Risk of Relapse and Efficacy of Adjuvant Chemotherapy in Localized Appendiceal Adenocarcinoma

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Importance: Relapse risk and benefit of adjuvant chemotherapy after resection of appendiceal adenocarcinoma (AA) are uncertain. Objective: To identify clinicopathologic and genomic factors associated with relapse and assess efficacy of adjuvant chemotherapy in localized AA. Design, Setting, and Participants: This retrospective cohort study (January 2000 through February 2024; median follow-up, 62.6 months) used Kaplan-Meier and Cox proportional hazards modeling. It took place at the University of Texas MD (UT MD) Anderson Cancer Center with validation from Memorial Sloan Kettering Cancer Center (MSKCC). Participants included a complete localized cohort of 439 patients with stage I to III AA from UT MD Anderson, of whom 202 underwent surgery at UT MD Anderson and also included a validation cohort of 128 patients with stage II AA from MSKCC. Exposures: Surgical resection with or without adjuvant chemotherapy. Main Outcomes and Measures: Rate of recurrence, recurrence-free survival (RFS), and overall survival (OS). Results: There were 439 patients with localized AA (median age, 56.5 [IQR, 22.2-83.7] years; 50% female and 50% male) managed at MD Anderson between January 2000 and February 2024. Of 202 MDA surgical patients, 19 (9.4%) had a relapse including 9 (6%) patients with stage II and 8 (19.5%) of patients stage III disease. Five-year OS was 95.7% without vs 77.2% with relapse (hazard ratio [HR], 5.50; 95% CI, 3.07-9.83; P < .001). Relative to goblet cell tumors, mucinous (HR, 5.60; 95% CI, 2.1-15; P < .001) and enteric-type (HR, 6.60; 95% CI, 2.9-15; P < .001) histologies were independently associated with relapse, as was pathologic T4 (HR, 3.30; 95% CI, 1.9-5.7; P < .001). Importantly, poor differentiation, perforation, lymphovascular invasion, and perineural invasion, known risk factors in colorectal cancer, were not significantly associated with relapse. For the complete localized cohort, adjuvant chemotherapy was not associated with improved RFS (univariate HR, 2.06; 95% CI, 1.36-3.13; P = .001 and multivariable HR, 0.98; 95% CI, 0.43-2.28; P = .90) or OS (univariate HR, 1.80; 95% CI, 1.0-3.2; P = .04 and multivariable HR, 0.71; 95% CI, 0.24-2.1; P = .53). TP53 mutation in goblet cell tumors (HR, 6.93; 95% CI, 1.50-31.00; P = .01) and GNAS mutation in nongoblet tumors (HR, 17.0; 95% CI, 3.09-93.3; P = .001) were associated with greater risk of relapse. Conclusions and Relevance: These results demonstrate that relapse after resection of localized AA is uncommon. Molecular profiling and histopathologic subtype refine risk. Adjuvant chemotherapy were not associated with benefit.

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