Does the immunocytochemical detection of epithelial cells in bone marrow (micrometastasis) influence the time to biochemical relapse after radical prostatectomy?

Abstract

The detection of cytokeratin-positive bone marrow cells has been considered a prognostic factor in numerous malignant tumors. We investigated whether this was also valid for localized prostate cancer. Bone marrow aspirates were taken prior to radical prostatectomy from 169 consecutive patients with pT1/2 pN0 G1-3 adenocarcinoma of the prostate. The immunocytochemical detection of cytokeratin no. 18 (CK 18)-positive cells using monoclonal antibody CK 2 was interpreted as micrometastasis. Repeat marrow aspirations were performed at 6 months postoperatively and once a year thereafter. The patients were re-examined over a period of at least 10 and a maximum of 72 months (median 32 months). An increase in prostate specific antigen >/=0.5 ng/ml was considered a biochemical "relapse". One hundred and fifty-four patients had evaluable bone marrow aspirates, of which 74.7% were CK 18-negative and 25.3% positive. The latency period for biochemical relapse was 1481 days (median) in the CK 18-negative group and 1106 days (median) in the CK 18-positive group. This difference was not statistically significant. The CK 18-positive aspirates (n = 39) showed one positive cell in 20 cases, two positive cells in 8 and three or more positive cells in 11 cases. The preoperative number of cells had no statistically significant effect upon the onset of biochemical relapse. Only patients with three or more CK 18-positive cells tended to have a poorer prognosis. One hundred and thirteen patients had evaluable bone marrow aspirates pre- and postoperatively. Postoperative persistence or occurrence of CK 18-positive cells did not affect the outcome of the disease. The detection of CK 18-positive cells in bone marrow does not influence the prognosis of patients with localized prostate cancer within a period of 32 months (median). Solely a subgroup of patients showing a large preoperative number of CK 18-positive cells seems to tend to an unfavorable course of the disease. Thus, further studies are necessary aiming at a more detailed characterization of these cells.

Review: Biological relevance of disseminated tumor cells in cancer patients

“…16,54,118,120,141,142 These results demonstrate that DTC can reside in a prolonged latent state referred to as dormancy before IC, Iliac crest; S, significant; NS, not significant; ND, not determined; DFS, disease-free survival; DM, distant metastasis; OS, overall survival; RR, recurrance rate; RSF, recurrence-free survival; PSA, prostate specific antigen; GS, Gleason score; PE, prostatectomy; RT, radiotherapy; BS, bone scan; AD, androgen deprivation.…”

“…[175][176][177][178][179] DTC detection rates ranged between 10 and 90% (Table IV) and a comparison between the results obtained with the CK2 (anti-CK18) and the pan-CK antibody A45-B/B3 revealed a downregulation of CK18 of DTC in a significant number of cases. 148,180 There is evidence for a correlation of DTC to clinically established risk factors.…”

“…This persistence is also linked to an increased risk of late metastatic relapse. 16,54,118,141,142 For example, in high-risk breast cancer patients (>3 involved axillary lymph nodes or extensive invasion of cutaneous lymph vessels), the presence of tumor cells after therapy was associated with an extremely poor prognosis. 14 A European pooled analysis involving 696 breast cancer patients confirmed these findings.…”

Clinical Approaches to Osseous Metastases in Prostate Cancer

“…The prognostic implications of these findings are mixed. In one study of approximately 154 patients with localized disease who underwent serial biopsies, 25% of patients had CK 18 + cells in the marrow, but had an identical rate of biochemical relapse to those who did not, at a median follow-up period of 32 months [5]. The presence of such cells also appears to be unrelated to Gleason score, pretreatment PSA level, and other standard prognostic criteria [6].…”

Die klinische Bedeutung des Nachweises von isolierten Tumorzellen im Knochenmark und peripheren Blut von Patientinnen mit primärem Mammakarzinom

“…Der Einfluss dieser isolierten Tumorzellen auf das Überleben konnte bei zahlreichen soliden Tumoren wie dem Magenkarzinom [3], dem kolorektalen Karzinom [4], dem Ovarialkarzinom, dem Prostatakarzinom [5] und dem Bronchialkarzinom [6] demonstriert werden. Insbesondere vor dem Hintergrund der pathogenetisch bedeutsamen systemischen Komponente beim Mammakarzinom scheint dem Nachweis der Tumorzelldisseminierung im Knochenmark eine besondere Rolle zuzukommen [7].…”