Guidelines for the Treatment of Laryngeal Cancer from the Korean Society of Head and Neck Surgery

Abstract

Objectives.

Effective treatment of laryngeal cancer requires clinical decision-making that balances survival outcomes with the preservation of essential functions, such as voice and swallowing. This study, led by the Clinical Practice Guideline Committee of the Korean Society of Head and Neck Surgery, aims to establish evidence-based recommendations to guide surgeons in optimizing treatment decisions for patients with laryngeal cancer.

Methods.

A literature search was performed in the PubMed, Embase, Cochrane Library, and KoreaMed databases by a literature search expert and subsequently reviewed by a panel of 39 committee experts. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method was employed to assess the quality of evidence and develop and report the recommendations. The strength of each recommendation reflects the guideline panel’s confidence that the benefits of an intervention outweigh its risks for the target population. After drafting the guidelines, Delphi questionnaires were distributed to members of the Korean Society of Head and Neck Surgery and an external reviewer panel.

Results.

In total, 15 evidence-based recommendations are provided, addressing six critical aspects of laryngeal cancer treatment: early-stage treatment, treatment of locally advanced cancer, neck management, adjuvant therapy, swallowing rehabilitation, and salvage treatment for recurrent tumors.

Conclusion.

The guidelines provide evidence-based, validated recommendations to support clinicians in making optimal treatment decisions for laryngeal cancer.

INTRODUCTION

According to statistical data from the Korean National Cancer Center, the prevalence rate of laryngeal cancer in 2021 was 24.7 cases per 100,000 individuals [1]. Although its incidence has gradually declined in tandem with decreasing smoking rates, laryngeal cancer remains a significant public health concern. The National Comprehensive Cancer Network (NCCN) guidelines outline both surgical and nonsurgical treatment approaches for laryngeal cancer [2]. Historically, surgical interventions, especially total laryngectomy (TL), have adversely affected patients’ quality of life due to the loss of voice. In response, non-surgical, organ-preserving strategies emerged as standard treatment modalities based on randomized controlled trials (RCTs), such as those conducted by the Veterans Affairs Administration and the Radiation Therapy Oncology Group (RTOG 91-11) [3,4]. Nonetheless, concerns regarding inferior survival outcomes with non-surgical approaches underscore the need for precise clinical decision-making [5-7].

To address these challenges, the Korean Society of Thyroid-Head and Neck Surgery (KSTHNS) developed surgical treatment guidelines for laryngeal cancer in 2017 [8]. These guidelines, primarily based on narrative literature reviews and expert consensus, included 62 recommendations across 32 categories. Although they significantly advanced clinical practice, the need for more robust, evidence-based guidelines soon became apparent.

Recently, the Korean National Cancer Center initiated a project to develop evidence-based clinical practice guidelines for laryngeal cancer treatment using systematic reviews, meta-analyses, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Comprehensive methodological consultations during the development process revealed that the current clinical practice guidelines did not adequately address certain topics covered in the 2017 guidelines [8]. Therefore, these new guidelines are not intended as an update to the earlier surgical treatment guidelines but rather as a complementary resource. The systematic approach and evidence-based recommendations derived from key questions (KQs) and meta-analyses are expected to support clinical decision-making effectively. It is important to note that these guidelines are intended to supplement, not replace, clinical judgment or resolve medico-legal issues; they serve as an adjunct to sound clinical reasoning.

MATERIALS AND METHODS

Target population

These guidelines apply to patients diagnosed with laryngeal cancer who have either early-stage or locally advanced disease and are candidates for curative-intent treatment via surgery, radiation therapy (RT), or chemoradiotherapy. Patients with systemic metastases or unresectable disease due to extensive local progression are excluded.

Organization of the committee

The guidelines were developed by the Guideline Committee of the Korean Society of Head and Neck Surgery (KSHNS). A task force comprised five teams, totaling 39 experts, was appointed. The task force chairman (JOP) and vice-chairman (JYJ) were designated by the President of KSHNS (KJC), with the Committee’s approval. The committee received support from a literature search expert and a methodology expert from the Korean Cancer Management Guideline Network (KCGN) to optimize protocols for literature search, systematic review, meta-analysis (if applicable), and guideline development methodologies. Committee members convened via conference calls and regularly scheduled online or face-to-face meetings to review and evaluate each stage of the guideline development process.

Literature search and quality assessment

A systematic literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search expert searched the PubMed, Embase, Cochrane Library, and KoreaMed databases between December 25, 2022, and April 17, 2023, using relevant keywords—including MeSH and Emtree terms—and Boolean operators (AND, OR, NOT) to refine the strategy. The retrieved studies underwent screening and eligibility assessment to exclude duplicates, irrelevant studies, and those lacking sufficient comparisons or details. The selection process followed two approaches based on the availability of systematic reviews for each KQ: (1) If an appropriate systematic review was identified for a KQ, the studies it included were used in guideline development, supplemented by additional original studies published after the review’s search period to ensure up-to-date evidence; (2) If no systematic review was available for a KQ, a comprehensive search for original studies covering the entire period was performed.

Two committee members independently reviewed the final study selection to determine inclusion or exclusion. The search strings for each KQ and the number of retrieved documents are provided in Supplementary Material 1, and the final PRISMA table for each KQ appears in Supplementary Material 2.

Quality assessment of the literature, meta-analysis, and the grading of recommendations

GRADE approach was used to assess evidence quality and develop and report recommendations. Prior to the guideline meeting, committee members received training on this process through online modules, publications, and presentations, supported by the KCGN. Among the selected studies, the quality of systematic reviews was evaluated using A Measurement Tool to Assess Systematic Reviews (AMSTAR) II [9]. The Risk of Bias for Non-randomized Studies (RoBANS) II tool was applied to assess non-RCTs and observational studies, while the Cochrane Risk of Bias (RoB) 2.0 tool was used for RCTs [10,11]. Two committee members independently assessed the quality of the evidence, and any disagreements were resolved through discussion. The final quality assessment results are summarized in Supplementary Material 3.

Meta-analyses were performed for KQs with sufficient data for evidence synthesis. This encompassed KQs A1, A2, B1, C1, D1, and F2 (Table 1). Meta-analysis and statistical analyses were conducted using Review Manager (RevMan) version 5.3 (The Cochrane Collaboration). Summary statistics for dichotomous outcomes were based on unadjusted odds ratios (ORs) and adjusted hazard ratios (HRs) with 95% CIs. Heterogeneity was assessed using the I² statistic, and effect sizes were pooled using a random-effects or fixed-effects model, depending on the heterogeneity level. A P-value of <0.05 was considered statistically significant.

Table 1.

