Intersection of Black race and carbohydrate antigen 19-9 nonproduction underpins worse pathologic response to neoadjuvant therapy in pancreatic cancer.

BACKGROUND: Black patients with pancreatic ductal adenocarcinoma (PDAC) are less likely to have a major pathologic response (MPR) after neoadjuvant chemotherapy (NAC). Data suggest lower baseline carbohydrate antigen 19-9 (CA 19-9) among Black patients. Whether CA 19-9 nonproduction contributes to racial differences in NAC response was evaluated, and the biological mechanisms underlying the reduced response in CA 19-9 nonproducers (CAnonprod) were investigated. METHODS: Black and White patients with PDAC who received ≥2 NAC cycles and pancreatectomy at seven centers were reviewed. Patients were categorized as CA 19-9 producers (CAprod; CA 19-9 > 5 U/mL) or CAnonprod (CA 19-9 ≤ 5 U/mL). Univariable and multivariable models assessed CAnonprod rates by race and the association of CAnonprod with MPR. The Pancreatic Cancer Action Network's SPARK platform was queried for genomic data. Differentially mutated genes were identified by Fisher exact test; differentially expressed gene analysis used an absolute fold change of ≥2 and an adjusted p value of <.05. RESULTS: Among 415 patients (385 CAprod and 30 CAnonprod), Black patients comprised more CAnonprod than CAprod (50% vs. 13%; p < .01). MPR rates were lower among CAnonprod versus CAprod (8% vs. 26%; p = .03). CA nonproduction was associated with decreased odds of an MPR (odds ratio [OR], 0.21; 95% CI, 0.04-0.99), and Black race was associated with increased odds of CA 19-9 nonproduction (OR, 8.7; 95% CI, 3.8-19.7). CAnonprod had higher rates of SWI/SNF alterations than CAprod (52% vs. 34%; p < .01; p-adjusted, not significant). LIPF was downregulated and CTCFL was upregulated in CAnonprod. CONCLUSIONS: CA 19-9 nonproduction is more prevalent in Black patients, and potentially mediates lower rates of MPR. CAnonprod have a distinct molecular profile, which suggests a biological basis for racial differences in chemoresponsivity.