*4.1.2 Transoral approaches*

For T1/T2 tumor, minimally invasive surgery with reducing morbidity has become a surgical option for patients. In addition to open surgery, a variety of transoral surgical techniques/instrumentation, such as laser, plasma, oral robot surgery, and so on, setting primary tumor resection as a rising feasible option, with preserving laryngeal function [69, 70]. Transoral surgery (TORS/TLM) are considered as promising alternatives with better functional consequence compared with open surgery. It presents fewer complications than open surgery with nasogastric tube dependence down from 31–3% within 1 year [71]. Supporters of surgery pose that the transoral method rise the laryngeal conservation rate by over 70% through lots of single-institution series [72, 73].

Over the past few decades, with growing prevalence in a transoral path for getting into the upper aerodigestive tract, especially transoral laser surgery (TOLS), which initially was used for cancer of the larynx, gradually spread to the hypopharyngeal tumor [72–76]. Local control and cancer-free survival rates via radiotherapy and open surgery inT1/T2 diseases have been achieved through transoral routes, especially in early-stage lesions [72, 77–80]. The procedural complications of TOLS include fistula, granulation tissue formation, and fatal bleeding. [77–80]. But, in other TOLS series reported, 83% of patients were received adjuvant treatment (radiotherapy or concurrent chemoradiotherapy) after TOLS according to pathologic outcomes [77–80]. In T3, T4 cases, because of the limitation of detailed data about the use of TOLS for these lesions, the potential effects (if any) of TOLS remains poorly explained [78, 79]. Transoral robotic surgery has been considered a valid treatment for early hypopharyngeal carcinoma [81–83]. Meanwhile, it is also regarded as more appropriate for early cases without adjuvant treatment [81].

The complete resection of the tumor should be taken as the premise, with the corresponding bilateral neck dissection, combining with intraoperative frozen section examination to achieve radical procedures. If the postoperative pathological or histological examination indicates high-risk factors, postoperative adjuvant radiotherapy is required.

## **4.2 Advanced-stage tumor (T3/T4 or** ≥ **N2)**

#### *4.2.1 Non-surgical management*

For the need of larynx-preservation, non-surgical treatments are considered as valid notions involved when appropriate [84]. At present, the non-operative treatment of larynx reservation is mainly combined with radiotherapy and chemotherapy (such as simultaneous radiotherapy and chemotherapy, induction chemotherapy sequential radiotherapy). Targeted therapy and immunotherapy are still being explored. The advanced patients involved postoperative adjuvant radiotherapy acquired improvement of local control, cancer-free survival rate, and overall survival [60, 85–88].

For stage IV malignancy, chemotherapy (induction therapy or concomitant therapy) heightens therapeutic efficacy, which is better in locoregional control and survival rates than radiation alone and combination therapies (surgery + radiation [84, 89–92]. A randomized trial including 202 cases indicated that chemotherapy group (induction chemotherapy +radiotherapy) achieve almost same disease survival as immediate surgery, with13.1% (the chemotherapy group) versus 13.8% (the surgery group) in a 10-year overall survival rate and with 8.5% versus 10.8% in10-year progression-free survival rates [93]. For optimizing chemotherapeutic effectiveness, organ-preservation strategies have to be abandoned in some advanced diseases in order to optimize chemotherapeutic effectiveness [94]. Pretreatment organ dysfunction, e.g., status vocal cord fixation and tracheostomy dependence, are related to posttreatment poor functional outcomes [95].

When considering organ-preservation strategy, the therapeutics must be implemented not only for saving of the anatomical units but also the return of upper aerodigestive function [96–98]. Meanwhile, the advanced patients with extensive invasion of surrounding tissue and serious decline of pharynx and larynx function present low pathologic complete response by non-operative treatment. The opinions of various disciplines should be integrated into decision-making. The American Society of Clinical Oncology (ASCO) guidelines recommend total laryngectomy for T3/T4patients with heavy tumor load and poor laryngeal function before induction chemotherapy [99].