Organization of the KSHNS guidelines for the treatment of laryngeal cancer

Location key	Section	Item
A	Treatment for early-stage (T1–T2) laryngeal cancer
A1	What is the appropriate treatment for early-stage glottic cancer?	R1-2
A2	What is the appropriate treatment for early-stage supraglottic cancer?	R3-4
B	Treatment for locally advanced laryngeal cancer (T3–T4)
B1	What is the role of total laryngectomy in locally advanced laryngeal cancer?	R5
B2	What is an appropriate larynx-preservation therapy in locally advanced laryngeal cancer?	R6
C	Management of the neck
C1	Is prophylactic neck dissection necessary for patients with clinically lymph node-negative laryngeal cancer?	R7-9
C2	What is the appropriate extent of neck dissection in patients with clinically lymph node-positive laryngeal cancer?	R10-12
D	Adjuvant therapy
D1	Does adjuvant therapy improve treatment outcomes in patients with laryngeal cancer following surgical resection?	R13
E	Swallowing rehabilitation
E1	What is the role of swallowing rehabilitation in patients with laryngeal cancer?	R14
F	Salvage treatment for recurrent laryngeal cancer
F1	What are the salvage treatment options for locally recurrent laryngeal cancer?	R15
F2	Does elective neck dissection improve oncological outcomes in salvage treatment for locally recurrent laryngeal cancer?	R16

KSHNS, Korean Society of Head and Neck Surgery.

Each recommendation’s level of evidence was determined according to the GRADE criteria. High-level evidence indicates strong confidence that the estimated effect approximates the true effect, while moderate evidence suggests that the estimate is likely close to the actual effect, although some variation is possible. Low evidence reflects significant uncertainty, and very low evidence (derived from expert consensus) indicates that no direct evidence is available, with recommendations based solely on the formal agreement of the guideline committee.

The Delphi method was used to establish consensus, particularly regarding the balance of benefits and harms. A panel comprising KSHNS members and five multidisciplinary consultation experts reviewed the recommendations using an online questionnaire. Sixteen recommendations were presented, and panel members were asked to indicate their agreement by selecting “fully agree,” “agree,” “neither agree nor disagree,” “disagree,” or “totally disagree.” A recommendation was accepted if at least two-thirds of the panel responded with “fully agree” or “agree.” In the first round, 66 responses were received, achieving consensus on 15 of the 16 recommendations. The recommendation that did not meet the threshold was revised based on expert feedback and redistributed for a second round, in which 42 experts participated. The remaining recommendation was subsequently finalized through panel consensus.

GUIDELINES

Table 1 summarizes the organization of the Guidelines for the Treatment of Laryngeal Cancer, and a summary of the recommendations is provided in Supplementary Material 4.

A. Treatment for early-stage (T1–T2) laryngeal cancer

A1. What is the appropriate treatment for early-stage glottic cancer?

Recommendation 1

For early-stage glottic cancer, both surgical treatment and radiation therapy can be considered as initial treatment. (Strong recommendation, low-quality evidence)

Recommendation 2

Transoral surgery is the preferred surgical treatment method in early-stage glottic cancer. (Conditional recommendation, low-quality evidence)

The primary goal in treating early glottic cancer (T1–T2) is to achieve local disease control while preserving the larynx and its functions, particularly voice. The principal treatment modalities include transoral laser surgery (TOS), open partial laryngectomy, and external radiation therapy (XRT) [12-15]. Open partial laryngectomy, which encompasses vertical partial laryngectomy and supracricoid partial laryngectomy, has demonstrated oncological outcomes comparable to those of TOS and XRT in early-stage laryngeal cancer [14,16-18]. However, open partial laryngectomy inevitably results in morbidities such as dysphagia and scarring and is generally reserved for patients with contraindications to XRT, recurrent disease, poor laryngeal exposure, or anterior commissure involvement. Consequently, this study excludes patients treated with open partial laryngectomy.

Due to the anatomical structure and the limited submucosal lymphatic networks, cervical lymph node treatment is generally not performed in early glottic cancer, in contrast to other laryngeal subsites [19,20]. The NCCN guidelines for early-stage glottic cancer advocate an organ-preserving strategy—either surgery (with or without neck dissection) or XRT. Numerous studies comparing TOS and XRT have reported similar local control and survival rates, suggesting that posttreatment functional preservation should be a key consideration when selecting a treatment modality for early-stage glottic cancer.

Based on a review of 34 studies, we conducted a meta-analysis comparing the effectiveness of these two treatment modalities [21-54]. The analysis evaluated oncological outcomes, posttreatment voice quality, and other adverse effects, such as the incidence of secondary primary cancers and the overall laryngeal preservation rate (LPR). Oncologically, the local control rate (LCR) for early-stage laryngeal cancer is typically reported to be around 90% [22,55]. Nonetheless, debate persists regarding the oncological superiority of specific treatment modalities, largely due to the lack of RCTs. According to our meta-analysis, TOS yielded better 5-year overall survival (OS) outcomes (risk ratio [RR], 0.744; 95% CI, 0.671–0.825) [28,29,31,34,36,37,39,41,45,46,50,52]. However, no statistically significant differences were observed between the two groups in terms of disease-specific survival (DSS; RR, 0.825; 95% CI, 0.591–1.152) or disease-free survival (DFS; RR, 1.051; 95% CI, 0.724–1.526). These results are consistent with previous comparative studies and indicate that a definitive oncological superiority between TOS and XRT could not be established.

Regarding residual voice impairment after treatment, TOS typically affects vocal fold vibration by creating surgical scars, and the resulting tissue loss can cause a glottal gap, thereby impairing the voice. This effect is generally correlated with the extent of tissue excision [38]. In contrast, XRT is reported to alter vocal fold vibration by inducing dryness and fibrosis [56]. Prior research has often suggested that XRT yields superior voice outcomes compared to surgical treatment [12,57,58]. Our meta-analysis compared subjective assessments using the Voice Handicap Index and objective voice parameters—including fundamental frequency (F0), jitter, shimmer, noise-to-harmonic ratio, and maximal phonation time (MPT) [21,24,27,31-33,35,38-40,43,45,47,49,51,53]. MPT was evaluated in eight studies, and after excluding one heterogeneous study, it was found to be lower in the TOS group compared to the XRT group (standardized mean difference, −0.748; 95% CI, −1.133 to −0.364). However, no significant differences were noted between the two groups for the other voice parameters.

