant CRT 62% adjuvant RT alone 10% no adjuvant	93% CRT, 7% RT alone	6 months: –TORS 3%, CRT/RT 25% 12 months: –TORS 3%, CRT/RT 11%	NR

TORS, transoral robotic surgery; RT, radiotherapy; CRT, chemoradiotherapy; ICT, induction chemotherapy

The tracheostomy dependency rates have also improved to 0.1–4.5% for IMRT and 0–3.5% for TORS-based therapy. When done for TORS, tracheostomy is temporary only for the perioperative period and was more common in patients with bilateral nodal disease, the base of tongue tumors, and larger primary tumors [20]. Sethia et al. published a prospective cohort of 111 patients with OPSCC undergoing TORS alone, TORS + RT, and TORS + CRT; they report that the speech subdomain (functional) scores for TORS alone were significantly higher than for adjuvant CRT at 3 months and for adjuvant RT at 6 months [21].

Unknown Primary

The incidence of metastatic cervical lymphadenopathy from an unknown primary is around 2–5% of head and neck squamous cell carcinomas. The emergence of the primary lesion arises in the oropharynx in most of the lesions of metastasis of unknown origin in the head and neck. The localization of the primary tumor in patients with cervical metastasis of unknown origin remains a challenging yet important goal. Primary tumor detection will reduce the potential morbidity from treatment and better oncological outcomes.

There is a shred of growing evidence for the role of TORS in primary tumor identification and subsequent management. Blind biopsies from the tonsil and tongue base are no longer indicated. NCCN guidelines do not make any specific recommendation on sidedness of tonsillectomy, and in which cases, a tongue base resection needs to be performed. Tonsillectomy is always superior to deep tonsil biopsies and increases the likelihood of finding the primary in tonsils by 30%. Traditional lingual tonsillectomy, also known as tongue base resection, is defined as resection of the base of the tongue from the midline of the tongue to the lateral pharyngeal wall and from the circumvallate papillae to vallecula.

The application of TORS in unknown primary reduces the delay in diagnosis and obviates the need for second surgery but carries a small risk of bleeding ranging from 2 to 4.9%, with a mean hospital stay of around 1.4 and 6.3 days [22]. A recently published systematic review and meta-analysis for identifying primary sites found that tongue base mucosectomy (TBM) by TORS/TLM identified the primary in 53% of the cases. In patients with negative physical examination, diagnostic imaging, and PETCT, TBM identified the primary in 64%. In patients who had negative CT/MRI imaging, negative PETCT, and negative EUA and tonsillectomy, TBM identified a tongue base primary in 78% of cases [23].

In the meta-analysis by Meccariello et al., the primary tumor detection and positive surgical margins rates were 70.8% and 19.4%. The primary tumor was mainly in the base of the tongue (64%) [24]. A systematic review by Terence Fu et al. highlights the incremental benefit of lingual tonsillectomy by TLM or TORS in the detection of occult primary head and neck SCC when comprehensive diagnostic work-up of clinical examination, cross-sectional imaging, PETCT, and panendoscopy + tonsillectomy + blind biopsies does not yield the primary tumor [25]. TLM alone has enhanced occult tumor detection rates following lingual tonsillectomy of 61–68% [26, 27] versus 51–100% [28, 29] for TORS lingual tonsillectomy. A recent review by Ofo et al. concluded that TORS lingual tonsillectomy or tongue base mucosectomy has significantly improved the detection rate for a small base of tongue SCC, where conventional diagnostic techniques have failed [30].

To summarize, TORS seems to be an effective surgical approach in detecting primary tumor sites and has a therapeutic role in head and neck unknown primary.

Larynx and Hypopharynx

Most TORS for laryngeal cancer has focused on supraglottic laryngectomy [31, 32]. A complete supraglottic laryngectomy involves removing the entire laryngeal anatomy above the ventricles with the preservation of at least one cricoarytenoid unit. A review by Dziegielewski et al. in 2015 looked at the feasibility and outcomes of TORS in the larynx and hypopharynx. They concluded that the appropriately selected patients undergoing TORS for supraglottic laryngectomy had a better functional result, although the study was not controlled or randomized [33]. The application of TORS for total laryngectomy is in its infancy, and there are only a few case reports which have described it [34, 35]. The oncological safety and functional outcomes are yet to be measured.

The main concern for the TORS in glottis is the reach. There have been only a handful of case reports for the utilization of TORS in early and advanced glottic cancers. As the technology improves and cameras become smaller and robotic arms become more flexible, the instrumentation might lower resections.

T1 and T2 hypopharyngeal cancers that are amenable for partial pharyngectomy via a transoral approach can be accessed with the TORS, and there are few cases (35,36) described. The subset analysis of the TORS trial that looked into the feasibility and safety of transoral robotic surgery for early hypopharyngeal cancer concluded that TORS, when used in early hypopharyngeal cancers with appropriate neck dissection, is a valid primary treatment option, especially in cases that did not require adjuvant treatment [36].

Thyroid

Thyroid surgery has evolved gradually from butchery to fine microsurgery over the last century. There has been a recent trend in minimal access, scarless surgeries, and natural orifice transluminal endoscopic surgery (NOTES).

