Development and validation of a staging system for gastric adenocarcinoma after neoadjuvant chemotherapy and gastrectomy with D2 lymphadenectomy

Abstract

Background: Neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy is commonly used for patients with locally advanced gastric adenocarcinoma. The eighth AJCC ypTNM staging system was validated based on patients undergoing more limited lymphadenectomy (less than D2). The aim of this study was to develop a system for accurate staging of patients with locally advanced gastric adenocarcinoma who receive neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy.

Methods: A modified system of ypTNM was developed, based on overall survival (OS) of patients receiving neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy at Memorial Sloan Kettering Cancer Center, and validated using data from an international cohort of patients who had similar treatment.

Results: Of 325 patients in the derivation cohort, 33 (10·2 per cent) had ypT0 N0/+ tumours, which are not classifiable under the AJCC system. The 5-year OS rate for modified ypTNM stages I, II, IIIA and IIIB was 89, 71, 42·3 and 10 per cent respectively, compared with 82, 65·2 and 24·1 for AJCC stages I, II and III respectively. The concordance index (0·730 versus 0·709), estimated area under the curve (0·765 versus 0·740) and time-dependent receiver operating characteristic (ROC) curve throughout the observation period were all superior for modified ypTNM staging. For the validation cohort of 186 patients, the modified system was again better at separating patients into prognostic groups for OS.

Conclusion: The modified ypTNM staging system improves the accuracy of OS prediction for patients treated with neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy.

Figure 1.

Overall survival of the training set based on two staging systems. (A) Kaplan-Meier overall survival for the training set according to 8^th edition AJCC ypTNM stage, with the addition of ypT0N0 and ypT0N+. (B) AJCC ypTNM staging system and modified ypTNM staging system. (C) Kaplan-Meier overall survival for the training set according to modified ypTNM stage.

Figure 2.

Survival discrimination and prognostic accuracy of the 8^th edition AJCC and modified ypTNM staging systems for the training set. ROC curves (A) and time-dependent ROC curves (B) for the AJCC ypTNM and m-ypTNM staging systems. Solid lines represent time dependent ROC curves and dotted lines represent 95% confidence intervals.

Figure 3.

Kaplan-Meier overall survival in the validation set according to AJCC TNM stage (A) and modified ypTNM stage (B). (C) Time-dependent ROC curves for the 8th edition AJCC and modified ypTNM staging systems.