Regarding adverse effects following treatment, one study evaluated the frequency of secondary primary tumors and the need for salvage laryngectomy during the posttreatment follow-up period. A meta-analysis of six studies examining secondary primary tumors found no statistically significant difference in risk between the two treatment groups (RR, 1.007; 95% CI, 0.442–2.297) [35-37,44,46,48]. However, in the case of salvage laryngectomy, the TOS group exhibited significantly lower risk of undergoing the procedure compared to the XRT group (RR, 0.521; 95% CI, 0.334–0.812), with low heterogeneity observed among the studies (I², 33%; tau², 0.5088; P=0.10). These findings are consistent with previous meta-analyses [55,59]. Guimaraes et al. [59] reported that during the posttreatment observation period, individuals in the surgery group had a 1.8% probability of undergoing salvage laryngectomy, whereas those in the XRT group had an 11.8% probability.

We did not find convincing oncological evidence favoring either TOS or XRT. Likewise, aside from MPT, no significant differences were identified in voice-related outcomes—although heterogeneity in measurement timing across studies limited the precision of MPT conclusions. Notably, the rate of salvage TL, which reflects laryngeal preservation, was significantly lower in the TOS group, consistent with previous findings. Overall, most studies included in the meta-analysis were retrospective and carried a high risk of bias. Oncologically, both surgery and RT produced comparable outcomes, each offering distinct advantages and disadvantages regarding voice preservation and recurrence. Given that both treatments achieved survival rates exceeding 90% for early glottic cancer in most studies, we strongly recommend either treatment option.

A2. What is the appropriate treatment for early-stage supraglottic cancer?

Recommendation 3

For early-stage supraglottic cancer, both surgical treatment and radiation therapy can be considered as initial treatment. (Strong recommendation, low-quality evidence)

Recommendation 4

Conservative laryngeal surgery (transoral surgery or open partial laryngectomy) can be considered as a surgical treatment option for early-stage supraglottic cancer. (Conditional recommendation, low-quality evidence)

For patients with early-stage supraglottic cancer (T1–T2), successful disease control can be achieved through either conservative laryngeal surgery (open partial laryngectomy or TOS) or therapeutic doses of XRT [8,60]. The key factors when selecting initial treatment include improving survival, reducing recurrence, and preserving laryngeal function.

Regarding the comparative effectiveness of surgical treatment and XRT, Patel et al. [61] conducted a systematic literature review and meta-analysis of seven retrospective studies [60,62-67]. Their analysis indicated that disease-specific mortality (OR, 0.43; 95% CI, 0.31–0.60) and 5-year overall mortality (OR, 0.40; 95% CI, 0.29–0.55) were lower in the surgical group than in the XRT group, while the local recurrence rate did not differ significantly between the two [61].

Among the studies in this meta-analysis, Arshad et al. evaluated the largest cohort (2,631 patients) and found that organ-preserving surgery with lymph node dissection resulted in a significantly better survival rate than XRT alone, suggesting that surgical treatment is preferable for early-stage supraglottic cancer [62]. Conversely, Spriano et al. [60] reported a 5-year DFS rate of 88.4% for conservative laryngeal surgery versus 76.4% for radiotherapy in T1–T2 supraglottic cancer (166 patients), without a statistically significant difference. This study also noted that complications related to chronic aspiration occurred in 3% of patients undergoing conservative surgery, with a higher risk in those receiving more extensive surgery than in those treated with XRT [60]. Since all the studies included in the meta-analysis were retrospective, the level of evidence is very low, making definitive conclusions difficult.

Overall, there is no significant evidence-based difference in oncologic outcomes between surgical treatment and XRT for early-stage supraglottic cancer (T1–T2). Moreover, no study has yet compared the functional outcomes of these two modalities. Therefore, taking into account both patient-specific factors and the benefits and risks of treatment, surgical treatment and RT remain viable initial options; the most appropriate choice should be determined through shared decision-making between the treatment team and the patient.

B. Treatment for locally advanced laryngeal cancer (T3–T4)

B1. What is the role of total laryngectomy in locally advanced laryngeal cancer?

Recommendation 5

Total laryngectomy can be selected as an initial treatment in locally advanced laryngeal cancer to achieve better locoregional control and survival. (Conditional recommendation, low-quality evidence)

The larynx is essential for respiration, phonation, and swallowing; therefore, in advanced laryngeal cancer, survival must be balanced with functional preservation. TL, the primary surgical treatment modality for locally advanced laryngeal cancer, inevitably leads to a significant decline in quality of life [68,69]. Following prospective randomized trials on laryngeal preservation—including studies by the Veteran’s Affairs [3] and RTOG 91-11 [4], which demonstrated that primary RT and chemoradiation were not inferior to surgery—laryngeal preservation treatments have become a dominant modality in managing locally advanced laryngeal cancer [70,71]. However, because these preservation treatments have not independently improved survival [69,70], the optimal primary treatment modality remains debated.

A number of studies have compared oncologic outcomes of TL and organ preservation treatments in locally advanced laryngeal cancer. We conducted a meta-analysis evaluating OS, DFS, DSS, and locoregional control (LRC). Our analysis of 17 studies revealed that primary TL significantly reduced risk compared to concurrent chemoradiation therapy (CCRT) for patients with T3 and T4 stages (HR, 0.77; 95% CI, 0.66–0.90; P<0.00001) [6,71-83]. In a subgroup analysis for T4 stage, the risk for reduced OS was significantly higher in the CCRT group compared to the TL group (HR, 1.40; 95% CI, 1.20–1.57; P<0.00001) [6,70,73,78,81,82]. These findings are consistent with previous studies, which consistently show the superiority of primary TL for OS in T4-stage disease [69-71,78,83]. Current NCCN guidelines also recommend primary surgery as the preferred treatment for T4a patients [2]. Additionally, in a meta-analysis of five studies on LRC, the primary TL group demonstrated a significantly lower risk compared to the CCRT group (HR, 0.58; 95% CI, 0.38–0.88; P=0.01) [74,76,77,82,84], although stage-specific subgroup analysis was not feasible. No significant differences between TL and CCRT were observed for DFS and DSS, and stage-specific analysis could not be performed [71-74,76,77,85-87].

Uncertainty remains regarding the management of T3 disease. In our meta-analysis of OS for T3 cases, no significant difference was found between the primary TL and CCRT groups (HR, 1.19; 95% CI, 0.83–1.70; P=0.33) [70,73,81], which is consistent with prior analyses and systematic reviews [69,70,83]. The NCCN guidelines also consider non-surgical treatment modalities as equally feasible for T3 cases, including those potentially suitable for TL [88].

