What are the treatment strategies to preserve the larynx in patients with locally advanced carcinoma of the larynx?

Treatment Strategies for Larynx Preservation in Locally Advanced Laryngeal Carcinoma

Primary Treatment Recommendation

For patients with locally advanced (T3, T4a) laryngeal carcinoma who have good pretreatment laryngeal function and no cartilage penetration, concurrent cisplatin-based chemoradiation is the standard of care, offering superior locoregional control (78% at 2 years) and larynx preservation (88% at 2 years) compared to radiation alone or induction chemotherapy followed by radiation. 1, 2

Patient Selection: Critical First Step

Before selecting any larynx-preservation strategy, you must identify appropriate candidates versus those requiring primary total laryngectomy:

Ideal candidates for organ preservation: 1, 3

• T2N+, T3, and limited T4a tumors meeting RTOG 91-11 eligibility criteria
• Good pretreatment laryngeal function (functional larynx)
• Absence of extensive cartilage destruction or tumor penetration through cartilage into soft tissues

Poor candidates requiring primary total laryngectomy: 4, 3

• Extensive T3 or large T4a lesions
• Nonfunctional larynx at presentation
• Tumor penetration through cartilage into surrounding soft tissues
• Severe pretreatment laryngeal dysfunction

This distinction is critical because poorly selected patients have greater risk of treatment failure and decreased survival with organ preservation approaches. 1

Standard Concurrent Chemoradiation Protocol

Chemotherapy regimen: 1, 2

• High-dose cisplatin 100 mg/m² every 3 weeks is the only radiosensitizing agent supported by evidence
• This is superior to induction chemotherapy followed by radiation (75% larynx preservation) or radiation alone (70% larynx preservation) 2

Radiation technique: 1

• Modern three-dimensional conformal or IMRT planning
• Once-daily fractionation (avoid twice-daily fractionation due to significantly increased severe late dysphagia risk)
• Standard dosing per institutional protocols

Alternative Organ-Preservation Options

Induction chemotherapy followed by radiation: 5, 6

• Cisplatin plus fluorouracil for 2-3 cycles, followed by definitive radiation (6600-7600 cGy) for responders
• Achieves 68% 2-year survival with 64% larynx preservation in responders 5
• Inferior locoregional control (61%) compared to concurrent chemoradiation (78%) 2
• Consider for patients who cannot tolerate concurrent therapy

Radiation therapy alone: 3, 2

• Appropriate for patients who desire larynx preservation but are not candidates for chemotherapy
• Achieves similar survival to chemoradiation when salvage surgery is incorporated, but lower likelihood of larynx preservation (70% vs 88%) 2
• Requires close surveillance for early detection of recurrence amenable to salvage surgery

Expected Outcomes and Survival

With concurrent chemoradiation: 1, 7

• 3-year larynx preservation with local disease control: 83%
• 5-year larynx preservation with local disease control: 77%
• 5-year overall survival: 45-67%
• Stage-specific 5-year survival: Stage III 58.9%, Stage IVa 34.9%, Stage IVb 30.4% 7

Critical point: No larynx-preservation approach offers a survival advantage compared with total laryngectomy and appropriate adjuvant treatment—patients must understand this during treatment planning. 4, 3

Management of Regional Nodes

For N+ disease after chemoradiation: 3

• Patients with complete clinical and radiologic imaging response do not require elective neck dissection
• N2 or N3 disease requires surgical treatment of the neck regardless of response, as salvage surgery for recurrent neck disease is rarely successful 3

Mandatory Pretreatment Evaluation

All patients require: 3, 4

• Baseline assessment of voice and swallowing function
• Multidisciplinary team evaluation
• Counseling regarding potential impact of treatment options on voice, swallowing, and quality of life
• Enrollment in mandatory smoking cessation programs (continued smoking associated with worse outcomes) 1, 4

Critical Pitfalls to Avoid

Do not combine surgery with radiation for limited disease: 4

• Single-modality treatment is mandatory for T1-T2 disease
• Combining modalities compromises functional outcomes without survival benefit

Do not plan surgery anticipating positive margins: 3

• Surgery with anticipated need for postoperative radiation to treat close/involved margins is unacceptable
• Adequate margins are 4-5 mm for open resections, ≥2 mm for endoscopic resections 3

Avoid twice-daily radiation fractionation: 1

• 5-year cumulative incidence of severe late dysphagia is 26.5% with standard fractionation
• Twice-daily fractionation significantly increases this risk

Do not use induction chemotherapy before concurrent chemoradiation: 3

• Insufficient evidence that adding induction before concurrent treatment improves survival or larynx preservation

Salvage Surgery for Treatment Failures

For local recurrence after radiation/chemoradiation: 3

• Close surveillance detects early recurrence amenable to salvage
• Salvage may be achieved with endoscopic or open larynx-preserving surgery when detected early
• Total laryngectomy required for substantial proportion of patients, especially those with index T2 tumors 3
• Success of salvage surgery depends on early detection through close follow-up