J Gastric Cancer.  2018 Jun;18(2):142-151. 10.5230/jgc.2018.18.e14.

Modification of the TNM Staging System for Stage II/III Gastric Cancer Based on a Prognostic Single Patient Classifier Algorithm

• Choi YY
• Jang E
• Seo WJ
• Son T
• Kim HI
• Kim H
• Hyung WJ
• Huh YM
• Noh SH
• Cheong JH

• KMID: 2414534
• DOI: http://doi.org/10.5230/jgc.2018.18.e14

Abstract

PURPOSE
The modification of the cancer classification system aimed to improve the classical anatomy-based tumor, node, metastasis (TNM) staging by considering tumor biology, which is associated with patient prognosis, because such information provides additional precision and flexibility.
MATERIALS AND METHODS
We previously developed an mRNA expression-based single patient classifier (SPC) algorithm that could predict the prognosis of patients with stage II/III gastric cancer. We also validated its utilization in clinical settings. The prognostic single patient classifier (pSPC) differentiates based on 3 prognostic groups (low-, intermediate-, and high-risk), and these groups were considered as independent prognostic factors along with TNM stages. We evaluated whether the modified TNM staging system based on the pSPC has a better prognostic performance than the TNM 8th edition staging system. The data of 652 patients who underwent gastrectomy with curative intent for gastric cancer between 2000 and 2004 were evaluated. Furthermore, 2 other cohorts (n=307 and 625) from a previous study were assessed. Thus, 1,584 patients were included in the analysis. To modify the TNM staging system, one-grade down-staging was applied to low-risk patients according to the pSPC in the TNM 8th edition staging system; for intermediate- and high-risk groups, the modified TNM and TNM 8th edition staging systems were identical.
RESULTS
Among the 1,584 patients, 187 (11.8%), 664 (41.9%), and 733 (46.3%) were classified into the low-, intermediate-, and high-risk groups, respectively, according to the pSPC. pSPC prognoses and survival curves of the overall population were well stratified, and the TNM stage-adjusted hazard ratios of the intermediate- and high-risk groups were 1.96 (95% confidence interval [CI], 1.41-2.72; P < 0.001) and 2.54 (95% CI, 1.84-3.50; P < 0.001), respectively. Using Harrell's C-index, the prognostic performance of the modified TNM system was evaluated, and the results showed that its prognostic performance was better than that of the TNM 8th edition staging system in terms of overall survival (0.635 vs. 0.620, P < 0.001).
CONCLUSIONS
The pSPC-modified TNM staging is an alternative staging system for stage II/III gastric cancer.

Keyword

Classification; gastric cancer; staging; prognosis; biomarker

MeSH Terms

Biology
Classification
Cohort Studies
Gastrectomy
Humans
Neoplasm Metastasis
Neoplasm Staging*
Pliability
Prognosis
RNA, Messenger
Stomach Neoplasms*
RNA, Messenger

Figure

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  Fig. 1 Classification of the Kaplan-Meier curves and Cox survival estimates for the OS of patients using the pSPC in Cohort_C and in the overall population. (A) Kaplan-Meier curves of the patients in Cohort_C, (B) Kaplan-Meier curves of the patients in the overall population, (C) Cox survival estimates that were adjusted by TNM stages in Cohort_C, and (D) Cox survival estimates that were adjusted by TNM stages in the overall population.OS = overall survival; pSPC = prognostic single patient classifier; TNM = tumor, node, metastasis; HR = hazard ratio; CI = confidence interval.

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  Fig. 2 Classification of the Kaplan-Meier curves for the OS of patients using the pSPC in each stage; (A) stage IIA, (B) stage IIB, (C) stage IIIA, and (D) stage IIIB, according to AJCC 8th edition staging system.OS = overall survival; pSPC = prognostic single patient classifier; AJCC = American Joint Committee on Cancer.

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  Fig. 3 Kaplan-Meier curves for the OS and DFS of the AJCC 8th edition and revised TNM staging systems; (A) OS of the AJCC 8th edition staging system, (B) OS of the modified TNM, (C) DFS of the AJCC 8th edition staging system, and (D) DFS of the modified TNM staging system.OS = overall survival; DFS = disease-free survival; AJCC = American Joint Committee on Cancer; TNM = tumor, node, metastasis.

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