ONCOLOGICAL AND FUNCTIONAL OUTCOMES FOLLOWING TRANSORAL CO₂ LASER SURGERY FOR EARLY-STAGE LARYNGEAL CANCER

Summary

Methods: Sixty-two patients with histopathologically confirmed early-stage laryngeal squamous cell carcinoma who underwent transoral CO₂ laser surgery between 2000 and 2010 were retrospectively reviewed. Oncological outcomes, recurrence patterns, clinically assessed functional outcomes, organ preservation, and survival were analyzed. Survival analyses were performed using the Kaplan–Meier method, where appropriate.

Results: The median follow-up period was 24 months (mean, 25.9 months; range, 3–89 months). Seven patients (11.3%) developed recurrence, including five local recurrences and two isolated cervical nodal recurrences. Clinical functional outcomes were favorable, with permanent tracheotomy and gastrostomy observed in three patients each (4.8%). Salvage total laryngectomy was performed in five patients. The overall organ preservation rate was 91.9%, while the overall survival and disease-specific survival rates were 91.9% and 96.8%, respectively. Kaplan–Meier survival analysis demonstrated significantly better overall survival among patients with glottic carcinoma than among those with supraglottic carcinoma (95.9% vs. 76.9%; log-rank p = 0.017).

Conclusion: Transoral CO₂ laser surgery provides favorable oncological outcomes together with satisfactory clinical functional outcomes in appropriately selected patients with early-stage laryngeal carcinoma. The high organ preservation rate and encouraging survival outcomes observed in this series support TLS as an effective organ-preserving treatment modality. This study represents one of the earliest comprehensive single-center experiences from Türkiye reporting both oncological and clinically assessed functional outcomes following transoral CO₂ laser surgery for early-stage laryngeal carcinoma.

Introduction

Radiotherapy and surgery are the two principal treatment modalities for T1–T2 laryngeal carcinoma [1,3]

[5-10]. Among surgical approaches, transoral CO₂ laser surgery (TLS) has gained widespread acceptance because it enables precise tumor resection with excellent visualization, minimal thermal damage, effective hemostasis, shorter hospitalization, rapid postoperative recovery, and favorable functional outcomes [1,2,6-11]. In the present study, functional outcomes refer to clinically assessed laryngeal preservation, airway status, swallowing ability, and enteral feeding requirement rather than standardized patient-reported outcome measures. An additional advantage of TLS is the preservation of future treatment options, allowing repeat transoral surgery or radiotherapy in the event of local recurrence without compromising subsequent oncological management.

Numerous studies have demonstrated that TLS provides local control and survival rates comparable to those of radiotherapy while maintaining high rates of laryngeal preservation [2,6-12]. Recent systematic reviews and meta-analyses have further confirmed that, in appropriately selected patients, TLS offers oncological outcomes equivalent to radiotherapy together with advantages such as shorter treatment duration, reduced treatment burden, and the possibility of repeated endoscopic treatment for recurrent disease ^[9,13]. Nevertheless, interpretation of historical and contemporary series requires caution because substantial advances in laser technology, endoscopic imaging, perioperative management, and patient selection have occurred over the past two decades.

Although several studies from Türkiye have evaluated transoral laser surgery for laryngeal cancer, comprehensive national data remain relatively limited.

Doluoglu et al. demonstrated oncological outcomes comparable with radiotherapy in a large Turkish cohort of patients with early-stage laryngeal carcinoma, whereas Baklacı et al. reported favorable local control and low complication rates following transoral laser microsurgery for early glottic carcinoma [14,15].

Gökmen et al. likewise demonstrated satisfactory oncological and functional outcomes in patients treated with transoral laser surgery for supraglottic carcinoma [7]. However, studies simultaneously evaluating oncological and functional outcomes in Turkish patients remain scarce.

Therefore, the present study aimed to evaluate the oncological and functional outcomes of transoral CO₂ laser surgery in patients with early-stage laryngeal carcinoma treated at a tertiary referral center.

In addition to reporting survival, local control, and organ preservation, this study represents one of the earliest comprehensive single-center Turkish experiences with transoral CO₂ laser surgery. We also sought to present the surgical strategy adopted in our institution, including standardized intraoperative frozen-section assessment, systematic surgical margin management, and specimen orientation, all of which contributed to individualized surgical decision-making and long-term patient follow-up.

