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

Non-Surgical Treatment Strategies for Larynx Preservation in Locally Advanced Laryngeal Carcinoma

Concurrent cisplatin-based chemoradiation is the standard of care for larynx preservation in patients with intermediate- and advanced-stage (T2N+, T3, and limited T4) operable laryngeal cancer, offering superior locoregional control and larynx preservation compared to radiation alone or induction chemotherapy followed by radiation. 1

Patient Selection: Critical Determinant of Success

Proper patient selection is the most critical factor determining whether larynx preservation will succeed without compromising survival. 1

Ideal Candidates for Non-Surgical Larynx Preservation:

• T2N+, T3, and limited T4a tumors meeting RTOG 91-11 eligibility criteria 1
• Good pre-treatment laryngeal function with adequate voice and swallowing capacity 1, 2
• Absence of extensive cartilage destruction or tumor penetration through cartilage into surrounding soft tissues 1, 3
• Willingness and ability to participate in close follow-up for early salvage surgery if needed 1, 2

Poor Candidates Requiring Primary Total Laryngectomy:

• Extensive T3 or large T4a lesions with poor pretreatment laryngeal function achieve better survival and quality of life with total laryngectomy rather than organ preservation. 1, 3
• T4 tumors with extensive cartilage destruction or deep invasion into tongue musculature 1
• Nonfunctional larynx at baseline 3
• High-volume T4 cancers with tumor penetration through cartilage 1, 3

Standard Treatment Approach: Concurrent Chemoradiation

Preferred Regimen:

• High-dose cisplatin (100 mg/m² every 3 weeks) concurrent with radiation therapy is the only radiosensitizing agent supported by evidence. 1
• Radiation delivered using modern three-dimensional conformal or IMRT planning with once-daily fractionation 1
• Carboplatin substitution is acceptable only when cisplatin is contraindicated 1

Evidence Supporting Concurrent Approach:

• Concurrent cisplatin and RT demonstrates clear advantage over induction chemotherapy followed by RT when assessing individual endpoints of larynx preservation and locoregional control 1
• Both induction cisplatin plus 5-FU and concurrent cisplatin-RT are more effective than RT alone using the composite endpoint of laryngectomy-free survival 1
• The RTOG 91-11 trial and subsequent updates continue to support concurrent cisplatin-RT as the preferred standard of care 1

Expected Outcomes with Concurrent Chemoradiation:

• 3-year larynx preservation with local disease control: 83% 1
• 5-year larynx preservation with local disease control: 77% 1
• 5-year overall survival: 45-67% 1, 3

Alternative Approach: Induction Chemotherapy Followed by Definitive Treatment

When to Consider Induction:

• Induction chemotherapy serves as a predictive biomarker for successful organ preservation based on response 1
• The induction approach is favored in Europe based on EORTC and GORTEC trials 1
• Acceptable for T2N+ and T3 tumors when concurrent chemoradiation is not feasible 2

Induction Regimen Options:

• Cisplatin plus 5-FU (standard) 1
• Cisplatin, 5-FU, and docetaxel (taxane addition supported by GORTEC trial with higher response rates) 1

Critical Limitation:

• Insufficient evidence indicates that adding induction chemotherapy before concurrent treatment improves survival or larynx-preservation outcomes compared to concurrent chemoradiation alone. 1

Radiation Therapy Alone

• RT alone is less effective than combined-modality approaches for larynx preservation 1
• Reserved for patients medically unfit for chemotherapy 3, 4
• Not recommended as primary treatment when patient can tolerate concurrent chemotherapy 1

Management of Late Toxicity and Quality of Life

Dysphagia: The Major Late Complication:

• 5-year cumulative incidence of severe late dysphagia is substantial at 26.5% (95% CI, 15.2-37.8%) following concurrent chemoradiation. 1
• Twice-daily fractionation significantly increases severe late dysphagia risk and should be avoided 1
• Modern IMRT planning and proactive swallowing therapy programs reduce late-occurring dysphagia compared to two-dimensional planning 1
• 18% of patients with late dysphagia experience first event beyond 5 years, requiring long-term surveillance 1

Functional Outcomes:

• 5% require pharyngeal dilations 1
• 3% require permanent gastrostomy feeding 1
• No deaths directly attributable to severe dysphagia despite high incidence 1

Critical Pitfalls to Avoid

Treatment Selection Errors:

• Poorly selected patients (tumors more advanced than RTOG 91-11 eligibility) have greater risk of treatment failure and decreased survival with organ preservation approaches. 1
• Continued cigarette smoking is associated with worse outcomes; mandatory enrollment in cessation programs 3

Mandatory Multidisciplinary Evaluation:

• Pre-treatment speech and swallowing assessment is critically important for determining candidacy 1, 3
• Assessment must include age, comorbidities, preferences, socioeconomic factors, and availability of rehabilitation services 1, 3
• No larynx-preservation approach offers survival advantage compared to total laryngectomy with appropriate adjuvant treatment; patients must understand this during treatment planning. 3

Follow-Up Requirements:

• Active surveillance to ensure early salvage laryngectomy for treatment failures is essential 1, 2
• Failure to detect early recurrence compromises survival outcomes 1, 2

Treatment Algorithm Summary

For T2N+, T3, and limited T4a with good baseline laryngeal function:

• First-line: Concurrent cisplatin (100 mg/m² q3weeks) with once-daily RT using IMRT planning 1
• Alternative: Induction cisplatin/5-FU/docetaxel followed by concurrent chemoradiation or RT based on response 1
• Salvage: Total laryngectomy for treatment failures with close surveillance 1, 2

For extensive T3, large T4a, or poor baseline laryngeal function:

• Primary total laryngectomy with appropriate adjuvant therapy 1, 3

For cisplatin-ineligible patients:

• Carboplatin-based concurrent chemoradiation 1
• RT alone if chemotherapy contraindicated 3, 4