Equipping the American Joint Committee on Cancer Staging for Resectable Pancreatic Ductal Adenocarcinoma with Tumor Grade: A Novel Staging System

Abstract

Background. The 8th American Joint Committee on Cancer (AJCC) staging system for pancreatic ductal adenocarcinoma (PDAC) outperforms its previous version in reproducibility but not in survival discrimination. Tumor grade, an indicator of the aggressive biology of PDAC, has been suggested as a reliable prognostic factor. This study aimed to construct a novel staging system with greater prognostication for resectable PDAC by incorporating tumor grade into the 8th AJCC system. Methods. A total of 9966 patients with resectable PDAC from the Surveillance Epidemiology and End Results (SEER) database were randomly separated into training and interval validation sets. Another 324 patients from our center were included as an external validation set. We proposed a novel staging system by sorting the substages yielded by a combination of T, N, and tumor grade based on their overall survival (OS) and grouping them into several stages. Prognostic homogeneity and discrimination were determined using the likelihood ratio χ2 and the linear trend χ2 test, respectively. Prognostic accuracies were evaluated by the area under the receiver operating characteristics curve (AUC). Results. Using the 8th AJCC system, the prognosis of patients within the same stage was quite heterogeneous among different substages. The multivariate Cox model identified the tumor grade (hazard ratio 1.333, 95% confidence interval 1.250–1.423, p<0.001) was an independent prognostic factor of the OS. In the training set, the AUC, homogeneity, and discriminatory ability were superior for the novel staging system than for the 8th AJCC system (0.642 vs. 0.615, 403.4 vs. 248.6, and 335.1 vs. 218.0, respectively). Similar results were observed in the internal and external validation sets. Conclusions. The novel staging system incorporating tumor grade into the 8th AJCC system was associated with better prognostic accuracy, homogeneity, and discriminatory ability among resectable PDAC patients. Moreover, the novel staging system also allowed possibly adjuvant chemotherapy decisions.

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

“… 19 Nevertheless, most studies proposing modifications of the 8th TNM classification maintained the 8th AJCC definitions for T and N stage. 25 , 26 , 40 , 41 In our cohort, the 8th T and N stages were both found to be associated with OS, thereby significantly adding to the prognostic ability of the TNM staging system.…”

High expression of both desmoplastic stroma and epithelial to mesenchymal transition markers associate with shorter survival in pancreatic ductal adenocarcinoma

“…The AJCC has also incorporated the degree of tumor differentiation (G) as a further criterion. 7 Together with the TNM, the degree of tumor differentiation determines patient prognosis. 6 The G criterion categorizes the tumor from well-differentiated (low grade) to undifferentiated (high grade); the more undifferentiated the tumor is, the more aggressive its biological behavior is.…”

“…If more than 95% of a tumor is composed of glands, it is classified as well-differentiated; if 50-95% of the tumor is composed of glands, it is moderately differentiated; and if less than 50% of it is composed of glands, it is poorly differentiated. 6 Several studies have shown that the degree of tumor differentiation of pancreatic cancer is a key indicator of survival after tumor resection, 7-10 although both AJCC criteria fail to explain the variability in the survival of patients with PDAC. Thus, 80% of patients with PDAC are diagnosed at advanced clinical stages and with a worse prognosis 2 , 11 and the 5-year overall survival rate is 9%.…”