Methods

During the study period, 79 consecutive patients underwent TLS. Sixty-two patients with complete clinical records, histopathological confirmation of squamous cell carcinoma, and adequate follow-up data were included in the final analysis. Patients with incomplete medical records, previous treatment for laryngeal carcinoma, synchronous head and neck malignancies, or insufficient follow-up were excluded.

Preoperative Evaluation
All patients underwent a comprehensive head and neck examination, including indirect or fiberoptic laryngoscopy, direct laryngoscopy under general anesthesia, and contrast-enhanced cervical computed tomography when indicated. Magnetic resonance imaging was performed selectively when cartilage invasion or deep paraglottic extension was suspected.

Tumor localization, T stage, anterior commissure involvement, vocal cord mobility, subglottic extension, and cervical lymph node status were assessed preoperatively. The indication for transoral CO₂ laser surgery was determined according to tumor characteristics, adequacy of endoscopic exposure, and the patient’s general medical condition.

Surgical Technique
All surgical procedures were performed under general anesthesia using suspension microlaryngoscopy and a Carl Zeiss operating microscope (Carl Zeiss, Oberkochen, West Germany) coupled with a Compact 30C CO₂ laser system (Lumenis™, Israel). The laser was operated in continuous SuperPulse mode with a power setting of 5 W.

The extent of resection was determined according to tumor localization, depth of invasion, and intraoperative findings. Whenever technically feasible, en bloc tumor resection was preferred. In lesions requiring wider exposure or involving multiple anatomical subsites, stepwise resection was performed while maintaining strict oncological principles. Particular attention was paid to achieving adequate surgical margins while preserving uninvolved laryngeal structures and postoperative laryngeal function.

Intraoperative Margin Assessment
Intraoperative frozen-section analysis was routinely performed in all patients. Whenever frozen-section examination demonstrated tumor involvement, additional resection was immediately performed until tumor-free frozen-section margins were achieved. When surgical resection reached anatomical structures devoid of residual soft tissue, including the inner perichondrium of the thyroid cartilage or the arytenoid cartilage, these anatomical boundaries were accepted as definitive negative margins because no additional tissue remained for further excision.

The resected specimens were carefully oriented and pinned onto cardboard to preserve their anatomical orientation. Surgical margins were identified using different tissue dyes according to anatomical direction before submission for permanent histopathological examination. In addition, the extent of each resection was documented using standardized schematic drawings (marking forms), which were incorporated into the patients’ medical records (Figure 1). All frozen-section and permanent histopathological evaluations were performed by dedicated head and neck pathologists.

Figure 1: Marking form of one of the patients. For adequate exposure, both ventricular bands were partially resected. The left glottic tumor was excised with clear surgical margins through the thyroid cartilage perichondrium, including a portion of the right vocal cord and the paraglottic space.

Whenever permanent histopathological examination raised concern regarding margin status, frozen-section findings were re-evaluated together with the operative drawings and pathological orientation. Operative video recordings were reviewed whenever necessary to facilitate accurate correlation between surgical orientation and histopathological findings. If negative frozen sections and reliable anatomical barriers confirmed complete tumor excision, patients were managed with close clinical surveillance (Figure 2). When uncertainty regarding residual disease persisted, repeat direct laryngoscopy with frozen-section analysis and biopsy was performed, followed by additional transoral CO₂ laser resection until tumor-free margins were achieved.

Figure 2: Transoral laser en bloc excision of the tumor located at the epiglottic petiole and postoperative appearance of the remaining tissue, demonstrating the inner lamina of the thyroid cartilage and the vocal cords.

Neck Management
Neck management was individualized according to tumor location and nodal status. Elective selective neck dissection (levels II–IV) was routinely performed in all patients with supraglottic carcinoma. In contrast, patients with glottic carcinoma underwent therapeutic neck dissection (levels II–IV) only when clinically or radiologically evident cervical lymph node metastasis was present.

Postoperative Management and Follow-up
Postoperative management was standardized for all patients. Systemic corticosteroids were administered in cases of significant postoperative airway edema.

Oral intake was initiated as early as tolerated, and enteral feeding was provided when necessary, particularly in patients undergoing supraglottic resections.

Adjuvant radiotherapy was administered to patients with adverse pathological features according to the multidisciplinary tumor board recommendations.

Patients were subsequently followed regularly in the outpatient clinic. Follow-up visits were scheduled monthly during the first postoperative year, every two months during the second year, every three months during the third year, every six months until the fifth postoperative year, and annually thereafter. Each visit included endoscopic examination, while radiological imaging was performed whenever local recurrence or regional metastasis was suspected. The follow-up period ranged from 3 to 89 months. Both mean and median follow-up durations were calculated to better characterize the heterogeneous follow-up period.

