A novel prognostic system for locally advanced gastrointestinal stromal tumors after neoadjuvant imatinib therapy based on the metro-ticket paradigm: a retrospective dual-center study.

Abstract

Background: Accurately assessing the mitotic index after neoadjuvant therapy remains challenging, which limits the prognostic utility of the NIH criteria. The tumor regression grade (TRG), which evaluates therapeutic efficacy on the basis of tumor necrosis, can increase the prognostic capacity when integrated with ypT staging in patients receiving preoperative imatinib therapy. The aim of this study was to develop a staging system incorporating TRG and ypT staging to assess patient outcomes and guide surgical strategies and postoperative adjuvant therapy in patients with locally advanced gastrointestinal stromal tumors (LA-GIST) treated with preoperative imatinib.

Methods: A retrospective analysis was conducted on 200 patients with LA-GIST who received preoperative imatinib therapy at two high-volume centers. The ypT-TRG staging system was constructed by computing the Euclidean distance of each TRG (x-axis) and ypT stage (y-axis) coordinate from the origin in a Cartesian plane.

Results: Compared with the NIH criteria, the ypT-TRG staging system provided a more balanced distribution of patients, with 61% (n = 122) experiencing risk reclassification. The ypT-TRG system demonstrated superior discriminatory ability (concordance index), model fit (Akaike information criterion, Bayesian information criterion), risk reclassification improvement (net reclassification improvement, integrated discrimination improvement), dynamic predictive performance (time-dependent receiver operating characteristic curve), and clinical utility (decision curve analysis). Furthermore, multivariate Cox regression analysis confirmed that ypT-TRG stage could replace the NIH criteria as an independent prognostic factor. Notably, patients classified as ypT-TRG stages I-II had a significantly higher rate of minimally invasive surgery (83.9% vs. 45.1%, P < 0.001). In addition, patients with stages III-IV disease achieved significant survival benefits from prolonged postoperative imatinib therapy.

Conclusion: Compared with the NIH criteria, the ypT-TRG staging system provides superior prognostic stratification for patients with LA-GIST. This system offers valuable insights for selecting candidates for minimally invasive surgery and facilitates the optimization of postoperative imatinib treatment strategies.