Small nodal tumor infiltrates (SNTI; isolated tumor cells and
micrometastases) in sentinel lymph nodes and bone marrow
micrometastases (BMM) were independently described as prognostic
factors in patients with colon cancer.
To examine the association between the occurrence of SNTI and BMM as
well as their prognostic relevance.
Design, Setting, and Participants
This prospective study was conducted at 3 university-affiliated
institutions in Switzerland between May 2000 and December 2006.
Statistical analyses were performed in October 2016. A total of 122
patients with stage I to III colon cancer were included. Follow-up
time exceeded 6 years, with no patients lost to follow-up.
Bone marrow aspiration from the iliac crests and in vivo sentinel
lymph node mapping were performed during open standard oncological
resection. Bone marrow aspirates were stained with the
pancytokeratin marker A45-B/B3. All sentinel lymph nodes underwent
multilevel sectioning and were stained with hematoxylin-eosin and
the pancytokeratin marker AE1/AE3.
Main Outcomes and Measures
Association of SNTI in sentinel lymph nodes and BMM in patients with
stage I to III colon cancer and the prognostic effect on
disease-free survival (DFS) and overall survival (OS).
Of the 122 patients, 63 (51.6%) were female, with a mean (SD) age of
71.2 (11.7) years. Small nodal tumor infiltrates and BMM were found
in a total of 21 patients (17.2%) and 46 patients (37.7%),
respectively. The occurrence of BMM was not associated with the
presence of SNTI by standard correlation (κ, -0.07; 95% CI,
-0.29 to 0.14; P = .49) nor by univariate logistic
regression analysis (odds ratio, 0.64; 95% CI, 0.22-1.67;
P = .37) or multivariate logistic regression analysis
(odds ratio, 1.09; 95% CI, 0.34-3.28; P = .88). The
presence of SNTI was an independent negative prognostic factor for
DFS (hazard ratio [HR], 2.93; 95% CI, 1.24-6.93;
P = .02) and OS (HR, 4.04; 95% CI, 1.56-10.45;
P = .005), as was BMM (HR, 2.07; 95% CI, 1.06-4.06;
P = .04; and HR, 2.68; 95% CI, 1.26-5.70;
P = .01; respectively). The combined detection of BMM
and SNTI demonstrated the poorest DFS (HR, 6.73; 95% CI, 2.29-19.76;
P = .006) and OS (HR, 5.96; 95% CI, 1.66-21.49;
P = .03).
Conclusions and Relevance
This study demonstrates no association between the occurrence of
SNTI and BMM in patients with stage I to III colon cancer. However,
both SNTI and BMM are independent negative prognostic factors
regarding DFS and OS, and the occurrence of both is associated with
significantly worse prognosis compared with either one of them.
clinicaltrials.gov Identifier: NCT00826579.