Functional outcomes were assessed using clinical parameters, including tracheostomy dependence, swallowing status, enteral feeding requirement, and laryngeal preservation, as standardized patient-reported outcome measures were not routinely available during the study period.

Statistical Analysis
Statistical analyses were performed using SPSS for Windows, version 15.0 (SPSS Inc., Chicago, IL, USA). Continuous variables were expressed as mean ± standard deviation or median (range), whereas categorical variables were summarized as frequencies and percentages and compared using Pearson’s chi-square test or Fisher’s exact test, as appropriate. The follow-up period was summarized using both mean and median values. Overall survival and disease-specific survival were estimated using the Kaplan–Meier method, and differences between survival curves were compared using the log-rank test. A two-sided p value of <0.05 was considered statistically significant.

Results

Table 1: Baseline Demographic and Clinical Characteristics of the Study Population

Tumor Characteristics
Tumor characteristics are presented in Table 2.

Glottic carcinoma was the predominant tumor site (79.0%), whereas the remaining patients had supraglottic carcinoma (21.0%). According to the TNM classification, 44 patients were diagnosed with T1 disease and 17 patients with T2 disease. One patient initially staged as cT2 supraglottic carcinoma was pathologically upstaged to pT4 because of epiglottic cartilage invasion identified on permanent histopathological examination[16]. Cervical lymph node metastasis at presentation was identified exclusively in patients with supraglottic carcinoma.

Table 2: Tumor Characteristics

Surgical Outcomes
All patients underwent transoral CO₂ laser surgery as the primary treatment modality. The extent of resection was determined according to tumor localization and intraoperative findings. Whenever technically feasible, en bloc tumor resection was performed.

Intraoperative frozen-section analysis was routinely used to guide surgical margin assessment. Initial permanent histopathological examination demonstrated suspicious surgical margins in 22 patients (35.5%).

Correlation of frozen-section findings with specimen orientation, standardized marking forms, operative video documentation, and permanent histopathological evaluation enabled accurate reassessment of margin status. Based on this comprehensive multidisciplinary evaluation, five patients (8.1%) underwent repeat transoral CO₂ laser surgery, and tumor-free surgical margins were ultimately achieved in all reoperated cases. Four patients (6.5%) received adjuvant radiotherapy because of adverse pathological features, including cervical nodal metastasis or suspected thyroid cartilage invasion. The remaining 13 patients (21.0%) were managed with close clinical follow-up because the combined assessment confirmed adequate surgical margins despite suspicious permanent histopathological findings.

Functional Outcomes
Functional outcomes are summarized in Table 3. Temporary swallowing impairment occurred predominantly in patients undergoing supraglottic resections and resolved during follow-up. Long-term enteral feeding and permanent tracheostomy were uncommon. Overall, laryngeal preservation was achieved in 57 of 62 patients (91.9%), demonstrating satisfactory functional preservation following transoral CO₂ laser surgery.

Table 3: Functional Outcomes

Recurrence and Survival Outcomes
Oncological and functional outcomes are summarized in Table 3. During a median follow-up period of 24 months (mean, 25.9 months; range, 3–89 months), seven patients (11.3%) developed recurrence, including five local recurrences and two isolated cervical nodal recurrences. All nodal recurrences occurred in patients with supraglottic carcinoma. Salvage total laryngectomy was required in five patients, including two with glottic carcinoma and three with supraglottic carcinoma. The overall organ preservation rate was 91.9%, while overall survival and disease-specific survival were 91.9% and 96.8%, respectively. Kaplan–Meier survival analysis demonstrated significantly better overall survival among patients with glottic carcinoma than among those with supraglottic carcinoma (95.9% vs. 76.9%; log-rank p = 0.017) (Figure 3).

Discussion

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Figure 3: Overall survival rates according to tumor localization. Overall survival was 95.9% in patients with glottic tumors and 76.9% in patients with supraglottic tumors (p = 0.017).

The demographic characteristics of our cohort are consistent with the well-established epidemiology of laryngeal squamous cell carcinoma. The marked predominance of male patients and the high prevalence of tobacco exposure are comparable with those reported in previous Turkish and international studies.

Likewise, the predominance of glottic tumors reflects the earlier onset of symptoms, particularly persistent dysphonia, facilitating earlier diagnosis than supraglottic carcinoma[5,10,22].

