Prognostic Factors for Overall Survival in Nasopharyngeal Cancer and Implication for TNM Staging by UICC: A Systematic Review of the Literature

Abstract

This study aims to identify prognostic factors in nasopharyngeal carcinoma (NPC) to improve the current 8th edition TNM classification. A systematic review of the literature reported between 2013 and 2019 in PubMed, Embase, and Scopus was conducted. Studies were included if (1) original clinical studies, (2) ≥50 NPC patients, and (3) analyses on the association between prognostic factors and overall survival. The data elements of eligible studies were abstracted and analyzed. A level of evidence was synthesized for each suggested change to the TNM staging and prognostic factors. Of 5,595 studies screened, 108 studies (44 studies on anatomical criteria and 64 on non-anatomical factors) were selected. Proposed changes/factors with strong evidence included the upstaging paranasal sinus to T4, defining parotid lymph node as N3, upstaging N-category based on presence of lymph node necrosis, as well as the incorporation of non-TNM factors including EBV-DNA level, primary gross tumor volume (GTV), nodal GTV, neutrophil-lymphocyte ratio, lactate dehydrogenase, C-reactive protein/albumin ratio, platelet count, SUVmax of the primary tumor, and total lesion glycolysis. This systematic review provides a useful summary of suggestions and prognostic factors that potentially improve the current staging system. Further validation studies are warranted to confirm their significance.

Establishment of a prognostic nomogram for patients with locoregionally advanced nasopharyngeal carcinoma incorporating clinical characteristics and dynamic changes in hematological and inflammatory markers

“…In recent years, there has been growing interest in incorporating non-anatomical prognostic factors into the staging system. These variables may be relevant for individualized risk stratification and guiding the treatment intensity ( 4 ).…”

“…EBV-DNA levels provide information on tumor biological behavior beyond the anatomical staging. It has been hypothesized that the prognostic performance of the staging system can potentially be improved by including EBV-DNA levels ( 4 ). However, its wide application has been limited due to heterogeneity in laboratory techniques ( 57 ).…”

“…Despite substantial improvement in radiotherapy techniques and concurrent chemotherapy for NPC, many patients suffer from localregional recurrence and distant metastasis (3). A metaanalysis by Chiang et al identified a set of significant prognostic factors including primary gross tumor volume (GTV), Epstein-Barr virus (EBV)-DNA level, lactate dehydrogenase (LDH), C-reactive protein/albumin ratio, platelet count, and the maximum standard uptake value (SUVmax) of the primary tumor (4). In particular, there is a strong association between NPC and EBV infection.…”

Quantitative Spatial Characterization of Lymph Node Tumor for N Stage Improvement of Nasopharyngeal Carcinoma Patients

“…Over the past decades, various new LN anatomical descriptors have been proposed to improve the current N staging system [12]. For instance, parotid lymph node (PLN) involvement was found to be associated with a poor prognosis in distant metastasis, and an upgrade to the N3 classification was recommended [13,14].…”

Exploration of a Novel Prognostic Risk Signature and Its Effect on the Immune Response in Nasopharyngeal Carcinoma

“…The American Joint Committee Cancer (AJCC) tumor-nodemetastasis (TNM) staging system is considered to be the standard for prognostic predictions for NPC. However, the value of this system in evaluating the prognosis of NPC patients is limited, because the clinical outcomes are diverse among patients with the same TNM stage who receive similar treatment (8). Thus, molecular markers that can classify patients into groups based on good prognosis and poor prognosis have great clinical value.…”