Studies on quality of life have consistently highlighted that TL results in loss of natural phonation and introduces psychological and social challenges due to the creation of a permanent tracheostomy [68-71,78,83,89,90]. Furthermore, during treatment decision-making, patients may refuse such life-altering surgery or have comorbidities—especially in older patients—that make aggressive surgery less tolerable [78]. Conversely, non-surgical treatments also come with quality-of-life concerns, such as dietary restrictions caused by radiation-induced oral mucositis and xerostomia [89], and a lower rate of improvement in dysphagia in the CCRT group compared to the surgical group (75.4% vs. 53.8%, P<0.001) [90]. Ganly et al. [91] reported that salvage TL performed after initial CCRT failure was associated with significantly higher local complications due to delayed wound healing (45% vs. 25%, P=0.02) and increased rates of pharyngocutaneous fistula (53% vs. 36%, P=0.08) compared to initial TL.

In summary, although debate persists over the initial application of TL versus laryngeal-preserving treatments, the superior OS outcomes and lower local recurrence rates observed with TL support its use as an initial treatment for locally advanced laryngeal cancer, especially in T4-stage disease. However, because surgical feasibility and tolerance for postoperative quality-of-life reductions vary among patients, treatment choice must consider factors such as whether the disease is T3 or T4, the patient’s need for voice function in social activities, age, and comorbidities. Therefore, the recommendation remains conditional. Therefore, a careful selection of initial treatment modalities, tailored to individual patient characteristics and disease burden, is crucial for achieving the optimal balance between oncologic outcomes and quality of life in the management of locally advanced laryngeal cancer.

B2. What is an appropriate larynx-preservation therapy in locally advanced laryngeal cancer?

Recommendation 6

(A) Larynx-preservation therapy (concurrent chemoradiation therapy or larynx-preservation surgery) can be applied depending on the patient’s condition (T stage, age, underlying diseases, social activities, etc.). (Conditional recommendation, low-quality evidence)

(B) Larynx-preservation surgery can be performed in selected T3–T4 cancers without extensive tongue base invasion, bilateral cricoarytenoid unit impairment, or inferior extension to the cricoid cartilage, although the risk of postoperative morbidity such as dysphagia and aspiration should be carefully considered. (Conditional recommendation, low-quality evidence)

Managing locally advanced laryngeal cancer (T3–T4) presents significant challenges. This discussion is based on a comprehensive review of treatment options, with a focus on larynx-preservation therapies compared to TL. TL is often regarded as the standard treatment for T4 tumors because of its superior OS and local control outcomes. Previous studies have shown that TL reduces the risk of death compared to CCRT [69,71,83,92]. Specifically for T4 tumors, TL demonstrated significantly better OS than CCRT [69,70,92]. In contrast, CCRT is a viable option for T3 tumors, providing oncologic outcomes comparable to TL; in subgroup analysis, no significant OS difference was observed between TL and CCRT for T3 tumors [69,70]. CCRT is especially beneficial for patients prioritizing laryngeal function preservation or those at high surgical risk. A recent meta-analysis found no significant difference in DFS between TL and CCRT, although heterogeneity was moderate (I²=69%) [69]. Similarly, no significant difference in DSS was observed between TL and CCRT (with high heterogeneity, I²=89%) [69,71], while TL achieved better local control than CCRT with low heterogeneity (I²=20%) [69].

The choice of therapy for locally advanced laryngeal cancer should be individualized, taking into account patient-specific factors and tumor characteristics such as age, comorbidities, lung and swallowing function, and the extent of local invasion and nodal involvement [93]. Partial laryngectomy may be considered for selected T3–T4 tumors that do not invade critical structures extensively; in selected cases, partial laryngectomy has shown oncologic outcomes comparable to TL and CCRT [94]. A recent study suggests that surgery with adjuvant therapy is preferred for patients with T4a tumors, whereas patients with T3 tumors can be managed with either surgery or definitive CCRT/RT to preserve laryngeal function [83].

Recent advances in transoral surgery, including laser surgery and transoral robotic surgery (TORS), have shown promise as effective larynx-preservation strategies in locally advanced laryngeal cancer [95,96]. These minimally invasive techniques offer benefits such as reduced surgical morbidity, shorter recovery times, and potentially better functional outcomes regarding voice and swallowing. Laser surgery enables precise tumor excision with minimal damage to adjacent tissues, while TORS provides improved visualization and dexterity. For selected patients, these approaches may serve as useful alternatives, preserving laryngeal function without compromising oncologic control. However, their indications and long-term oncologic safety have not yet been fully established.

In conclusion, while TL offers superior outcomes for T4 tumors, CCRT and partial laryngectomy provide viable alternatives for T3 or selected T4 cases, allowing laryngeal function to be preserved without sacrificing oncologic control. This tailored approach is essential for optimizing outcomes in patients with advanced laryngeal cancer.

C. Management of the neck

C1. Is prophylactic neck dissection necessary for patients with clinically lymph node-negative laryngeal cancer?

The indications and extent of prophylactic neck dissection or irradiation in patients with clinically lymph node–negative laryngeal cancer remain topics of ongoing debate. The decision to pursue prophylactic neck treatment is typically based on the primary subsite of laryngeal cancer, its T stage, and the estimated risk of occult lymph node metastases (LNM). Directly analyzing the impact of neck dissection extent on survival in laryngeal cancer is challenging; therefore, indirect evidence was derived by examining the pooled incidence of LNM at each neck level. Prophylactic treatment is generally considered when this risk reaches 15%–20% or higher. The risk varies by primary site and stage, with glottic cancers typically exhibiting sparse lymphatic drainage and a lower incidence of occult LNM [97]. Expected survival benefits, as well as potential functional and cosmetic morbidity from prophylactic treatment, are comprehensively considered for each patient.

Recommendation 7

If lymph node metastasis is clinically negative in early-stage (T1–T2) laryngeal cancer confined to the glottis, prophylactic neck dissection is not mandatory. (Conditional recommendation, low-quality evidence)

The initial search identified 868 studies on occult neck LNM in laryngeal cancer. Among these, only 10 studies specifically addressed glottic cancer, encompassing a total of 2,192 patients [97-106]. Regardless of T stage, the overall pooled incidence of occult metastasis in glottic cancer was 9% (95% CI, 5.6–14.7; I²=91%). In five studies reporting data on the T1–T2 stage [97,99-102], the pooled incidence was 6% (95% CI, 0.1–12; I²=88%). For the subgroup with T3 stage of glottic cancer [98-102], the pooled incidence was 15.6% (95% CI, 7.6–23.6; I²=30%). For T4 stage disease [98-102], the pooled incidence was 46.5% (95% CI, 20.6–72.4; I²=67%).