One of the most clinically relevant findings of the present study is the high organ preservation rate. Preservation of laryngeal function has become one of the principal treatment goals in early-stage laryngeal cancer because voice quality, swallowing, and airway protection directly influence patients’ quality of life. In our series, laryngeal preservation was achieved in 57 of 62 patients (91.9%), while only five patients required salvage total laryngectomy because of recurrent disease. These findings are consistent with the pioneering work of Steiner and the subsequent studies by Ambrosch and Peretti, which demonstrated that transoral laser microsurgery can achieve durable oncological control while avoiding total laryngectomy in the majority of appropriately selected patients [17,22-25].

Our oncological outcomes are also consistent with contemporary international literature. Campo et al.

reported local control and survival rates comparable with those of radiotherapy and open partial laryngectomy in selected patients with T2 laryngeal carcinoma[6]. Likewise, Elicin and Giger concluded that transoral laser microsurgery provides oncological outcomes equivalent to radiotherapy while preserving future treatment options [10]. More recently, Yang et al. demonstrated in a meta-analysis that transoral CO₂ laser microsurgery provides survival outcomes comparable with radiotherapy while offering advantages such as shorter treatment duration, treatment repeatability, and high organ preservation rates [9].

Collectively, these findings further support TLS as a standard organ-preserving treatment modality for carefully selected patients with early-stage laryngeal carcinoma.

Our findings are also consistent with recently published Turkish studies. Doluoglu et al. demonstrated disease-free survival rates comparable with those of radiotherapy and confirmed the oncological safety of transoral laser surgery in early-stage laryngeal carcinoma[15]. Similarly, Baklacı et al. reported favorable oncological outcomes with low complication and recurrence rates following transoral laser microsurgery in patients with early glottic carcinoma[14]. Gökmen et al. likewise demonstrated satisfactory oncological and functional outcomes following transoral laser surgery for supraglottic carcinoma[7]. The present study complements these reports by representing one of the earliest comprehensive single-center Turkish experiences evaluating both oncological and functional outcomes following transoral CO₂ laser surgery.

During follow-up, seven patients (11.3%) developed recurrence, including five local recurrences and two isolated cervical nodal recurrences. Notably, all nodal recurrences occurred in patients with supraglottic carcinoma. This observation is consistent with the richer lymphatic drainage and the greater propensity for cervical metastasis associated with the supraglottic larynx. Although the number of nodal recurrences was small, these findings emphasize the importance of careful preoperative neck assessment and meticulous postoperative surveillance in patients with supraglottic tumors [26].

One of the distinctive features of the present study is the standardized intraoperative surgical strategy used for surgical margin assessment. Frozen-section analysis was routinely performed in all patients, and additional resection was carried out whenever tumor involvement was detected until negative frozen-section margins were achieved. Resected specimens were systematically oriented using color-coded surgical margins, documented with standardized marking forms, and correlated with permanent histopathological findings. Whenever permanent pathology raised concern regarding residual disease, frozen-section findings and operative drawings were reviewed before deciding between close observation and repeat transoral laser surgery. This standardized workflow allowed individualized surgical decision-making and contributed to reliable surgical margin assessment.

The present study reflects the early implementation period of transoral CO₂ laser surgery at our institution. Surgical procedures were performed using a Compact 30C CO₂ laser system (Lumenis™, Israel) operating in SuperPulse mode (5 W) under a Carl Zeiss operating microscope (Carl Zeiss, Oberkochen, West Germany). Considerable advances in laser technology, optical systems, imaging quality, and perioperative management have occurred over the past two decades. Furthermore, diode and blue laser systems have recently been introduced into transoral laryngeal surgery. Therefore, direct comparison between historical and contemporary series should be interpreted cautiously. Nevertheless, available evidence suggests that, when sound oncological principles are respected, different laser platforms provide comparable oncological and functional outcomes. Consequently, surgical expertise, meticulous patient selection, and standardized surgical technique are likely to have a greater influence on treatment outcomes than the specific laser platform itself.

It is noteworthy that one patient who was clinically staged as T2 supraglottic carcinoma was pathologically upstaged to pT4 because of unsuspected epiglottic cartilage invasion identified on permanent histopathological examination. As treatment decisions were based on the preoperative clinical stage, this patient was retained in the analysis. This observation illustrates the inherent limitations of clinical staging and highlights that pathological upstaging remains an unavoidable aspect of surgical management in laryngeal carcinoma. Nevertheless, inclusion of this patient reflects real-world clinical practice, in which treatment decisions are necessarily based on preoperative clinical rather than postoperative pathological staging. This approach minimizes selection bias and more accurately reflects routine clinical decision-making.

