In a Chinese phase III trial reported in The Lancet Oncology, Liu et al found that endoscopic nasopharyngectomy was associated with improved overall survival vs intensity-modulated radiotherapy (IMRT) in patients with resectable locally recurrent nasopharyngeal carcinoma who had received prior radiotherapy.
Study Details
In the open-label trial, 200 patients from three sites in southern China were randomly assigned between September 2011 and January 2017 to receive endoscopic nasopharyngectomy (n = 100) or IMRT (n = 100). Patients had to have undifferentiated or differentiated, nonkeratinizing, locally recurrent nasopharyngeal carcinoma with tumors confined to the nasopharyngeal cavity, postnaris or nasal septum, superficial parapharyngeal space, or base wall of the sphenoid sinus.
IMRT was delivered at 60 to 70 Gy in 27 to 35 fractions for the planning target volumes derived from the gross tumor volume of the primary site and lymph nodes and at 50 to 60 Gy for volumes derived from clinical target volumes, with five daily fractions given per week. The primary endpoint was overall survival compared between the groups at 3 years on intention-to-treat analysis.
Overall Survival
Median follow-up was 56.0 months (interquartile range [IQR] = 42.0–69.0 months). Overall, 29 patients (29%) in the endoscopic nasopharyngectomy group and 45 (45%) in the IMRT group had died.
The 3-year overall survival was 85.8% (95% confidence interval [CI] = 78.9%–92.7%) in the endoscopic nasopharyngectomy group vs 68.0% (58.6%–77.4%) in the IMRT group (hazard ratio [HR] = 0.47, 95% CI = 0.29–0.76, P = .0015). Overall survival at 5 years was 73.8% vs 57.2%.
At 3 and 5 years:
- Disease-free survival was 76.5% vs 56.5% and 59.0% vs 42.4% (HR = 0.54, 95% CI = 0.36–0.81, P = .0026)
- Locoregional recurrence–free survival was 89.8% vs 78.2% and 77.0% vs 66.6% (HR = 0.51, 95% CI = 0.28–0.93)
- Distant metastasis–free survival was 92.5% vs 87.8% and 80.7% vs 83.4% (HR = 1.01, 95% CI = 0.47–2.19).
Toxicity
Grade ≥ 3 radiotherapy-related late adverse events occurred in 13% of patients in the endoscopic nasopharyngectomy group vs 37% of the IMRT group. Death due to late radiotherapy toxic effects occurred in 5% vs 20% of patients; as noted by the investigators, “Attribution to previous radiotherapy or trial radiotherapy is unclear due to the long-term nature of radiation-related toxicity.”
Acute grade 3 toxicities (no grade 4 or 5 toxicities observed) occurred in 34% of the IMRT group. Grade 3 or 4 adverse events related to surgery (no grade 5 events observed) occurred in 6% of the endoscopic nasopharyngectomy group.
The investigators concluded, “Endoscopic surgery significantly improved overall survival compared with IMRT in patients with resectable locally recurrent nasopharyngeal carcinoma. These results suggest that endoscopic nasopharyngectomy could be considered as the standard treatment option for this patient population, although long-term follow-up is needed to further determine the efficacy and toxicity of this strategy.”
Wei-Ping Wen, MD, of the First Affiliated Hospital and Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the Sun Yat-sen University Clinical Research 5010 Program. For full disclosures of the study authors, visit thelancet.com.