Recently, with the introduction of non-surgical organ preservation treatments such as definitive RT and transoral surgery for early-stage glottic cancer, avoiding unnecessary neck dissection and minimizing the radiation field have become increasingly important to prevent treatment-related morbidities [107], In this context, the low probability of occult neck LNM in T1–T2 glottic cancer suggests that prophylactic neck dissection may be omitted. This approach helps to avoid unnecessary procedures and potential complications, thereby preserving the patient’s quality of life.

However, these results do not directly assess the impact of prophylactic neck dissection on survival. The decision to perform neck dissection should be based on various clinical factors, and therefore, the strength of the recommendation remains conditional.

Recommendation 8

If lymph node metastasis is clinically negative in early-stage (T1–T2) laryngeal cancer involving the supraglottis, prophylactic neck dissection including levels II–III can be considered. (Conditional recommendation, low-quality evidence)

The lymphatic drainage of the larynx differs significantly between the supraglottic and glottic regions. The supraglottis has a dense lymphatic network that drains via the thyrohyoid membrane into the first-echelon lymph nodes at levels II and III. In contrast, the glottis—particularly the free edge of the true vocal cords—has a sparse lymphatic network and is nearly devoid of lymphatic vessels. Since the 1960s, several studies have highlighted these differential drainage patterns, emphasizing the rich lymphatic presence in the supraglottis compared to the minimal lymphatic structures in the vocal cords [108-110].

In our analyses, 23 studies specifically addressing supraglottic cancer, with a total of 2,235 patients, were reviewed [100-102,111-130]. In T1–T2 tumors, the pooled incidence of occult LNM was 15.1% (95% CI, 12–18.3; I²=0%). For the subgroup of T3 supraglottic cancer, the pooled incidence of occult metastasis was 23.1% (95% CI, 16.6–29.7; I²=65%). Given the higher incidence of LNM in supraglottic cancer compared to glottic cancer at similar T classifications (15.1% vs. 6% in T1–T2 tumors and 23.1% vs. 15.6% in T3 tumors), prophylactic neck dissection may be warranted in early-stage (T1–T2) supraglottic cancer. This increased risk underscores the importance of addressing potential lymph node involvement to ensure comprehensive treatment and improve patient outcomes.

Our analysis further indicates a pooled incidence of 0.8% (95% CI, 0–3.3; I²=48%) for level I and only 1% (95% CI, 0–3.3; I²=48%) for level IV, suggesting that routine elective treatment of these levels may be unnecessary. Similarly, the pooled incidence for level V was 2.3% (95% CI, 1.1–3.5; I²=37%), which supports their exclusion from routine dissection.

Recommendation 9

If lymph node metastasis is clinically negative in advanced stage (T3–T4) laryngeal cancer, prophylactic neck dissection including levels II–III should be considered. (Conditional recommendation, low-quality evidence)

Twenty studies on laryngeal cancer without specifying a subsite—including a total of 3,916 patients—were reviewed [102,131-149]. The pooled incidence of occult neck LNM in advanced-stage (T3–T4) laryngeal cancer was 20.8% (95% CI, 15.5–26.1; I²=61%). This substantial risk supports the need for prophylactic neck dissection in patients with advanced-stage laryngeal cancer who do not exhibit clinically apparent ipsilateral neck LNM. The increasing risk of occult metastases with advancing T stage highlights the importance of this approach in ensuring comprehensive treatment and improving patient outcomes.

C2. What is the appropriate extent of neck dissection in patients with clinically lymph node-positive laryngeal cancer?

Recommendation 10

If ipsilateral lymph node metastasis is clinically evident, comprehensive neck dissection or selective neck dissection including at least levels II, III, and IV should be performed. (Strong recommendation, low-quality evidence)

Although no large-scale randomized studies have established the optimal treatment for laryngeal cancer with clinically positive LNM, modified radical neck dissection (MRND) involving levels I–V is commonly performed. However, studies indicate that metastasis to levels I (1.8%–5%) and V (2%–11%) is infrequent in laryngeal cancer [131,150,151]. Allegra et al. [152] reported neck recurrence in 6 of 58 patients (10.3%) with laryngeal cancer and LNM who underwent selective neck dissection (SND)—all within previously dissected areas. Similarly, Lohuis et al. performed SND including levels II–V in 48 patients with laryngeal and hypopharyngeal cancer, reporting six cases of recurrence, five of which occurred within previously dissected regions [151]. Brazilian Head and Neck Cancer Study Group [153] compared MRND and SND (levels II–V) in 132 patients with T2–T4N0M0 supraglottic and transglottic cancer and found no significant differences in 5-year survival, recurrence rate, complications, or hospital stay. However, Santos et al. [154] reported higher neck recurrence rates after SND in patients with T3 or higher primary tumors and N2b or higher neck metastasis, advising caution in such cases. Furthermore, when extranodal extension (ENE) is present, resection of the spinal accessory nerve, internal jugular vein, and sternocleidomastoid muscle may be necessary.

A literature search on LNM for unilateral neck dissection in supraglottic cancer yielded only a few studies. In an earlier study, Candela et al. [131] found that metastasis in laryngeal cancer was most common in levels II–IV. In supraglottic cancer with clinical LNM, 5% and 6% of 119 patients had metastasis in levels I and V, respectively, while postoperative confirmation showed 11% in level I and none in level V. Choi et al. [155] analyzed 78 cases (39 of which were supraglottic cancer) and noted that the two cases with level I metastasis were salvage surgeries; both node-negative and node-positive patients had very low frequencies of level I involvement. Consistent with this, Buckley and MacLennan [156] and Gallo et al. [157] reported that most metastases in laryngeal cancer occurred in levels II–V, with few cases at levels I and V. Multiple other studies have also indicated a low frequency of metastasis at levels I and V [158-162]. However, most of these studies were retrospective and lacked bias assessments, making the evidence low-quality. Nevertheless, given the high probability of metastasis in levels II, III, and IV when lymph node involvement is present, performing neck dissection that includes at least these levels is necessary, warranting a strong recommendation.

Recommendation 11

If ipsilateral lymph node metastasis is clinically apparent in laryngeal cancer confined to the glottis, contralateral prophylactic neck dissection is not mandatory. (Conditional recommendation, low-quality evidence)

Prophylactic neck dissection in head and neck cancer is generally considered when the rate of occult metastasis is 15%–20% or higher. If the tumor crosses the midline and invades the contralateral side, elective treatment of the contralateral neck may be necessary [8]. In locally advanced glottic cancer (T3–T4) that extends beyond the midline, and in transglottic cancer—which involves both the supraglottic and subglottic regions—the lymphatic spread pattern may be similar to that of primary cancers in these areas, suggesting that contralateral prophylactic neck dissection could be warranted.

