1. Impact of cytokeratin-positive cells in bone marrow on survival in patients with non-metastatic prostate cancer treated by radiotherapy PURPOSE To evaluate the clinical significance of cytokeratin- positive (CK+) cells in bone marrow aspirates (BM) prior to curatively intended external beam radiotherapy (EBRT) in patients with localized/locally advanced prostate cancer. MATERIAL AND METHODS Patients Between 1994 and 2004, 266 cT1-4pN0M0 prostate cancer patients referred to the Department of Oncology at the Radium Hospital, were screened for CK+ cells in BM. Prognostic factors All BM samples were analyzed by standardized immunocytochemical methods (ISHAGE recommendations) employing the anti-cytokeratin antibodies AE1/AE3 (fig. 1). One pathologist re- assessed Gleason score (GS) when possible (262 cases). For available needle biopsies percentage Gleason pattern 4/5 (%G4/5), percentage of positive biopsies (%PB) and percentage tumor length in all biopsies (%TL) were determined (239 cases). The prevalence of CK+ cells was compared with clinical T-category (cT1-2/cT3-4), prostate specific antigen (PSA, 7), %G4/5, %PB and %TL. Follow-up To ensure a uniform group for survival analyzes, only patients with at least one negative prognostic factor (cT3-4 or GS 7B or PSA 10 ng/ml) who had completed EBRT with or without androgen deprivation, were selected (192 patients, 5.9 years median observation time [range 0.9-10.4]). Clinical data were collected until cut-off date May 31 st,2005. Kaplan-Meier plots were generated by CK+ status with the following end-points: Overall survival (OS), cause-specific survival (CSS), distant metastases (DM) as first clinical relapse, local failure (LF) as first clinical relapse and biochemical failure (BF) defined as PSA rise of 2 ng/ml after nadir. Analyzes were also performed for a sub-group containing those who started treatment at least 5 years before cut-off (131 patients, 6.9 years median follow-up). RESULTS Of the 266 patients included, 48 (18 %) had CK+ cells in BM. Associations were found both between CK+ cells and %G4/5 (p=0.048) and GS (p=0.070), but not other prognostic factors. For the 192 patients selected for survival analyzes, the 7-years cumulative risk of DM for CK+ patients was 20 % vs. 6 % for CK- patients (p = 0.12). For the 131 patients who started treatment at least 5 years before cut-off, the 7-years cumulative risks of DM were 21 % vs. 6 % for CK+ and CK- patients respectively (p=0.069) (fig.2). The presence of CK+ cells did not have impact on BF, LF, OS or CSS in neither group. Fig. 1. Cytokeratine-positive cells in bone marrow at diagnosis of localized prostate cancer seem to predict the development of distant metastases after radiotherapy Arne Berg 1 Aasmund Berner 2 Sophie D Fosså 1,2 Wolfgang Lilleby 2 Øyvind S Bruland 1,2 Jahn M Nesland 2 Gunnar Kvalheim 2 1 University of Oslo, Norway 2 The Radium Hospital, Oslo, Norway CONCLUSION CK+ cells in bone marrow at diagnosis in non- metastatic, poor-prognosis prostate cancer, seem to be associated with the development of DM after EBRT, albeit first evident 7 years after treatment.