New surgical staging system for patients with recurrent nasopharyngeal carcinoma based on the AJCC/UICC rTNM classification system
Introduction
The American Joint Committee on Cancer (AJCC/UICC) tumour, node and metastasis (TNM) staging [1] is the most commonly used cancer staging system for newly diagnosed nasopharyngeal carcinoma (NPC). According to the 2011 National Comprehensive Cancer Network (NCCN) guidelines for head and neck cancer [2], concurrent chemoradiotherapy with or without induction chemotherapy is the standard treatment for T1 N1-3 M0 or T2-4 N any M0 patients. In addition, palliative platinum-based combination chemotherapy is recommended as the primary treatment for patients with distant metastases (any T, any N and M1). The five-year overall survival (OS) rates for non-metastatic NPC patients treated with intensity-modulated radiation therapy (IMRT) were 100%, 94.3%, 83.6% and 70.4% for stages I, II, III and IV, respectively [3].
However, 8.4–10.9% of patients developed recurrent disease at the primary or/and regional site after definitive radiotherapy [4], [5]. The current recurrent AJCC/UICC TNM stage system (rTNM) uses the ‘r’ prefix to denote the TNM stage for relapse patients. Therefore, rTNM staging ignores the striking differences between recurrent and primary patient populations, and the system may exhibit reduced critical accuracy when applied to recurrent diseases. For example, according to the sixth AJCC TNM staging manual [1], the survival of stage III recurrent nasopharyngeal carcinoma (rNPC) patients is similar to those re-staged as stage IV even when administered the same IMRT treatment method, thus indicating minimal difference between rT3 and rT4 [6], [7]. Furthermore, rN classification exhibited no prognostic significance regarding OS [6]. As a well-established technique, radiotherapy plays an important role as a salvage treatment for rNPC patients and is applied in all rT1–rT4 classifications [6], [7]. However, reduced radiation tolerance in the proximity of critical structures limits the application of salvage re-irradiation to those types of recurrences [8]. Endoscopic nasopharyngectomy (ENPG) is the most reasonable choice for rNPC. However, only some patients with limited lesions are suitable for salvage surgery [9]. Chemotherapy is also applicable for the management of rNPC but only serves as a palliative treatment [10]. In general, many modalities, including salvage surgery, re-irradiation and chemotherapy, are effective treatments for rNPC patients; however, none of these treatments were indicated according to the rTNM classification system. Thus, clinicians find it difficult to choose the most suitable treatment for rNPC patients in each stage. This fact prompted us to develop a specialised staging system for rNPC to correctly predict the survival of rNPC patients, aid the clinicians in planning treatments and facilitate clinical data sharing among different countries and hospitals.
Section snippets
Patient selection
Between 1st January 2000 and 31st December 2009, a total of 1102 consecutive patients with histologically or radiologically confirmed loco-regional recurrent diseases (first failures) who received radical radiotherapy initially before recurrence at the Sun Yat-sen University Cancer Center (SYSUCC) were enroled in this study. All of the patients with rNPC were initially staged according to the 2002 AJCC/UICC classification system [1]. Our exclusion criteria included (1) patients with missing
Clinicopathological characteristics
The clinicopathological characteristics of all 894 patients are presented in Appendix Table 1. On the final follow-up date (1st January 2013), the median follow-up was 50.35 months (range, 4.10–148.97 months) and a total of 494 patients died. The 5-year OS was 40.8%.
Recurrent T, N and M stages were converted into relative ‘surgical’ T, N and M stages
Totally, 385 patients underwent contrast-enhanced CT and the remaining 509 patients underwent MR imaging. Based on these imaging data, rNPC patients with rT2b, rT3, rN1, rN2 and rN3 were stratified into resectable or unresectable.
Discussion
An excellent staging system should both have a good prognostic value for survival outcome and be a good indicator of treatment choice. However, accumulating data have demonstrated that the popular rTNM staging system for rNPC does not meet these standards. Various specially designed recurrent staging systems were reported to demonstrate enhanced prognostic value for patients with recurrent head and neck cancers, such as recurrent laryngeal, oral cavity and oropharyngeal carcinoma [12], [13].
Conflict of interest statement
None declared.
Acknowledgements
This work was supported in part by the Program for New Century Excellent Talents in University of China (NCET-12-0562), Sun Yat-sen University – China Clinical Research 5010 Program (201310), Guangdong Provincial Natural Science Foundation of China (S2013020012726) and National High Technology Research and Development Program of China (863 Program, No. 2012AA02A501).
References (23)
- et al.
Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities
Radiother Oncol
(2014) - et al.
How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients?
Int J Radiat Oncol Biol Phys
(2011) - et al.
Long-term treatment outcome of recurrent nasopharyngeal carcinoma treated with salvage intensity modulated radiotherapy
Eur J Cancer
(2012) - et al.
Long-term outcomes and prognostic factors of re-irradiation for locally recurrent nasopharyngeal carcinoma using intensity-modulated radiotherapy
Clin Oncol (R Coll Radiol)
(2012) - et al.
Single-arm, multi-centre phase II study of lobaplatin combined with docetaxel for recurrent and metastatic nasopharyngeal carcinoma patients
Oral Oncol
(2014) - et al.
Endoscopic microwave coagulation therapy for early recurrent T1 nasopharyngeal carcinoma
Eur J Cancer
(2009) - Greene FL, Page DL. AJCC cancer staging handbook. 6th ed. New York, NY: Springer-Verlag; 2002. p....
- National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology for Head and Neck Cancer, Version...
- et al.
Survival outcome of patients with nasopharyngeal carcinoma with first local failure: a study by the Hong Kong Nasopharyngeal Carcinoma Study Group
Head Neck
(2005) - et al.
Long-term survival and late complications in intensity-modulated radiotherapy of locally recurrent T1–T2 nasopharyngeal carcinoma
Head Neck
(2014)
Endoscopic nasopharyngectomy for locally recurrent nasopharyngeal carcinoma
Laryngoscope
Cited by (41)
Endoscopic nasopharyngectomy in nasopharyngeal carcinoma
2021, Operative Techniques in Otolaryngology - Head and Neck SurgeryCitation Excerpt :The current recurrent AJCC/UICC TNM staging system (rTNM) uses the ‘r’ prefix to denote the TNM stage for relapse patients, which ignores the differences between recurrent and primary patient populations and exhibits reduced critical accuracy when applied to recurrent diseases. Chen et al established a new surgical staging system for patients with recurrent NPC based on the UICC/AJCC rTNM staging system and “resectable area.”11 In detail, UICC/AJCC recurrent T1-4 and recurrent N0-3 stages were divided into resectable and unresectable subgroups according to the “resectable area,” and there were 8 subgroups in rT stage and 7 subgroups in rN stage.
Establishment of a prognostic nomogram to identify optimal candidates for local treatment among patients with local recurrent nasopharyngeal carcinoma
2020, Oral OncologyCitation Excerpt :However, the usefulness of rTNM staging is limited, as the clinical outcomes differ among patients with the same stage [10]. According to the National Comprehensive Cancer Network guideline, the recurrent NPC patients are recommended to receive re-irradiation, endoscopic nasopharyngectomy, or palliative chemotherapy (PCT) as the main salvage therapy [10–13]. However, even these patients received salvage treatment mentioned above, the outcome still presented a huge discrepancy, which indicated that it was necessary to identify patients with different risk levels to provide patient counseling and individualized management [10,11,14].
- 1
Contributed equally to this study.