Clinical outcomes of residual or recurrent nasopharyngeal carcinoma treated with endoscopic nasopharyngectomy plus chemoradiotherapy or with chemoradiotherapy alone: a retrospective study

Abstract

Background: Local residual and recurrent nasopharyngeal carcinoma (NPC) generally shows treatment failure after standard radiotherapy with or without concurrent chemotherapy. Whether endoscopic nasopharyngectomy might provide an additional therapeutic advantage remains controversial. Therefore, we retrospectively compared the clinical prognoses of patients with residual or recurrent NPC treated with endoscopic nasopharyngectomy combined with chemoradiotherapy (CRT) with those of patients treated with CRT alone.

Methods and materials: A total of sixty-two patients with local residual or recurrent NPC were studied retrospectively: 36 patients received endoscopic nasopharyngectomy combined with CRT, whereas 26 patients who refused the surgery or had surgical contraindications received CRT alone. Serum Epstein-Barr virus (EBV) DNA levels were measured pre- and post-treatment. The differences in prognosis between the two treatment regimens and the pre- and post-treatment changes in EBV-DNA levels were analyzed.

Results: The median follow-up time was 31 months, with a 3-year overall survival (OS) of 51.40% and a 3-year disease-free survival (DFS) of 46.86%. The surgery + CRT group had a better OS than the CRT alone group did (χ² = 4.054, P = 0.044). The pretreatment EBV-DNA levels showed a positive correlation with the clinical staging of recurrent NPC (χ² = 11.674, P = 0.009). Patients with negative pretreatment serum EBV-DNA levels showed a superior OS to those of patients who tested positive for EBV-DNA (>0 copy/mL) (χ² = 9.833, P = 0.002). The post-treatment EBV-DNA levels, compared with the pretreatment levels, decreased significantly in the surgery + CRT group (Z = - 3.484, P = 0.000). In contrast, the EBV-DNA levels after CRT alone did not decrease significantly (Z = - 1.956, P = 0.051). Multivariate analysis indicated that local staging, pretreatment EBV-DNA load, and the treatment method were independent risk factors for OS. Subgroup analysis indicated that the patients who tested negative for EBV-DNA before the treatment and those who received surgery + CRT showed a better OS than those who received CRT alone.

Conclusions: The pretreatment serum EBV-DNA level was associated with disease prognosis. The combination therapy preceded by surgery can effectively decrease the copy number of EBV-DNA. Patients with local intermediate- and late-stage NPC, especially those negative for EBV-DNA, may consider opting for surgery followed by post-operative adjuvant radiotherapy or chemotherapy.

Keywords: Nasopharyngeal carcinoma; Prognosis; Recurrent tumor; Residual tumor; Serum epstein-barr virus DNA load.

Figure 1. Pre- and post-operative MRI and high-definition endoscopic images.

(A) Pre-operative MRI shows that the tumor is located in the right pharyngeal recess (rT1). (B) The 6-months post-operative MRI did not show tumor recurrence. (C and D) The 6-months post-operative endoscopic examination images show no visible tumor recurrence. Labels in the pre-operative endoscopic images: a, nasopharyngeal posterior wall; b, right torus tubarius; c, nasopharyngeal carcinoma. Post-operative: a, soft palate; b, nasopharyngeal posterior wall; c, nasopharyngeal right wall. (E) Pre-operative MRI shows the tumor invading the left pharyngeal space (rT2). (F) Post-operative MRI after six months did not show tumor recurrence; (G & H) The 6-months post-operative endoscopic examination images show no visible tumor recurrence. Labels in the Pre-operative endoscopic images: d, nasal septum; e, soft palate; f, right torus tubarius; g, nasopharyngeal carcinoma; Post-operative: d, nasal septum; e, soft palate; f, nasopharyngeal right wall; g, clivus. (I) Pre-operative MRI shows the tumor invading the base of the skull (rT3); (J) post-operative MRI after six months did not show tumor recurrence; (K and L) The 6-months post-operative endoscopic examination images show no visible tumor recurrence. Labels in the pre-operative endoscopic images: h, nasal septum; i, nasopharyngeal posterior wall; j, right torus tubarius; k, nasopharyngeal carcinoma; Post-operative: h, nasal septum; i, nasopharyngeal posterior wall; j, nasopharyngeal right wall; k, clivus.

Figure 2. Correlation of EBV-DNA level with staging and treatment methods.

(A) Comparison of pre-treatment EBV-DNA levels among different T stages; (B) Changes in EBV-DNA levels between different treatment methods.

Figure 3. Kaplan–Meier analysis of overall survival among patients with residual or recurrent NPC.

(A) T stages; (B) Treatment methods; (C) Pre-treatment EBV-DNA; (D) Post-treatment EBV-DNA.

Figure 4. Kaplan–Meier analysis of disease-free survival among patients with residual or recurrent nasopharyngeal carcinoma.

(A) T stages; (B) Treatment methods; (C) Pre-treatment EBV-DNA; (D) Post-treatment EBV-DNA.

Figure 5. Kaplan–Meier analysis of clinical prognosis among subgroups of patients with residual or recurrent nasopharyngeal carcinoma.

(A) Overall survival (OS) comparison of different treatment methods in local early-stage patients; (B) Disease-free survival (DFS) comparison of different treatment methods in local early-stage patients; (C) OS comparison of different treatment methods in local late-stage patients; (D) DFS comparison of different treatment methods in local late-stage patients.

Figure 6. Kaplan–Meier analysis of clinical prognosis among the subgroups of patients with residual or recurrent nasopharyngeal carcinoma.

(A) Overall survival (OS) of different treatment methods among EBV-DNA(−) patients; (B) Disease-free survival (DFS) comparison of different treatment methods among EBV-DNA(−) patients; (C) OS comparison of different treatment methods among EBV-DNA(+) patients; (D) DFS comparison of different treatment methods among EBV-DNA (+) patients.