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

被引:34
作者
Berg, Arne
Berner, Aasmund
Lilleby, Wolfgang
Bruland, Oyvind S.
Fossa, Sophie D.
Nesland, Jahn M.
Kvalheim, Gunnar
机构
[1] Univ Oslo, Fac Med, Oslo, Norway
[2] Natl Hosp Norway, Radium Hosp Med Ctr, Dept Pathol, Oslo, Norway
[3] Natl Hosp Norway, Radiumhosp Med Ctr, Dept Med Oncol & Radiotherapy, Oslo, Norway
关键词
prostate cancer; minimal residual disease; immunochemistry; bone marrow; radiotherapy;
D O I
10.1002/ijc.22488
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 mu g/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 = 0.04) and percentage of Gleason pattern 415 (p = 0.04). The 7-year cumulative risk of DM was 21% for BM-positive patients vs. 6% for BM-negative patients (p = 0.07). In patients receiving RT without AD (n = 75), the 7-year cumulative risk of DM for BM-positive patients was 28% vs. 9% for BM-negative patients (p = 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. (c) 2007 Wiley-Liss, Inc.
引用
收藏
页码:1603 / 1609
页数:7
相关论文
共 49 条
[1]   Therapeutic implications of cancer stem cells [J].
Al-Hajj, M ;
Becker, MW ;
Wichal, M ;
Weissman, I ;
Clarke, MF .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2004, 14 (01) :43-47
[2]   Proliferation of prostate cancer cells in the bone marrow predicts recurrence in patients with localized prostate cancer [J].
Bianco, FJ ;
Wood, DP ;
de Oliveira, JG ;
Nemeth, JA ;
Beaman, AA ;
Cher, ML .
PROSTATE, 2001, 49 (04) :235-242
[3]   Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial [J].
Bolla, M ;
Collette, L ;
Blank, L ;
Warde, P ;
Dubois, JB ;
Mirimanoff, RO ;
Storme, G ;
Bernier, J ;
Kuten, A ;
Sternberg, C ;
Mattelaer, J ;
Torecilla, JL ;
Pfeffer, JR ;
Cutajar, CL ;
Zurlo, A ;
Pierart, M .
LANCET, 2002, 360 (9327) :103-108
[4]   Standardization of the immunocytochemical detection of cancer cells in BM and blood: I. establishment of objective criteria for the evaluation of immunostained cells [J].
Borgen, E ;
Naume, B ;
Nesland, JM ;
Kvalheim, G ;
Beiske, K ;
Fodstad, O ;
Diel, I ;
Solomayer, EF ;
Theocharous, P ;
Coombes, RC ;
Smith, BM ;
Wunder, E ;
Marolleau, JP ;
Garcia, J ;
Pantel, K .
CYTOTHERAPY, 1999, 1 (05) :377-388
[5]  
Borgen E, 1998, J PATHOL, V185, P427, DOI 10.1002/(SICI)1096-9896(199808)185:4<427::AID-PATH127>3.0.CO
[6]  
2-7
[7]   A pooled analysis of bone marrow micrometastasis in breast cancer [J].
Braun, S ;
Vogl, FD ;
Naume, B ;
Janni, W ;
Osborne, MP ;
Coombes, RC ;
Schlimok, G ;
Diel, IJ ;
Gerber, B ;
Gebauer, G ;
Pierga, JY ;
Marth, C ;
Oruzio, D ;
Wiedswang, G ;
Solomayer, EF ;
Kundt, G ;
Strobl, B ;
Fehm, T ;
Wong, GYC ;
Bliss, J ;
Vincent-Salomon, A ;
Pantel, K .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (08) :793-802
[8]   Hematogenous micrometastases in osteosarcoma patients [J].
Bruland, OS ;
Hoifodt, H ;
Sæter, G ;
Smeland, S ;
Fodstad, O .
CLINICAL CANCER RESEARCH, 2005, 11 (13) :4666-4673
[9]   Defining biochemical failure after radiotherapy with and without androgen deprivation for prostate cancer [J].
Buyyounouski, MK ;
Hanlon, AL ;
Eisenberg, DF ;
Horwitz, EM ;
Feigenberg, SJ ;
Uzzo, RG ;
Pollack, A .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2005, 63 (05) :1455-1462
[10]  
Cher ML, 1999, CLIN CANCER RES, V5, P2421