Recurrence-free survival dynamics following adjuvant chemotherapy for resected non-colorectal cancers of the gastrointestinal tract: A systematic review of randomized controlled trials.

Abstract

e16181 Background: Adjuvant cytotoxic chemotherapies can improve recurrence-free survival (RFS) for a range of gastrointestinal malignancies. By previous systematic review of phase III randomized controlled trials (RCTs) for colorectal cancer, observed RFS improvements were driven by early divergences that occurred during active chemotherapy; late recurrence dynamics were not influenced by adjuvant therapy use. The broader applicability of this finding is not known. Methods: PubMed, Cochrane Library (CENTRAL), Embase, Scopus, and Web of Science were queried from database inception to May 16, 2024 for phase III RCTs including pancreatic, gastroesophageal, hepatocellular, and biliary tract malignancies. Trials where significant differences in RFS were observed between experimental (adjuvant chemotherapy) and control (resection alone) arms were included. Summary data were extracted from Kaplan-Meier curves using DigitizeIT, and absolute differences in RFS were compared at matched intervals (i.e., RFS event rate) using Wilcoxon matched-pairs signed rank tests. Results: A total of 3233 manuscripts were eligible for screening. After screening, 14 RCTs were selected, inclusive of periampullary (n = 4), gastroesophageal (n = 5), hepatocellular (HCC) (n = 4), and biliary tract (n = 1) carcinomas – representing 5104 patients. Across pooled RCTs, the highest rates of recurrence were observed in the first year following resection. Median RFS event rate was significantly higher with resection alone (0-0.5 years: resection alone 44.9 [IQR 14.2-84.1] vs. adjuvant chemotherapy 26.4 [IQR 7.7-41.9], p < 0.001; 0.5-1 years: resection alone 33.2 [22.7-42.1] vs. adjuvant chemotherapy 25.0 [13.8-44.5]; p = 0.007). No difference was observed during later intervals from postoperative randomization (1-2 years: p = 0.952; 2-3 years: p = 0.191; 3-4 years: p = 0.999; 4-5 years: p = 0.110). For the subset of trials where ≤6 months of adjuvant chemotherapy was used (n = 6), improvements in RFS event rates were observed only while therapy was being administered (0-0.5 years: p = 0.031). Conclusions: Across multiple gastrointestinal malignancies, improvements in RFS associated with active adjuvant chemotherapy regimens are driven by early changes in recurrence dynamics. These data may provide in vivo understanding of residual tumor cell populations after curative-intent resection and how chemotherapy can be best used to prevent recurrence. RFS event rates in the overall cohort (n=5104). Interval (years) Surgery alone (median [IQR]) Adjuvant therapy (median [IQR]) p-value 0-0.5 44.9 [14.2-84.1] 26.4 [7.7-41.9] <0.001 0.5-1 33.2 [22.7-42.1] 25.0 [13.8-44.5] 0.007 1-2 14.6 [11.7-19.1] 16.9 [10.6-21.0] 0.952 2-3 7.1 [4.1-9.6] 6.4 [4.5-7.9] 0.191 3-4 3.9 [2.5-5.0] 3.7 [1.0-5.1] 0.999 4-5 0.2 [0.0-2.2] 2.3 [0.1-3.8] 0.110