Re-appraisal of the universal definition of tumor rupture among patients with high-risk gastrointestinal stromal tumors

Aim: Tumor rupture has been indicated as a risk factor for recurrence of gastrointestinal stromal tumors (GISTs). The universal definition of tumor rupture was proposed. This study evaluated whether the universal definition was more accurate in identification of GISTs with high recurrent risk than subjective judgment.Methods: The study included 507 patients with high-risk GISTs who underwent complete resection between December 2012 and December 2015. We conducted a questionnaire survey in participating institutes to re-diagnose tumor rupture based on the universal definition according to their surgical and pathological findings. We compared the clinical outcomes of tumor rupture based on the definition to those based on the surgeon's judgment and clarified the clinical importance of the rupture.Results: Sixty-four patients were initially registered to have tumor rupture by surgeon's judgment, and it became 90 patients who had tumor rupture after reevaluation. Although there were significant differences in recurrence-free survival (RFS) between no rupture and rupture for both initial registration and reevaluation (p = 0.002, <0.001, respectively), a significant difference in overall survival was only observed after reevaluation (p = 0.011). Tumor rupture was significantly associated with large tumor size, mixed cell type in histology, R1 resection, frequent adjuvant therapy and recurrence, but not with location, mitosis, and genotype. Adjuvant therapy more than 3 years improved RFS of patients with tumor rupture.Conclusion: This study suggested that tumor rupture based on the universal definition more accurately identified GISTs with poor prognostic outcomes than the subjective judgment.