#### *4.2.2 Surgery*

Surgery remains the preferred treatment for advanced-stage hypopharyngeal cancers [100]. Kinds of surgical manners are achieved in locally advanced cancers. Considering the possibility of aspiration after laryngeal preservation surgery, assessment of preoperative lung function is necessary. The cut margins (inferior or esophageal margin) must be extended carefully for safe boundaries. [25, 101, 102]. We should pay more attention to the extent of surgical margins, especially the inferior margin of the tumor (nearly to the esophageal part). Wide margins surgically are often considering in the skip disease and submucosal positive pathology. But researches have shown that patients did not benefit from extended edges (3–5 cm) compared with traditional (1–1.5 cm) incisal edges [103].

Partial pharyngectomy integrated with a partial laryngectomy, e.g.: vertical hemilaryngectomy, supraglottic laryngectomy, or supracricoid laryngectomy etc. is utilized in a series of hypopharyngeal cancers for hypopharyngeal cancers with small to medium lesions [104–107]. Laccourreye et share their extensive experience with the methods described above in their researches, including 135 cases with pyriform fossa lesions [104, 105]. The patients were executed supracricoid hemilaryngopharyngectomy combined with postoperative induction chemotherapy (IC) (96%). Five-year actuarial survival rates were assessed at 46.7%, with tracheostomy tubes removed in all patients (average = 9 days), and a 91.9% recovering oral intake (gastrostomy-free) at one year [105]. The conservation of competing cricoarytenoid units is important to achieve good functional outcomes. The unit comprises a single arytenoid, cricoid cartilage, ipsilateral recurrent/superior laryngeal nerves, and ipsilateral intrinsic laryngeal muscles. At least a single company should be reserved to obtain suitable swallowing function and upper respiratory function [108].

Due to roughly 10% of lesions invade the thyroid parenchyma directly, the cases with macroscopic cancer extension outside the larynx should be performed thyroid lobectomy or total thyroidectomy. In salvage treatments, considering thyroid vessel damages in response to radiation, preoperative hypothyroidism screening (routine pre- and post-operative thyroid hormone screening) is often necessary [109, 110]. In a prospective study including 137 laryngeal/hypopharyngeal patients, the incidence of hypothyroidism after treatment for laryngeal or hypopharyngeal tumors is 47.7%, especially after combination treatment [110]. Hypoparathyroidism is an important consideration in treatment, so the reservation or reimplantation of parathyroid glands must be noted during cricopharyngeal resection and/or paratracheal + mediastinal lymph node dissection [103].

#### *4.2.3 Reconstruction*

Laryngopharyngeal defect reconstruction is also an important approach for the surgeon to optimize surgery. The reconstruction presents a certain advantage in reducing the incidence of postoperative complications such as pharyngeal fistula, fatal bleeding, or infection. Meanwhile, it shows satisfactory outcomes in rehabilitating functions of speaking, swallowing, and breathing. The methods include local issue, regional flap or more vascularized free tissue transfer (**Figure 7**). Regional flaps contain the submental island flap, the supraclavicular island flap, the deltopectoral flap, the pectoralis, myocutaneous flap or latissimus dorsi myocutaneous flaps. Vascularized free tissue transfer methods include radial forearm free flap, anterolateral thigh free flap. In partial pharyngectomy with a partial laryngectomy, the small defects are repaired by local closure, and the larger defects (> 3 cm in size), regional flaps, and free tissue transfer are recommended. For partial pharyngeal defects

#### **Figure 7.**

*Surgical reconstruction of hypopharyngeal cancer involving the larynx and esophageal. (A) The tubular gastric reconstruction was applied to repair the esophagus by video-assisted thoracoscopic surgery (VATS). (B, C) Inset of the gastric tube into the operative cavity of total laryngopharyngectomy.*

with a total laryngectomy, despite other options, such as primary closure, primary closure with bolster flap, and regional tissue transfer, free tissue transfer has become one of the most utilized reconstructive selections. The major advantages of free tissue transfer are donor-site tissue, healthy tissue to repair circumferential defects. It is reconstructed in a tubular shape to provide a good swallowing tract and low incidence by avoiding entrance to other body cavities for total laryngopharyngectomy defects is usually rebuilt by the approaches such as enteric flap transposition, gastric pull-up, colonic Interposition, or jejunal free flap.
