Session: Sarcoma, Colorectal and Upper GI/Thoracic Virtual Poster Grand Rounds
V21: Challenging the Theory of a Chronological Lymphatic-hematologic Tumor Cell Spread - The Simultaneous Presence of Isolated Tumor Cells and Bone Marrow Micrometastases in Stage I & II Colon Cancer
Attending Surgeon University Hospital Zurich, Department of General-, HPB- and Transplantation Surgery Zürich, Switzerland
Disclosure: Disclosure information not submitted.
Participants should be aware of the following financial/non-financial relationships:
Michaela Ramser: Disclosure information not submitted.
Introduction: According to the current doctrine, tumor progression is a chronological process that begins with lymphatic invasion. Therefore, the significance of bone marrow micrometastases (BMM) in patients with lymph node-negative colon cancer (CC) is unclear. This study investigates the relationship of isolated tumor cells (ITC) in sentinel lymph nodes (SLN) and BMM in patients in early CC.
Methods: During oncological resection in patients with stage I&II CC, BM was aspirated from both iliac crests and in vivo SLN mapping was performed. Stainings were done with pancytokeratin markers (A45-B/B3 and AE1/AE3) as well as H&E. The correlation between the occurrence of ITC+ and BMM+ and their impact on survival was assessed using Cox regression analysis.
Results: In a total of 78 patients with stage I&II CC, 11 patients (14%) were ITC+, 29 patients (37%) BMM+. Of these patients, only two demonstrated simultaneous ITC+/BMM+. The occurrence of BMM+ was neither associated with ITC+ in standard correlation (kappa=-0.13 [95% confidence interval [CI]=-0.4-0.14], p=0.342) nor univariate (odds ratio [OR]=0.39, 95%CI:0.07-1.50, p=0.180) or multivariate (OR=0.58, 95%CI:0.09-2.95, p=0.519) analysis. Neither ITC+ alone (n=11) vs. ITC- (n=67) nor BMM+ (n=29) vs. BMM- (n=49) did influence overall (OS), disease-specific or recurrence-free survival (RFS). The combined detection of ITC+/BMM+ demonstrated the OS (HR=61.60, 95%CI:17.69-214.52, p=0.032) and RFS (HR=61.60, 95%CI:17.69-214.5, p=0.032).
Conclusions: Our results indicate that the simultaneous and not interdependent presence of very early lymphatic and hematologic tumor cell spread may be considered as a relevant prognostic risk factor for patients with stage I&II CC. The results thus challenge the prevailing theory of sequential tumor progression and suggest that common assumptions about tumor spread may need to be reconsidered. The results highlight the importance of a thorough analysis and evaluation of additional risk factors in colon cancer patients such as ITC in SLN and tumor cells in BM.
Learning Objectives:
name pathways of tumor cell spread in early colon cancer
explain the controversy of simultaneous versus sequential tumor progression
recognize the importance of sentinel lymph node mapping and immunostainings as well as bone marrow examination in patients with colon cancer