title: Presence of bone marrow micro-metastases in stage I-III colon cancer patients is associated with worse disease-free and overall survival.
abstract: The prognostic significance of bone marrow micro-metastases (BMM) in colon cancer patients remains unclear. We conducted a prospective cohort study with long-term follow-up to evaluate the relevance of BMM as a prognostic factor for disease free (DFS) and overall survival (OS) in stage I-III colon cancer patients. In this prospective multicenter cohort study 144 stage I-III colon cancer patients underwent bone marrow aspiration from both iliac crests prior to open oncologic resection. The bone marrow aspirates were stained with the pancytokeratin antibody A45-B/B3 and analyzed for the presence of epithelial tumor cells. DFS and OS were analyzed using a Cox proportional hazard model and robust standard errors to account for clustering in the multicenter setting. Median overall follow-up was 6.2 years with no losses to follow-up, and 7.3 years in patients who survived. BMM were found in 55 (38%) patients. In total, 30 (21%) patients had disease recurrence and 56 (39%) patients died. After adjusting for known prognostic factors, BMM positive patients had a significantly worse DFS (hazard ratio [HR] 1.33; 95% confidence interval [95% CI]: 1.02-1.73; P = 0.037) and OS (HR 1.30; 95% CI: 1.09-1.55; P = 0.003) compared to BMM negative patients. Bone marrow micro-metastases occur in over one third of stage I-III colon cancer patients and are a significant, independent negative prognostic factor for DFS and OS. Future trials should evaluate whether node-negative colon cancer patients with BMM benefit from adjuvant chemotherapy.
authors.affiliation: Department of Surgery, Hospital Center Biel, Biel/Bienne, Switzerland.|Department of Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Carsten T
authors.initials: CT
authors.lastname: Viehl
authors.affiliation: Department of Surgery, University Hospital Basel, Basel, Switzerland.|Department of Surgery, Cantonal Hospital Olten, Olten, Switzerland.
authors.forename: Benjamin
authors.identifier: http://orcid.org/0000-0002-3652-4792
authors.initials: B
authors.lastname: Weixler
authors.affiliation: Department of Oncology/Hematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.|University Clinic for Visceral Surgery and Medicine, Inselspital Berne, University of Berne, Berne, Switzerland.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Guller
authors.affiliation: Department of Surgery, University Hospital Basel, Basel, Switzerland.|Basel Institute for Clinical Epidemiology and Biostatistics ceb, University Hospital Basel, Basel, Switzerland.
authors.forename: Salome
authors.initials: S
authors.lastname: Dell-Kuster
authors.affiliation: Department of Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Rachel
authors.initials: R
authors.lastname: Rosenthal
authors.affiliation: Department of Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Michaela
authors.initials: M
authors.lastname: Ramser
authors.affiliation: University Clinic for Visceral Surgery and Medicine, Inselspital Berne, University of Berne, Berne, Switzerland.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Banz
authors.affiliation: Department of Surgery, Lindenhof Hospital, Berne, Switzerland.
authors.forename: Igor
authors.initials: I
authors.lastname: Langer
authors.affiliation: Department of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.affiliation: Department of Pathology, University Hospital Basel, Basel, Switzerland.|Department of Pathology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Department of Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Oertli
authors.affiliation: Department of Surgery, Cantonal Hospital Olten, Olten, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Zuber
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019046:Bone Marrow Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000556:secondary*; D003110:Colonic Neoplasms / Q000401:mortality* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D061206:Neoplasm Micrometastasis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000401:mortality; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis
keywords: Bone marrow; colon cancer; micro-metastases; prognosis