Amar et al. [163] studied 104 laryngeal cancer patients who underwent surgery and found that in unilateral glottic cancer without midline involvement, the contralateral occult metastasis rate was only 3.5%, suggesting that contralateral prophylactic dissection is unnecessary. Bottcher et al. [147] investigated occult metastasis rates in 28 advanced laryngeal cancer patients who underwent TL with prophylactic neck dissection for transglottic cancer, finding occult metastasis in 24.9% of cases— 14.2% on the ipsilateral side and 10.7% on the contralateral side. They also noted that previous studies observed no contralateral metastasis when the primary tumor did not cross the midline [164].

Given these rates, current evidence does not support routine contralateral prophylactic neck dissection in glottic cancer with ipsilateral lymph node metastasis. However, due to the lack of well-designed prospective comparative studies, the level of evidence remains low and the recommendations are conditional.

Recommendation 12

If ipsilateral lymph node metastasis is clinically apparent in laryngeal cancer involving the supraglottis, contralateral prophylactic neck dissection including levels II-IV should be considered. (Conditional recommendation, moderate-quality evidence)

Studies on prophylactic contralateral neck dissection in supraglottic cancer consistently show that surgery reduces recurrence and improves survival compared to observation, without significantly increasing complications. Ferlito et al. [160] found that prophylactic contralateral neck dissection improved survival and recurrence management. Weber et al. [165] reported a recurrence rate of 20% in the observation group compared to 9% in the surgical group, with 2-year survival rates of 76% versus 72%, respectively, favoring surgery. Gallo et al. [157] analyzed 24 surgical versus 103 observational cases, noting that 9 of 24 had pathologic lymph node metastasis while 40 of 103 in the observation group developed local recurrence; however, 5-year survival rates did not differ significantly. Chiu et al. [166] compared 202 observational with 115 surgical cases, demonstrating a lower 2-year recurrence rate (7.8% vs. 20%) and higher 2-year survival (83% vs. 72%) in the surgical group. Although these studies were retrospective, each included over 100 patients and provided moderate-level evidence.

Regarding the extent of surgery, Bottcher et al. [147] reported contralateral neck metastasis only in levels IIA, III, and IV, although their analysis was limited to six patients. Gross et al. [167] analyzed 65 patients and found that approximately 20% had metastasis in contralateral level IIB, suggesting that surgical intervention in this area may be necessary. Dundar et al. [168] observed that contralateral level IIB metastasis occurred only when level IIA was also involved, making intraoperative detection challenging because preoperative assessments showed no LNM. Additional studies generally support performing lymph node dissection in contralateral levels II–IV [129,169,170].

Regarding complications of contralateral prophylactic neck dissection, two retrospective studies compared complication rates in supraglottic cancer patients with unilateral neck metastasis who underwent selective dissection versus observation. Gregor et al. [171] found no significant differences in complications or sequelae between the groups. Similarly, Gallo et al. [157] compared 24 surgical and 103 observational cases and reported no significant differences in complications or 5-year survival rates between the two groups. The surgical procedure typically involves SND of levels II–IV, with potential complications including injury to the spinal accessory nerve.

D. Adjuvant therapy

D1. Does adjuvant therapy improve treatment outcomes in patients with laryngeal cancer following surgical resection?

Recommendation 13

(A) Adjuvant therapy (radiation therapy or chemoradiation therapy) following radical surgery can be considered for patients with advanced stage (III–IV) disease and/or risk factors such as vascular invasion, perineural invasion, or multiple nodal metastases. (Conditional recommendation, low-quality evidence)

(B) Adjuvant chemoradiotherapy should be considered for patients with laryngeal cancer and positive surgical margins or extranodal extension. (Conditional recommendation, high-quality evidence)

Although the optimal adjuvant therapy strategy (radiation versus chemoradiation) after radical surgery for advanced laryngeal cancer remains unclear, its benefits in stage III and IV head and neck squamous cell carcinoma (HNSCC) are well established [172-175]. A meta-analysis assessing the impact of adjuvant RT in advanced laryngeal cancer identified 13,359 abstracts from multiple databases (PubMed, Embase, Cochrane Library, KoreaMed) using terms related to laryngeal cancer and radiotherapy. After screening, three studies were included. Despite high heterogeneity (I²=78%), patients who underwent postoperative RT (n=596) showed significantly improved 5-year OS compared to those who had surgery alone (n=930) (RR, 0.90; 95% CI, 0.84–0.97) [92,176,177]. Additionally, postoperative RT reduced recurrence rates (RR, 0.36; 95% CI, 0.14–0.90; I²=0%) [176,177]. These findings suggest that adjuvant RT after radical surgery improves clinical outcomes in advanced laryngeal cancer. However, in pT3N0 laryngeal cancer without other adverse pathological features, its use should be carefully weighed against potential risks [175,92].

Previous studies have identified high-risk factors that benefit from adjuvant therapy after HNSCC surgery, including ENE, positive or close margins, pT3/pT4 primary tumors, pN2/pN3 nodal disease, perineural invasion, vascular invasion, and lymphatic invasion [178]. Two major RCTs investigating optimal postoperative therapy for advanced resectable HNSCC have been conducted. The RTOG 9501 trial demonstrated that adjuvant CCRT improved LRC and DFS compared to adjuvant RT alone in patients with multiple LNM (>2), ENE, and microscopic positive margins [172]. Similarly, the EORTC 22931 trial reported that CCRT improved progression-free and OS by reducing locoregional relapse in patients with pT3/pT4 tumors (except T3N0 laryngeal cancer), ENE, positive margins, perineural involvement, or vascular invasion [173]. A comparative analysis of RTOG 9501 and EORTC 22931 concluded that adjuvant CCRT is most beneficial for patients with positive margins or ENE, rather than those with multiple LNM [174,179]. Based on these findings with high-quality evidence, CCRT is recommended post-surgery for patients with ENE, with or without positive margins [178]. Additionally, CCRT may be considered for vascular invasion, perineural invasion, or multiple nodal metastases when its benefits are evident [178].

In summary, postoperative RT or CCRT may be considered for advanced (stage III–IV) laryngeal cancer with multiple nodal metastases, perineural, vascular, or lymphatic invasion; however, CCRT is preferred over RT when positive margins or ENE are present. Given the higher risk of severe adverse events associated with CCRT in HNSCC, patients should be thoroughly informed before proceeding with adjuvant therapy [172,173].

E. Swallowing rehabilitation

E1. What is the role of swallowing rehabilitation in patients with laryngeal cancer?

