Clinical impact of disseminated tumor cells in patients with non-metastatic prostate cancer treated by definitive radiotherapy

4575 Background: Detection of disseminated tumor cells (DTCs) in bone marrow (BM) has been proven to be an independent prognostic factor in breast cancer. To our knowledge, we here present the first larger study of radically treated prostate cancer (PC) with sufficiently long-term follow-up where the association between DTCs at diagnosis and clinical outcome has been studied. Methods: We screened 272 cT1–4pN0M0 PC patients for DTCs in BM-aspirates between 1994 and 2004. Monoclonal antibodies against cytokeratins (AE1/AE3) and standardized immunocytochemical methods were applied for detection. BM-status was compared with clinical and histopathological factors at diagnosis in all patients and with long-term clinical outcome in 131 patients. They all started treatment including definitive radiotherapy (RT) before June, 2000 and had a relatively poor prognosis defined as cT3–4 or Gleason score (GS) ≥ 7B (4 + 3) or PSA ≥ 10 μg/l. Kaplan-Meier plots were generated by BM-status with the following end-points: Overall death, cause-specific death, distant metastases (DM) as first clinical relapse, local failure as first clinical relapse and biochemical failure. Results: DTCs were detected in 18% of the patients and were significantly associated with increasing percentage Gleason grade 4/5 (p = .035, Mann-Whitney) but not with dichotomized GS, tumor-stage or PSA. In the follow-up cohort (median observation time 6.9 years), the 7-year cumulative risk of DM was 21% in BM-positive patients vs. 6% in BM-negative patients (p = .069, log rank). No association was found between DTCs and other end-points. A sub-group analysis of 73 patients with GS ≥ 7B yielded a 34% 7-year cumulative risk of DM in BM-positive patients vs. 10% in BM-negative patients (p = .039, log rank). DTCs did not predict DM in 55 patients with GS ≤ 7A (3 + 4). In a multivariate analysis, dichotomized GS (RR = 7.8 [95% confidence interval (CI) = 1.0–60.7], p = .049) and BM-status (RR = 3.0 [95% CI = .9–9.4], p = .066) had independent impact on DM. Conclusions: The presence of DTCs in BM at diagnosis of non-metastatic PC is associated with the histological differentiation of the primary tumor and seems to predict development of DM after definitive RT. No significant financial relationships to disclose.