Impact of disseminated tumor cells in bone marrow at diagnosis in patients with nonmetastatic prostate cancer treated by definitive radiotherapy

Abstract

The purpose of this study was to explore whether detection of disseminated tumor cells (DTCs) in bone marrow (BM) of nonmetastatic prostate cancer (PC) was associated with other clinical or histopathological factors at diagnoses or clinical outcome subsequent to definitive radiotherapy (RT). We evaluated BM aspirates from 272 cT 1-4 pN 0 M 0 PC patients by immunocytochemistry employing anticytokeratin antibodies (AE1/AE3). BM-status was compared with clinical and histopathological parameters. Longterm clinical outcome was assessed in 131 of the patients who all had completed definitive RT with or without androgen deprivation (AD), initiating treatment >5 years before cut-off date June 1, 2005. They had at least 1 unfavorable prognostic feature defined as cT [3][4] or Gleason score (GS) ≥7B or PSA ≥10 lg/l. Overall death, cause-specific death, distant metastases (DM) as first clinical relapse, local failure as first clinical relapse and biochemical failure were defined as end-points. DTCs were detected in 18% of the patients and were associated with increasing GS (p 5 0.04) and percentage of Gleason pattern 4/5 (p 5 0.04). The 7-year cumulative risk of DM was 21% for BM-positive patients vs. 6% for BM-negative patients (p 5 0.07). In patients receiving RT without AD (n 5 75), the 7-year cumulative risk of DM for BM-positive patients was 28% vs. 9% for BM-negative patients (p 5 0.03). BM-status did not have impact on other end-points. In conclusion our study shows that presence of DTCs in BM at diagnosis was associated with the histological differentiation of the primary tumor and an increased risk of developing distant metastases after RT. ' 2007 Wiley-Liss, Inc.

Review: Biological relevance of disseminated tumor cells in cancer patients

“…Although a DTC-positive BM status was associated with grading and increased risk of metastasis, the study by Berg et al (2007) 181 on 266 patients did not find a correlation of DTC detection and survival. Most recently, K€ ollermann et al 179 reported on the prognostic relevance of DTC in BM found in 86/193 (44.6%) patients with clinically localized prostate cancer submitted to neoadjuvant hormonal therapy followed by radical prostatectomy and a median follow-up of 44 months.…”

“…Spread of DTC seems to be linked to histological differentiation of the primary tumor. 61,181 Moreover, while in some studies DTC detection was not associated with initial PSA concentration in the serum of prostate cancer patients, 177,179 a correlation of DTC measurement to early PSA recurrence was shown by 2 studies. 179,180 Weckermann et al 180 analyzed 82 patients and observed that the mean time to PSA increase was shorter in patients with DTC-positive compared with DTC-negative BM samples.…”

Decreased adhesiveness, resistance to anoikis and suppression of GRP94 are integral to the survival of circulating tumor cells in prostate cancer

“…CTC are thought to arise through detachment from the primary tumor, intravasation and spread to distant sites as micrometastases, which may progress to overt clinical metastases [4]. Significantly, a burst of recent evidence has revealed that CTC levels are strongly predictive of metastasis and poor disease prognosis in lung [5], breast [6], colon [7], esophageal [8], and particularly prostate cancers [9], in which the presence of detectable CTC has been correlated with advanced cancer stage in several studies [10][11][12][13]. Previous in vivo experiments from our laboratory also demonstrated that high numbers of CTC in an orthotopic mouse model of prostate cancer were associated with increased metastasis to the lung [14].…”

Prostate-specific antigen doubling time subsequent to radical prostatectomy is a predictor of outcome following salvage external beam radiation therapy: A single-centre experience

“…Berg et al have shown that patients given radical EBRT for prostate cancer with a GS of at least 4 + 3 = 7 and a positive bone marrow for CTCs have double the risk of developing biochemical recurrence [26]. Thus, it would be interesting to analyse patients with biochemical recurrence after RP for CTCs to determine whether the presence of CTCs could predict patients at risk of being resistant to salvage EBRT.…”