Recommendation 14

Swallowing rehabilitation may be useful for dysphagia after surgical or nonsurgical treatment for laryngeal cancer. (Conditional recommendation, very low-quality evidence)

Swallowing difficulties are common following both surgical and nonsurgical treatments for laryngeal cancer, often necessitating rehabilitation [180-183]. After partial laryngectomy, aspiration occurs in up to 74% of patients, with recovery typically taking 4–6 weeks; more extensive resections may require a longer recovery period [184-186]. Although supracricoid partial laryngectomy is associated with a high incidence of dysphagia, swallowing function often improves within 3 months post-surgery [183,187]. TL can affect swallowing due to reduced pharyngeal wall contraction and pharyngoesophageal pressure; however, most patients resume a normal diet within 1 month if no complications occur [188]. In addition, RT may cause fibrosis and radionecrosis, impairing tongue and pharyngeal muscle function and leading to dysphagia [189]. Swallowing rehabilitation after laryngeal cancer treatment typically includes posture adjustments, swallowing maneuvers, and bolus modification. Techniques such as the supraglottic, super-supraglottic, Masako, Mendelsohn, and effortful swallowing maneuvers can help reduce aspiration, especially following partial laryngectomy or radiotherapy [180-182,190]. Rehabilitation strategies are tailored based on the extent of structural changes and the severity of dysphagia, often assessed through barium swallow tests.

A systematic literature review identified three studies on swallowing rehabilitation [180-182]. Among them, two prospective studies included head and neck cancer patients in general, rather than focusing specifically on laryngeal cancer, while one retrospective study examined swallowing rehabilitation following supracricoid partial laryngectomy. Due to significant heterogeneity in patient populations, a meta-analysis was not feasible, and a narrative literature review was conducted instead. Lewin et al. [181] found that despite initial severe dysphagia following supracricoid partial laryngectomy, most patients regained oral intake with appropriate rehabilitation strategies. Hajdu et al. [180] reported that swallowing exercises during radiotherapy improved quality of life and functional outcomes, although they did not significantly affect penetration-aspiration scores. Messing et al. [182] indicated that prophylactic swallowing exercises in patients undergoing chemoradiotherapy led to early improvements in oromotor function and swallowing efficiency. These findings suggest that structured swallowing rehabilitation may enhance functional recovery and improve swallowing outcomes in patients with laryngeal cancer.

However, several limitations were noted. Most studies included mixed cohorts of head and neck cancer patients, limiting their applicability specifically to laryngeal cancer. In addition, the retrospective nature of the only laryngeal cancer-specific study further reduced its generalizability. Variability in treatment approaches, rehabilitation protocols, and evaluation time points also contributed to inconsistencies among studies. Given the limited availability of high-quality, controlled studies focused exclusively on laryngeal cancer, the current evidence remains very low in quality, supporting only a conditional recommendation for swallowing rehabilitation. Despite these limitations, the existing data suggest that swallowing rehabilitation may be beneficial for managing dysphagia following surgical or nonsurgical treatment of laryngeal cancer. However, due to differences in dysphagia assessment tools, evaluation time points, and small sample sizes across studies, determining the precise effectiveness of swallowing rehabilitation remains challenging. Nonetheless, the available evidence supports its clinical benefit, highlighting the need for further well-designed, prospective studies to establish more definitive guidelines.

F. Salvage treatment for recurrent laryngeal cancer

F1. What are the salvage treatment options for locally recurrent laryngeal cancer?

Recommendation 15

(A) Total laryngectomy should be considered for most patients with locally recurrent cancer when larynx-preserving strategy is not feasible due to patent and tumor characteristics. (Strong recommendation, low-quality evidence)

(B) Open partial laryngectomy can be considered for selected patients with locally recurrent laryngeal cancer in whom one or two cricoarytenoid units can be preserved. (Conditional recommendation, very low-quality evidence)

(C) Transoral surgery may be considered for well-selected patients with localized and limited recurrent tumors, providing precise preoperative assessment to ensure adequate exposure and complete resectability. (Conditional recommendation, very low-quality evidence)

(D) Radiation therapy/concurrent chemoradiation therapy is an available salvage modality for eligible patients unless it was used in the initial treatment. (Conditional recommendation, very low-quality evidence)

The larynx is generally more amenable to salvage surgery than other head and neck subsites, with salvage total laryngectomy (STL) remaining the primary treatment for locally recurrent, advanced-stage laryngeal cancer. STL is indicated for rT3 tumors associated with cricoarytenoid unit or hemilaryngeal fixation, or extension to the paraglottic/pre-epiglottic spaces, hypopharynx, or subglottis, as well as for rT4a tumors with extralaryngeal spread or cricoid cartilage infiltration [191-194]. STL is also recommended for patients who are poor candidates for laryngeal conservation surgery because of advanced age or compromised cardiopulmonary function—even in cases of smaller tumors [191-194]. Reported 5-year survival rates for STL range from 37.7% to 59% for OS, 54.9% to 68.7% for DSS, and 42.1% to 83% for DFS [191,192,194-196]. However, STL carries a high complication rate, particularly following prior RT with or without chemotherapy. A 2017 systematic review and meta-analysis of 3,292 patients from 50 studies reported an overall complication rate of 67.5%, with pharyngocutaneous fistula being the most common complication, occurring in 5.6% to 73% of cases (pooled incidence, 28.9%) [197].

Open partial laryngectomy has gained acceptance as a salvage option in selected cases, offering acceptable survival outcomes while preserving the larynx. A 2018 meta-analysis by De Virgilio et al. [198], which included 251 patients from 11 studies, reported a 79% 5-year OS, 80% 3-year DFS, 92% 2-year local control, and an 85.2% LPR for salvage supracricoid partial laryngectomy in recurrent laryngeal cancer [198]. Notably, 27.1% of patients had rT3–T4 disease. A 2022 review by Shapira et al. [199], analyzing 323 patients from 15 studies, found a 90.4% laryngectomy-free survival rate after open supracricoid partial laryngectomy, supporting the use of open partial laryngectomy as a viable salvage option following RT failure. Similarly, Lucioni et al. [200] (2016) reported 82% OS, 82% DSS, and a 70% LPR after salvage partial laryngectomy for patients who failed primary transoral laser microsurgery (TLM), suggesting its safety in this setting. However, most studies on salvage open partial laryngectomy are retrospective and involve small patient cohorts (often fewer than 30 patients), which introduces potential selection and publication biases. Surgeons should take these limitations into account when interpreting the favorable outcomes.