Strengths and Limitations
The present study has several important strengths.

It represents one of the earliest comprehensive single-center Turkish experiences reporting both oncological and clinically assessed functional outcomes following transoral CO₂ laser surgery. All procedures were performed by the same experienced surgical team using a standardized treatment protocol. An additional strength of the present study is the standardized multidisciplinary workflow involving experienced head and neck surgeons and dedicated head and neck pathologists, which ensured consistent intraoperative margin assessment, accurate surgical decision-making, and reliable clinicopathological correlation. Furthermore, the routine use of frozen-section analysis, specimen orientation with color-coded margin mapping, standardized marking forms, and correlation with permanent histopathological findings enhanced the methodological reliability of the study.

Several limitations should also be acknowledged.

First, glottic and supraglottic carcinomas were evaluated within the same study cohort. Although both represent early-stage laryngeal carcinoma, they differ considerably in biological behavior, lymphatic drainage, recurrence patterns, and prognosis, introducing a degree of heterogeneity into the study population.

Second, although anterior commissure involvement, impaired vocal cord mobility, and subglottic extension were recorded, their effects on local recurrence could not be evaluated statistically because fewer than five patients were represented in each subgroup.

Likewise, the effects of anterior commissure involvement, vocal cord mobility impairment, subglottic extension, local recurrence, surgical margin status, and cervical lymph node metastasis on overall survival could not be analyzed because the number of events within each subgroup was insufficient for meaningful statistical evaluation. Third, the retrospective single-center design inherently limits control of potential confounding variables. Finally, functional outcomes were assessed using clinical parameters, including tracheostomy dependence, enteral feeding requirement, swallowing status, and laryngeal preservation, rather than validated patient-reported voice- or swallowing-related outcome measures such as the Voice Handicap Index (VHI), MD Anderson Dysphagia Inventory (MDADI), or EAT-10. This reflects both the retrospective nature of the study and the historical period during which these patients were treated. In addition, although the median follow-up period was 24 months (range, 3–89 months), the heterogeneous follow-up duration and the limited number of survival events should be considered when interpreting the survival analyses. Future prospective studies incorporating standardized functional outcome measures together with longer and more homogeneous follow-up are warranted to provide a more comprehensive assessment of oncological and functional outcomes.

Clinical Implications
The present findings have several important clinical implications. In appropriately selected patients, transoral CO₂ laser surgery provides favorable oncological outcomes while preserving clinically assessed laryngeal function and maintaining future treatment options. Moreover, a standardized surgical strategy incorporating routine intraoperative frozen-section analysis, systematic specimen orientation, color-coded margin mapping, and multidisciplinary clinicopathological correlation may improve surgical margin assessment, facilitate individualized intraoperative and postoperative decision-making, and potentially reduce unnecessary additional treatment.

Future Perspectives
Future prospective multicenter studies involving larger patient cohorts, longer and more homogeneous follow-up, validated patient-reported voice- and swallowing-related outcome measures, and contemporary laser technologies are warranted to further define prognostic factors influencing both oncological and functional outcomes following transoral CO₂ laser surgery. Future studies should also evaluate whether standardized intraoperative margin management protocols can improve both oncological safety and functional preservation across different institutions.

Conclusion

In the present series, overall survival, disease-specific survival, and organ preservation rates were 91.9%, 96.8%, and 91.9%, respectively.

Beyond these clinical outcomes, the present study highlights the importance of a standardized multidisciplinary surgical strategy incorporating routine intraoperative frozen-section analysis, meticulous surgical margin management, specimen orientation using color-coded margin mapping, and close collaboration between experienced head and neck surgeons and dedicated head and neck pathologists. This structured workflow contributed to accurate surgical decision-making, reliable clinicopathological correlation, and individualized postoperative management.

Although this study reflects an early institutional experience with first-generation CO₂ laser technology, the observed oncological and clinically assessed functional outcomes are consistent with those reported in both contemporary Turkish and international series. Future prospective multicenter studies including larger patient cohorts, longer follow-up, validated functional outcome measures, and contemporary laser technologies are warranted to further optimize patient selection and refine prognostic factors.

Take-home message
Careful patient selection, meticulous intraoperative margin assessment, and a standardized multidisciplinary surgical–pathological workflow remain the key determinants of successful oncological control, clinically assessed functional preservation, and organ preservation following transoral CO₂ laser surgery for early-stage laryngeal carcinoma.

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