Survival Differences Between DRT and S+RT in Supraglottic & Hypopharyngeal Carcinoma

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Survival Differences Between Definitive Radiotherapy and Surgery Followed by Adjuvant Radiotherapy in Supraglottic and Hypopharyngeal Carcinoma

Introduction

Supraglottic and hypopharyngeal carcinomas are aggressive malignancies of the head and neck, often presenting with symptoms such as voice changes, swallowing difficulties, and airway obstruction. The primary goals of treatment include optimizing survival while preserving organ function and quality of life (QOL). Traditional treatment options include definitive radiotherapy (DRT) with or without systemic therapy (chemotherapy or targeted agents) and surgery followed by adjuvant radiotherapy (S+RT). Total laryngectomy or extensive hypopharyngectomy can lead to significant functional impairments, making DRT an attractive option for organ preservation.

The advent of intensity-modulated radiotherapy (IMRT) has improved tumor targeting while minimizing damage to surrounding tissues, potentially enhancing therapeutic outcomes. This retrospective study aimed to compare survival outcomes, including overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS), between patients undergoing DRT and those treated with S+RT for supraglottic and hypopharyngeal carcinomas.

Methods

Patient Population

The study included 59 adult patients diagnosed with supraglottic (24 cases) or hypopharyngeal (35 cases) carcinoma between January 2012 and August 2016 at Peking University First Hospital. All patients had biopsy-confirmed squamous cell carcinoma, except one case of carcinosarcoma. Staging followed the AJCC/UICC 7th edition system: 6.8% (n=4) had stage I, 22% (n=13) stage II, 20.3% (n=12) stage III, and 50.8% (n=30) stage IV disease. Patients were divided into two cohorts:

  • DRT Group: 31 patients treated with definitive radiotherapy.
  • S+RT Group: 28 patients treated with surgery followed by adjuvant radiotherapy.

Baseline characteristics, including age, gender, tumor stage, nodal involvement, and histological grade, were balanced between the groups (Table 1).

Treatment Protocols

DRT Group:

  • 23 patients received concurrent chemoradiotherapy (CRT) with weekly cisplatin (30–40 mg/m²).
  • 1 patient received cetuximab with radiotherapy.
  • 7 patients received radiotherapy alone.
  • Radiotherapy doses ranged from 66.00 to 69.96 Gy for primary tumors and 50.96–59.96 Gy for prophylactic nodal regions, delivered via IMRT (30 patients) or 3D conformal radiotherapy (1 patient).

S+RT Group:

  • Surgical procedures included total laryngectomy (n=9), partial laryngectomy/hypopharyngectomy (n=10), and transoral wide resection (n=6).
  • 18 patients underwent bilateral neck dissection; 1 had unilateral dissection.
  • Postoperative radiotherapy doses ranged from 55–66 Gy to tumor beds and 45–60 Gy to prophylactic areas.
  • 15 patients received concurrent weekly cisplatin (30–40 mg/m²).

Statistical Analysis

Survival outcomes (OS, LRFS, DMFS) were analyzed using Kaplan-Meier estimates and Cox proportional hazards models. Acute toxicity was graded per RTOG criteria.

Results

Survival Outcomes

Overall Survival (OS):

  • The 1-, 2-, and 5-year OS rates were 80.6%, 53.4%, and 24.7% for the DRT group versus 85.7%, 67.1%, and 24.7% for the S+RT group (P=0.074) (Figure 1).
  • No significant difference was observed between the two groups (χ²=3.183).

Local Recurrence-Free Survival (LRFS):

  • The 1-, 2-, and 5-year LRFS rates were 90.4%, 61.7%, and 18.0% for DRT versus 96.4%, 55.7%, and 20.3% for S+RT (P=0.868).

Distant Metastasis-Free Survival (DMFS):

  • The 1-, 2-, and 5-year DMFS rates were 87.4%, 49.2%, and 9.9% for DRT versus 96.3%, 57.1%, and 15.9% for S+RT (P=0.067).

Subgroup Analysis

Primary Tumor Site:

  • Supraglottic Carcinoma: 5-year OS was 15.3% (DRT) vs. 51.4% (S+RT), but differences were not statistically significant (P=0.149) (Figure 2A).
  • Hypopharyngeal Carcinoma: 5-year OS was 51.5% (DRT) vs. 71.8% (S+RT), again without significant divergence (P=0.255) (Figure 2B).

Stage IV Disease:

  • S+RT demonstrated superior 5-year OS (42.9% vs. 22.5% for DRT; P=0.003) (Figure 3).

Treatment Response and Toxicity

  • DRT Group: 87.1% achieved complete response (CR) in primary tumors; 77.4% had CR in nodal disease.
  • Acute Toxicity: Comparable rates of mucositis, myelosuppression, and dysphagia were observed between groups (Table 3).

Multivariate Analysis

Cox regression identified advanced stage (HR=6.719, P=0.011) and treatment modality (HR=0.319, P=0.028) as significant prognostic factors for survival.

Discussion

Organ Preservation and Survival Equivalence

The study demonstrated comparable survival outcomes between DRT and S+RT, supporting DRT as a viable organ-preserving strategy. For early-stage disease (I/II), both modalities yielded excellent survival, with no deaths attributed to cancer recurrence. However, for stage IV tumors, S+RT showed significantly better OS, likely due to improved local control from surgical resection of bulky disease.

Functional Outcomes

Laryngeal preservation was achieved in 59.3% of DRT patients, a critical factor in maintaining QOL. Notably, 22% of S+RT patients retained partial laryngeal function, underscoring advances in conservative surgical techniques. Transoral laser microsurgery (TLM) and robotic surgery (TORS) may further enhance functional preservation while reducing morbidity.

Role of Systemic Therapy

Concurrent cisplatin-based chemotherapy improved locoregional control but was underutilized in both cohorts. Only 50% of DRT and 53% of S+RT patients completed ≥5 chemotherapy cycles, highlighting the need for optimized supportive care to enhance treatment adherence.

Limitations and Future Directions

The retrospective design and small sample size limit generalizability. Larger prospective studies are needed to validate these findings and refine patient selection criteria for organ preservation versus radical surgery.

Conclusion

In supraglottic and hypopharyngeal carcinoma, definitive radiotherapy achieves survival outcomes comparable to surgery combined with adjuvant radiotherapy, with the added benefit of laryngeal preservation. For advanced-stage disease, multimodal approaches integrating surgery and radiotherapy may optimize survival while balancing functional outcomes.

doi.org/10.1097/CM9.0000000000000515

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