TORS has been tried for thyroidectomies in specific centers by utilizing the sublabial approach. The first series was reported by Lee [37] in 2015. They used this approach to perform lobectomy in four patients, with only one patient having papillary microcarcinoma. Unfortunately, three out of four operated patients developed mental nerve paresthesia, mainly due to the subvestibular port placement. A modification to this lateral port placement was devised by Anuwong [38] and the team in 2017; they reported no mental nerve paresthesia.

This approach is still in its infancy and needs further refinement, standardization to be used as a widespread technique. The idea of scarless surgery may look incredibly attractive, but the surgeon must understand the risks associated with this approach.

Currently, the data is insufficient, and no high-quality evidence exists to recommend this technique in any thyroidectomy; the question of safety (surgical and oncological) is yet to be answered.

Both conventional and endoscopic thyroid surgeries require training and experience for a competent TORS thyroid surgeon. Actual and video case observations, cadaver dissection, and standardized tests for procedural sessions are part of a recommended teaching paradigm. Further difficulties include the fact that body habitus can make it difficult to expose the operative site. Finally, the cost of the equipment must be evaluated, which consists of the fixed cost of specialized retractors and the robot itself.

The use of remote access techniques in thyroid surgery is the latest frontier. Patient candidacy, safety, and resource utilization concerns have dampened initial enthusiasm for the remote access robotic thyroidectomy, and it is rapidly being abandoned in many centers. In specific specialized clinics, robotic-assisted thyroid surgery is still being perfected. The demand for this remote access, concealed approaches is still high among patients who value the esthetic benefits of thyroid surgery.

Contraindications for TORS

The ultimate purpose of these contraindications is to achieve good exposure for access and reduce vascular complications during and after the surgery by achieving adequate margins and ensuring the desired functional outcomes.

Many of the principles of endoscopic transoral laser surgery (TLM) apply to TORS trismus that prevent robotic access to the oral cavity. This obvious contraindication has fit exclusion criteria in multiple studies. However, certain factors predict adequate access referred to as 8 T’s by Rich et al., which include teeth, trismus, transverse dimensions (mandibular), tori, tongue, tilt, treatment (prior radiation), and tumor [39].

Preoperative imaging helps us to identify the primary tumor location, extension, and nodal status. Also, we can utilize this imaging to identify anatomical characteristics which would associate with adequate robotic access.

Luginbuhl et al. [40] identified specific markers for restricted access they are:

1. Distance from posterior pharyngeal wall to hyoid (≤ 30 mm)

2. The angle between the epiglottis and vertical plain of the larynx (≥ 130°)

3. Length from the posterior pharyngeal wall to the soft palate (≤ 8.1 mm)

Weinstein et al. proposed specific contraindications for TORS use in oropharyngeal surgery and categorized them into vascular, functional, oncological, and non-oncological [7].

Vascular contraindications to TORS for oropharyngeal cancer include the following:

1. Tumor epicenter in the midline tongue base which would put both the lingual arteries at risk

2. Tonsil malignancy with a retropharyngeal carotid artery

3. A tumor close to the carotid bulb or internal carotid artery that would expose the vessel

Functional contraindications to TORS for oropharyngeal cancer include the following:

1. Tumor resection requiring more than 50% of the deep tongue base musculature with or without epiglottis excision

2. Tumor resection requiring more than 50% of the posterior pharyngeal wall

Oncological contraindications to TORS for oropharyngeal cancer include the following:

1. All T4b cancers

2. Unresectable neck disease

3. Multiple distant metastases

Non-oncological contraindications to TORS for oropharyngeal cancer include the following:

1. Medical comorbidities which preclude the patient unfit for general anesthesia

2. Trismus prevents access to the oral cavity

3. Cervical spine disease that interferes with necessary positioning.

Drawbacks

The cost-effectiveness of robotic surgery has been questioned several times. Both immediate and ongoing costs must be considered when calculating expenditures. Despite increased usage in the head and neck, specific otolaryngologic equipment is infrequently used in the neck, as it is economically not feasible. For most cities, it is financially unviable. Surgical departments working together as a team and research grants can assist in offsetting some of the costs, individual specialists’ financial burdens, and subtracting the financial risk.

A downside of the present surgical robots is the loss of tactile perception of the tissues being worked on. The better visual information offered by the binocular camera, according to experienced robotic surgeons, substitutes for this to a great extent. Although sensory replacement methods such as a visible color scale on the monitor can help, accurate haptic feedback between the operator and the machine is still crucial.

Conclusion and Future Directions

Robotic head and neck surgery has transformed since its inception a decade back. The traditional morbid open approaches for accessing and resecting tumors of the oropharynx and supraglottic larynx are now being replaced with minimally invasive surgery in the form of TORS, with many reports suggestive of better functional outcomes following TORS.

As new robotic technology and unique surgical procedures for head and neck surgery and skull base surgery are developed, experimental surgical procedures incorporating automated technology are constantly expanding. Transaxillary, retroauricular, and modified facelift techniques are used to treat benign and malignant neck diseases. Salivary glands, congenital cysts, and lymph nodes can all be removed using these approaches, which are especially useful for patients with minimal disease. More research is needed to determine the boundaries of this surgical procedure and its benefits and drawbacks compared to open surgical approaches.

A proper selection of cases for TORS is the key to good functional results and to avoid triple therapy with surgery followed by adjuvant chemoradiation. Furthermore, the development of novel, flexible, miniaturized robots is likely to further expand the indications for TORS to tumors involving the glottic and subglottic larynx while driving down costs because of market competition.

Declarations

Conflict of Interest

The authors declare no competing interests.