Nationwide Validation of the 8th American Joint Committee on Cancer TNM Staging System and Five Proposed Modifications for Resected Pancreatic Cancer

Abstract

Background The prognostic value of four proposed modifications to the 8th American Joint Committee on Cancer (AJCC) TNM staging system has yet to be evaluated. This study aimed to validate five proposed modifications. Methods Patients who underwent pancreatic ductal adenocarcinoma resection (2014–2016), as registered in the prospective Dutch Pancreatic Cancer Audit, were included. Stratification and prognostication of TNM staging systems were assessed using Kaplan–Meier curves, Cox proportional hazard analyses, and C-indices. A new modification was composed based on overall survival (OS). Results Overall, 750 patients with a median OS of 18 months (interquartile range 10–32) were included. The 8th edition had an increased discriminative ability compared with the 7th edition {C-index 0.59 (95% confidence interval [CI] 0.56–0.61) vs. 0.56 (95% CI 0.54–0.58)}. Although the 8th edition showed a stepwise decrease in OS with increasing stage, no differences could be demonstrated between all substages; stage IIA vs. IB (hazard ratio [HR] 1.30, 95% CI 0.80–2.09; p = 0.29) and stage IIB vs. IIA (HR 1.17, 95% CI 0.75–1.83; p = 0.48). The four modifications showed comparable prognostic accuracy (C-index 0.59–0.60); however, OS did not differ between all modified TNM stages (ns). The new modification, migrating T3N1 patients to stage III, showed a C-index of 0.59, but did detect significant survival differences between all TNM stages (p < 0.05). Conclusions The 8th TNM staging system still lacks prognostic value for some categories of patients, which was not clearly improved by four previously proposed modifications. The modification suggested in this study allows for better prognostication in patients with all stages of disease.

The Concept of Stroma AReactive Invasion Front Areas (SARIFA) as a New Prognostic Biomarker for Lipid-driven Cancers Holds True in Pancreatic Ductal Adenocarcinoma

“…Compared with other tumour entities, in PDAC, there is a lack of biomarkers, and the 8th Union for International Cancer Control TNM staging system plays the most important yet debatable role in this context [20, 21], hence indicating the need for new biomarkers. Tumour budding, well established in colorectal cancer [22], did not enter routine and is, despite its broad acceptance as reliable prognostic biomarker, hampered by a relevant interobserver variability [23] because the standardisation and implementation of this marker has met some challenges, including demarcation of small-sized buds (up to five tumour cells) from surrounding cell-rich PDAC stroma, not only at the invasion front, but also at the tumour centre [24, 25].…”

Impact of preoperative CA19-9 and histology grade on prognosis of pancreatic ductal adenocarcinoma and its value in TNM stage

“…The AJCC TNM classi cation which re ects tumor burden was the most widely used staging system for malignancy, however, it was a macroscopic classi cation mainly based on anatomy and did not incorporate the factors re ecting microscopic tumor burden which could not be detected by imageology [14] , neither the factors re ecting malignant degree of tumor. As a result, there were always biases of accuracy when the TNM stage was used to predict prognosis [8,9] . In the present study, we supposed to incorporate preoperative serum CA19-9, which could compensate the de ciency of TNM stage in evaluating microscopical tumor burden, and histology grate, which could make up for the defect of TNM stage in re ecting malignant degree, into the TNM staging system to reduce the biases.…”

“…The TNM classi cation has undergone continuous improvement to re ect the current understanding of the extent of disease [4] . Several studies have clari ed the accuracy of the TNM staging of Pancreatic Cancer (8th ed., 2017) [5,6,7] , in contrast, other studies demonstrated no survival differences between stages of TNM classi cation and proposed modi ed TNM or newly staging system [8,9] .…”

ASO Author Reflections: The Need for Improvement of the 8th American Joint Committee on Cancer TNM Staging System for Resected Pancreatic Ductal Adenocarcinoma

“…In this study, the prognostic value of the 8th AJCC TNM classification and proposed modifications was evaluated in a cohort of 750 consecutive patients who underwent PDAC resection in the Netherlands between 2014 and 2016. 6 The 8th edition distributed patients more equally over all disease stages as compared with the 7th edition and displayed increased prognostic accuracy (C-index 0.59 versus 0.56, respectively). In our cohort, the proposed modifications did not further improve its prognostic value.…”