Proposed changes to the pathologic staging for colon cancer (CC): AJCC Colon Cancer Expert Panel (AJCCCCEP).

3520 Background: Recent analyses highlight nonhierarchical outcomes using the 8 th Edition AJCC staging system for CC. For instance, the 5-year survival rate for stages I and IIIa patients (pts) closely align. Additionally, tumor deposits (TDs) have been established as significant prognostic indicators. The AJCCCCEP commissioned this study to develop an updated pathological staging system for CC focused specifically on pts without distant metastasis (M0), while retaining the existing stage IV classification. Methods: Individual patient data (IPD) from pts diagnosed with cc (2010- 2017) in the NCDB were divided into training (70%) and internal validation (30%) datasets. External validation used IPD from clinical trials. The primary endpoint was overall survival (OS). Risk classification development for M0 pts incorporated ungrouped data on pathologic T categories, the number of involved regional lymph nodes (LN+), and TD counts. Recursive partitioning and regression tree analyses were applied to construct hierarchical staging levels. Pre-specified criteria required survival probabilities to be consecutive and show clear separations using Kaplan-Meier (KM) estimates with pairwise log-rank test P of < 0.005 for the training and < 0.05 for validation analyses. Results: Data from 281,997 pts (median age 67 years, 50% male, 81% white, 55% T3, 19% T4, 44% N+, 26% M+, and 11% with ≥1 TD) were analyzed, with a median follow-up of 7.3 years. The updated staging system (Table) met pre-specified criteria, with all observed pairwise P < 0.0001 in the development and internal validation sets. KM OS curves displayed a hierarchical separation across all sub-levels after the 1 st year of diagnosis. Consistent results were seen in pts treated with adjuvant chemotherapy in 4 trials (all pair-wise P < 0.0001). Conclusions: The proposed pathological staging system for M0 pts fulfills pre-specified criteria for hierarchical risk stratification, validated both internally and externally, and provides an evidence-based update. Pending review process, the AJCCCCEP will recommend that these changes be made to the Version 9 staging protocol for colon cancer to improve prognostication for CC pts. Stage T, # of LN+, # of TD M % of pts 1y OS (CI), % 3y OS (CI), % 5y OS (CI), % I T1, 0, 0 0 5 96 (95-97) 91 (90-92) 84 (83-86) IIa T2, 0, 0 0 10 95 (94-95) 88 (88-89) 80 (79-81) IIb T1, 0, 1+T1, 1+, 0T2, 0, 1+T2, 1-4, 0T3, 0, 0 0 27 93 (92-93) 84 (84-85) 75 (75-76) IIIa T1, 1+, 1+T2, 1-4, 1+T2, 5+, 0T3, 0, 1+T3, 1-4, 0 0 14 92 (91-92) 80 (80-81) 71 (70-72) IIIb T2, 5+, 1+T3, 1-4, 1+T3, 5+, 0T4a, 0-4, 0T4b, 0-2, 0 0 13 86 (86-87) 69 (68-70) 58 (57-59) IIIc T3, 5+, 1+T4a, 0-4, 1+T4a, 5+, anyT4b, 0-2, 1+T4b, 3+, any 0 5 78 (77-80) 53 (51-54) 40 (38-41) IVa Any 1a 19 59 (58-60) 28 (28-29) 17 (16-18) IVb Any 1b 7 43 (42-44) 14 (13-14) 6 (6-7) CI: 95% confidence internal; Peritoneum involvement data were not available before 2018 in NCDB. Thus, IVa/b were based on 7 th Edition.