Multi-institutional Validation Study of the American Joint Commission on Cancer (8th Edition) Changes for T and N Staging in Patients With Pancreatic Adenocarcinoma

Abstract

Objective: The aim of this study was to evaluate and validate the proposed 8th edition American Joint Committee on Cancer (AJCC) system for T and N staging of pancreatic adenocarcinoma.

Summary of background data: Investigators have questioned the clinical relevance and reproducibility of previous AJCC staging for pancreatic adenocarcinoma.

Methods: Prospective databases at Memorial Sloan Kettering (MSK), Massachusetts General Hospital (MGH), and Johns Hopkins Hospital (JHH) were queried for patients who had undergone resection for pancreatic adenocarcinoma. Patients who underwent a margin-negative (R0) resection, and who had previously undergone pathologic review, were included. Patients were staged according to 7th edition AJCC criteria, as well as the proposed 8th edition system that includes different definitions of tumor size (T) and nodal status (N). The dataset was randomly split into training and test sets.

Results: Two thousand three hundred eighteen patients were identified who met inclusion criteria. Recursive partitioning on the training set (n = 1551) identified statistically appropriate cutoffs for tumor size (<2.2 cm, ≥4.8 cm,) and nodal status (no positive nodes, 1 to 3 positive nodes, ≥4 positive nodes) that supported the proposed 8th edition changes. Median survival in patients staged as T3, N0 by the 7th edition definitions was different between institutions (median Center 1, 24 mo; Center 2, 37 mo; Center 3, 29 mo; P = 0.054). This difference was not observed when patients were staged as T3, N0 by 8th edition criteria. Stage, and stage-specific outcome (7th edition), on the test set revealed a predominance of patients (68%) within the IIB subgroup, and a concordance probability estimate (CPE) of 0.57 for stage-specific survival. When assessed with 8th edition criteria, no stage subgroup had a majority of patients, and the CPE was 0.58.

Conclusions: The proposed 8th edition changes for T and N classification were statistically valid and may allow a more reproducible system of T staging. This system also stratifies patients more evenly across stages without sacrificing prognostic accuracy.

Figure 1

Overall survival by T-stage of 767 patients who underwent resection for node-negative pancreatic cancer. T-stage defined by AJCC 7^th edition criteria.

Figure 2

Overall survival of 767 patients who underwent resection for node-negative pancreatic cancer. 2A: Overall survival stratified by institution. 2B: Overall survival of T3, N0 patients (AJCC 7^th edition) stratified by institution. 2C: Overall survival of T3, N0 patients (AJCC 8^th edition) stratified by institution.

Figure 3

Overall survival by T-stage of 525 patients who underwent resection for node-negative pancreatic cancer stratified by proposed AJCC 8^th edition criteria (training set only).

Figure 4

Overall survival by number of positive nodes for all patients who underwent a R0 resection (training set, n=1551) stratified by proposed AJCC 8^th edition criteria.