UroToday - Cytokeratin-positive (CK+) staining cells can be detected in the bone marrow of patients with epithelial cancers but not in control patients. In the online version of the Journal of Clinical Oncology, a group of German researchers investigated whether genetic analysis of disseminated tumor cells (DTCs) at various time points during the disease course correlates with progression and outcomes.

Between 1994 and 2002, bone marrow aspirates were obtained from 244 patients prior to radical prostatectomy. Also, bone marrow was obtained from 258 patients 6 months after radical prostatectomy (RP) and then annually until 10 years postoperatively. These samples were analyzed for CK+ cells. Among preoperative samples, 32 men were positive for at least one CK+ cell and had a significantly higher risk of biochemical relapse than patients with negative bone marrow findings. Also 32 of 244 men developed distant metastases, but these did not entirely overlap with those developing biochemical recurrence. While the presence of CK+ cells correlated with metastasis, it was not associated with local tumor relapse. Multivariate analysis revealed that DTCs in the bone marrow was an independent risk factor with a 1.73-fold increased risk for relapse (in addition to Gleason score, surgical margin status and preoperative PSA). DTCs in the bone marrow were also a strong predictor for metastasis with a 2.87-fold increased risk. These patients tended to develop biochemical recurrence during the first 2 years and metastasis during the first 4 years of clinical follow-up. For metastasis-free survival within 48 months, CK-positive statis was the most important risk factor.

Regarding DTC evaluation in post-prostatectomy samples, 214 men had 656 aspirates available for testing. There was no significant influence of positive postoperative samples on outcome for recurrence-free survival. There was also no correlation between a conversion from negative preoperative aspirate to positive postoperative aspirate and progression. Thus, detection of CK+ cells before surgery is more prognostic than detection during follow-up. Comparative genomic hybridization was performed to examine for genomic alterations. DTCs from patients with metastasis had on average 11.4 alterations, compared with 7.1 for primary tumors. Analysis of matched pairs from primary tumors of patients with and without bone metastasis support that intratumoral genetic progression is not likely occurring, rather that chromosomal aberrations needed for metastatic growth are selected at the metastatic site.

Weckermann D, Polzer B, Ragg T, Blana A, Schlimok G, Arnholdt H, Bertz S, Harzmann R, Klein CA
J Clin Oncol. 2009 Feb 23. Epub ahead of print.
doi:10.1200/JCO.2008.17.0563

UroToday Contributing Editor Christopher P. Evans, MD, FACS

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