Antibiotic treatment and survival in patients with resected, early-stage pancreatic ductal adenocarcinoma receiving chemotherapy.

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is a clinically challenging malignancy, largely due to chemoresistance. Bacteria within the PDAC microbiome may mediate chemoresistance, suggesting that alteration of the microbiome with antibiotics could improve chemotherapy response.

Methods: We utilized the SEER-Medicare database to select patients with resected, early-stage PDAC diagnosed between 2007 and 2017. The primary outcome of this study was overall survival (OS). Receipt of antibiotic treatment within one month after adjuvant chemotherapy initiation was determined from Medicare claims data. Propensity scores (PSs) were used to match patients who received antibiotics with patients who did not receive antibiotics. The Kaplan-Meier method was used to calculate 5-year OS rates, and cox regression analysis was used to assess association between receiving antibiotics and OS. All hypotheses were 2-sided.

Results: Of the 712 patients with resected, early-stage PDAC, 629 (88.3%) were treated with adjuvant gemcitabine and 177 (24.9%) received antibiotics in the one month following chemotherapy initiation. The mean (SD) age at diagnosis was 73.7 (5.1) years and patients were mostly women, White, and from metropolitan areas in the northeastern or western US. A total of 143 PS-matched pairs were evaluated. Among patients treated with gemcitabine, antibiotic treatment was associated with a 37% improvement in OS and a 30% improvement in cancer-specific survival.

Conclusions: Antibiotic treatment in the one month following adjuvant gemcitabine initiation was associated with improved survival. These findings provide additional support for the hypothesis that antibiotic treatment may alter the pancreatic microbiome in a manner that reduces chemoresistance, potentially improving PDAC outcomes.