Piritramide analgesia reduces CEA mRNA-positive circulating tumor cells' presence compared to morphine and epidural analgesia following radical colon cancer surgery

Purpose: Piritramide is a strong opioid widely used for postoperative analgesia (PA) in Europe while morphine and epidural PA are well established worldwide. Our retrospective analysis revealed that compared to morphine, piritramide improved cancer-specific survival in patients undergoing radical colon cancer surgery. Since circulating tumor cells’ (CTCs) presence has negative effect on colon cancer survival, we hypothesized that different types of PA could affect postoperative CTCs levels. Patients and Methods: In total, 60 patients undergoing radical colon cancer surgery were enrolled in this prospective, randomized, two-center pilot study. Patients were randomized to receive either piritramide, morphine, or epidural PA. The presence of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20) mRNA positive CTCs in peripheral blood was measured at four points (before and immediately after surgery, on postoperative day 2, and one month after surgery) using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). Perioperative treatment was standardized. Results: In piritramide-treated patients, the levels of CEA mRNA positive cells were significantly lower on postoperative day 2 compared to other patients (p=0.04). CK-20 mRNA positive cells levels remained similar. In all groups, CTCs levels returned to preoperative baseline one month after surgery. Groups were similar regarding age, sex, ASA status, TNM, and grading. Conclusion: Compared to morphine and epidural analgesia, piritramide reduces postoperative CEA mRNA-positive circulating tumor cells’ presence following radical colon cancer surgery. Further trials enrolling larger numbers of patients are needed. Acknowledgments: This study was supported by Ministry of Health of the Czech Republic (NV18-03-00470), Ministry of Education, Youth and Sport of the Czech Republic (LO1304, LM2015089), European Regional Development Fund (ENOCH CZ.02.1.01/0.0/0.0/16_019/0000868) and Cancer Research Czech Republic. Citation Format: Josef Srovnal, Emil Berta, Alona Rehulkova, Monika Vidlarova, Petr Prasil, Lubomir Vecera, Petr Stourac, Pavla Kourilova, Marian Hajduch. Piritramide analgesia reduces CEA mRNA-positive circulating tumor cells’ presence compared to morphine and epidural analgesia following radical colon cancer surgery [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B41.