TLM is a valuable salvage option for locally recurrent laryngeal cancer, particularly in early-stage recurrence after primary RT/CCRT or TLM. In rT1–T2 disease following RT/CCRT, salvage TLM has demonstrated OS rates ranging from 52.6% to 100.0%, DSS from 67.9% to 100.0%, LCR from 42.0% to 100.0%, and LPR from 63.0% to 100.0% [201-209]. For rT1–T2 disease following primary TLM, reported outcomes include OS of 61.6%–90.0%, DSS of 79.6%–100.0%, LCR of 57.5%–70.2%, and LPR of 38.5%–85.0% [210-213]. A 2023 systematic review and meta-analysis by Russo et al. [214], which included 235 patients undergoing salvage TLM after RT/CCRT and 271 patients after primary TLM, reported pooled 3-year LCR, DSS, and LPR rates of 53.9%, 67.8%, and 73.5% after RT/CCRT, and 53.2%, 77.0%, and 83.7% after primary TLM, respectively. While some studies have explored salvage TLM for rT3-T4a disease, success in these cases depends on strict patient selection, precise preoperative assessment, and significant surgical expertise to ensure adequate exposure and complete resection.

RT/CCRT can also be used as salvage treatment for eligible patients if surgery was used as the primary treatment. However, data on salvage RT/CCRT outcomes after failed first-line surgical treatment remain limited, and its effectiveness for recurrent laryngeal cancer following initial surgery cannot be guaranteed. A 2021 study by Akbaba et al. [215], which included 75 patients who underwent salvage RT/CCRT for recurrent hypopharyngeal and laryngeal cancer after primary surgery alone, reported a 5-year local progression-free survival of 75%, OS of 64%, distant progression-free survival of 82%, and an LPR of 100%.

F2. Does elective neck dissection improve oncological outcomes in salvage treatment for locally recurrent laryngeal cancer?

Recommendation 16

Elective neck dissection can be considered in selected patients with locally recurrent laryngeal cancer who are at high risk for regional recurrence, including those with supraglottic or transglottic involvement and advanced rT category. (Conditional recommendation, very low-quality evidence)

An evaluation was conducted on the rate of occult metastasis in patients with locally recurrent laryngeal cancer who underwent salvage laryngectomy (TL) with prophylactic neck dissection for a clinically N0 neck. The analysis included 22 studies [216-237]. The rate of occult metastasis was assessed in patients who underwent neck dissection; however, a meta-analysis was not feasible, and results were derived through quantitative synthesis. An evaluation was conducted on the rate of occult metastasis in patients with locally recurrent laryngeal cancer who underwent salvage laryngectomy (TL) with prophylactic neck dissection for a clinically N0 neck. The analysis included 22 studies.

Next, a meta-analysis was performed to evaluate DSS rates in relation to neck dissection performed alongside TL. Five studies were included [219,220,227,231,234]. The DSS rate was 64.9% (range, 56.4%–100%) in patients who underwent elective neck dissection, compared to 70.5% (range, 54.6%–100%) in those who did not. The meta-analysis found no significant difference in DSS between the two groups (RR, 0.96; 95% CI, 0.78–1.19), likely due to variations in patient numbers, primary tumor sites (supraglottic, transglottic, glottic), disease stage, and evaluation time points. Furthermore, a meta-analysis of OS rates was conducted using data from eight studies [217-220,227,231,236,237]. The OS rate was 62.9% (range, 42.9%–100%) in patients who underwent elective neck dissection, compared to 60.4% (range, 36.2%–100%) in those who did not. No significant difference in OS was found between the two groups (RR, 1.01; 95% CI, 0.86–1.17). A meta-analysis of regional recurrence rates was conducted using data from nine studies [216-219,223,226,233,234,237]. The regional recurrence rate was 7.7% (range, 0%–18.8%) in patients who underwent elective neck dissection, compared to 9.2% (range, 0%–30.8%) in those who did not. This meta-analysis also found no significant difference in regional recurrence rates between the two groups (RR, 0.69; 95% CI, 0.40–1.21).

An assessment of complications associated with neck dissection performed alongside TL was also conducted. Commonly evaluated complications included pharyngocutaneous fistula, wound hematoma, and infection. Some studies additionally assessed chyle leakage and prolonged feeding tube use. Despite variations in complication types and assessment timings across studies [216-218,220,222,223,231,233,237], the meta-analysis revealed no significant difference in complication rates between groups with and without neck dissection (RR, 1.25; 95% CI, 0.84–1.87).

Two papers included in the systematic review reported differences in occult metastasis rates and corresponding survival rates based on the primary tumor site. Birkeland et al. (2016) [225] found a higher occult metastasis rate of 28% in the supraglottis compared to other subsites (P<0.00). Koss et al. [227] reported occult metastasis rates of 60% in the supraglottis (P=0.02) and 30% in the transglottis, with correspondingly lower survival rates (P=0.02). Birkeland et al. [225] also reported that higher primary tumor stages at recurrence were associated with increased occult metastasis rates: 10% for T1–T2, 15.7% for T3, and 34% for T4 (P<0.00). Most studies in this review focused on cases where initial treatment involved RT or chemoradiotherapy. Further evaluation is needed to determine the applicability of these findings to cases where surgical management was the primary treatment.

Concluding remarks

The management of laryngeal cancer requires a careful balance between achieving optimal oncologic outcomes and preserving essential functions such as voice and swallowing. The Korean Society of Head and Neck Surgery, with support from the KCGN, has developed new guidelines for laryngeal cancer management. A key limitation of these guidelines is the lack of active involvement by a multidisciplinary committee during the development process, underscoring the need for future revisions that incorporate broader expertise. Additionally, most key recommendations are based on low-quality evidence and are conditional in nature, making it difficult to provide a clear decision flow. This limitation should be addressed by generating high-quality evidence through future research. Nevertheless, these guidelines—developed through systematic literature review, meta-analysis, and expert consensus, with methodological consultation based on GRADE criteria—offer evidence-based recommendations intended to assist clinicians in making informed treatment decisions.

HIGHLIGHTS

▪ The guidelines provide comprehensive, evidence-based recommendations for laryngeal cancer management, developed through a systematic literature review, meta-analysis, and expert consensus.

▪ In addition to prioritizing oncologic control, the guidelines emphasize preserving essential functions such as voice and swallowing, and favor organ‐preserving strategies when feasible.

▪ The recommendations are tailored to disease stage, patient condition, and treatment goals to achieve optimal outcomes.

SUPPLEMENTARY MATERIALS

Supplementary materials can be found online at https://doi.org/10.21053/ceo.2025.00009.

Supplementary Material 1.

The search string used for each key question.

Supplementary Material 2.

Flow diagram of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Supplementary Material 3.

Quality assessment of the included studies.

Supplementary Material 4.

Guidelines for the treatment of laryngeal cancer from the Korean Society of Head and Neck Surgery.