Risk of relapse and lack of benefit from adjuvant chemotherapy following surgical resection of early-stage appendiceal adenocarcinoma.

Abstract

840 Background: There are no prospective studies evaluating the benefit of adjuvant chemotherapy (AC) for patients diagnosed with early-stage Appendiceal adenocarcinoma (AA). Current NCCN guidelines suggest that AA be treated the same as colon cancer, and that 5FU-based AC should be considered if CRC-derived “high-risk” features are present. Here we evaluate the benefit of AC and identify features associated with risk of relapse in the largest study of early-stage AA to date. Methods: Foundry software (Palantir, Denver, CO) was used to query the MD Anderson (MDA) EHR to identify and extract data from all patients all AA diagnosed between 2000 and 2024. Results: Among a total of 3,662 patients with AA, 439 (12.0%) were identified as early-stage. Interestingly goblet cell histology (GCA) was most common, 176 (40%), followed by mucinous 131 (30%), enteric 117 (27%), and signet ring cell (SRC) 15 (3%); this is a notable difference from metastatic patients where GCA account for only 12.8%. In 202 patients where surgery was performed at MDA only 19 (9.4%) relapsed. As expected, 5-yr relapse incidence was higher in stage 3 vs. 2 (30% vs 9.0%, HR 3.1). GCA had a particularly low 5-yr relapse (2%), relative to mucinous (14.5%), SRC (16.7%) and enteric (20%, p=0.006). In multivariate analysis of stage 2 tumors histologic subtype (HR 5.6 mucinous, 6.6 enteric, p<0.001) and pT4 (HR 3.5, p<0.001) predicted relapse, while CRC-derived risk factors (grade, <12 LN examined, perforation, LVI, PNI) were not significant. Of 428 evaluable patients, 196 (46%) received AC. Relapse occurred in 29% with AC vs 16% without (OR 2.2, p=0.001). AC was associated with worse RFS in univariate (HR 2.1, p=0.001) but not multivariate analysis (HR 1.0, p=0.94), consistent with higher risk patients more likely to receive AC. Importantly no OS benefit was observed in the overall cohort, all stage II patients, or any subset of ‘high-risk’ stage II patients. The majority of relapse was confined to the peritoneal space (88%), and 56% of relapsed patients were candidates for complete cytoreductive surgery. This likely explains why even the majority of patients with relapse (77%) remained alive at 5 years (vs. 96% non-relapsed; HR 5.5). Conclusions: The risk of relapse following surgical resection of early-stage AA is low, particularly in GCA, and survival outcomes are favorable. We find no RFS or OS survival advantage to AC in all stage 2 patients nor in any high-risk subset. Given the lack of prospective data supporting the use of AC for patients with appendix cancer, these data suggest patients with stage 2 AA should not be offered AC.